Vascular variations encountered during laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer: a retrospective cohort study.

Laparoscopic surgery for cancer located in the transverse colon or splenic flexure is difficult because of vascular variability in this region and adjacent vital organs such as the pancreas, spleen, and duodenum. This retrospective cohort study involved 51 patients who underwent laparoscopic surgery for colon cancer at Tokushima University Hospital from July 2015 to December 2020. Variations of the middle colic artery (MCA), left colic artery (LCA), middle colic vein (MCV), and first jejunal vein (FJV) and short-term outcomes of laparoscopic surgery in patients with each vascular variation were evaluated. Variations of the MCA, LCA, MCV, and FJV were classified into four, three, five, and three patterns, respectively. The short-term outcomes of laparoscopic surgery for transverse colon cancer in patients with MCA variations and those with FJV variations were evaluated, and no significant difference was found in the operation time, blood loss, postoperative complication rate, time from surgery to start of dietary intake, or time from surgery to discharge among the different variations. Additionally, no significant differences were found in the short-term outcomes of laparoscopic surgery for descending colon cancer in patients with LCA variations. Preoperative assessment of vascular variations may contribute to the stability of short-term outcomes of laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer.


Blue light irradiation inhibits the growth of colon cancer and activation of cancer-associated fibroblasts.

Irradiation with a specific wavelength of light using light-emitting diodes (LEDs) has various effects on cells and organisms. Recently, the antitumor effects of visible blue light on tumor cells were reported; however, the mechanism and effects on the tumor microenvironment remain unclear. Human colon cancer cells (HCT-116) were injected into the rectal wall of nude mice. Tumors were irradiated with a 465-nm LED light at 30 mW/cm for 30 min. Tumor volumes and the expression levels of opsin 3 (Opn3), autophagy-related factors, cancer-associated fibroblast (CAF) markers, and programmed cell death 1-ligand (PD-L1) were measured. Additionally, human intestinal fibroblasts were cultured in HCT116-conditioned medium (CM) to prepare CAFs. CAFs were divided into an LED group and a control group, and the effect of the LED light on CAF activation in colon cancer cells was examined. Irradiation with blue LED light suppressed tumor growth; Opn3 expression was localized to the cell membrane in the LED group. Irradiated tumors exhibited increased autophagy-related gene expression. Furthermore, in the LED group, TGF-β and α-SMA expression levels in the fibroblasts were decreased. Regarding CAFs, α-SMA and IL-6 expression levels were decreased in the LED group. HCT-116 cells cultured in CAF-CM with LED irradiation showed no enhanced migration or invasion. In the HCT-116 cells cultured in CM of CAFs irradiated with LED, the relative increase in PD-L1 expression was lower than that noted in the CAF-CM without LED irradiation. Blue LED light may have a direct antitumor effect on colon cancer and also an inhibitory effect on CAFs.


Risk factors for postoperative ileus after diverting loop ileostomy closure.

Postoperative ileus is one of the most common complications after diverting loop ileostomy closure. Some reports have investigated the risk factors for postoperative complications or ileus after ileostomy closure; however, these studies did not evaluate the index surgery sufficiently. In this study, we evaluated the risk factors, including the details of the index surgery, for ileus after diverting ileostomy closure. This was a retrospective study of patients who underwent ileostomy closure following index surgery for rectal cancer. Patients who developed postoperative ileus [POI (+)] and patients who did not [POI (-)] after ileostomy closure were compared. Sixty-eight patients were evaluated and were divided into two groups: POI (+) (n = 11) and POI (-) (n = 57), and the groups were compared. There were no significant differences in the details of the index surgery, operative procedure, transanal total mesorectal excision, lateral lymph node dissection, operating time, or blood loss. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery were significantly higher in the POI (+) group. The incidence of Clavien-Dindo grade ≥ III complications and adjuvant chemotherapy after index surgery may increase the risk of postoperative ileus after ileostomy closure.


【外科代謝栄養と東洋医学:漢方による周術期管理へのサポート】大建中湯による周術期管理のサポート

近年では漢方の分子生物学的な作用機序の解明が進み，臨床においても質の高いランダム化比較試験により漢方の有用性が明らかになってきた．現在では大建中湯を含む多くの漢方製剤が広く臨床の現場で用いられている．大建中湯は乾姜，人参，山椒の3つの生薬に膠飴を加えた漢方で，外科領域においては癒着性イレウスや麻痺性イレウス，過敏性腸症候群，クローン病などを適応とし，消化管運動促進作用，腸管血流増加作用，抗炎症作用などが報告されている．近年では，食道・胃・大腸・肝臓・膵臓・肝移植外科それぞれの領域でランダム化試験が実施され，大建中湯の周術期管理における有効性が証明されている．また分子生物学的なメカニズムについても解明がすすみ，現在，大建中湯は消化管外科・肝胆膵外科の分野を問わず消化器外科全般における周術期管理のkey drugとして位置付けられている．本稿では消化器外科領域における大建中湯による周術期管理のサポートについて概説する．(著者抄録)

The Japanese Journal of Surgical Metabolism and Nutrition


The correlation of immunoscore and frailty in colorectal cancer.

The Immunoscore is a useful prognostic and predictive factor for colorectal cancer. Frailty predicts overall and recurrence-free survival following resection of colorectal cancer, and the immunosuppressive state of frailty might affect tumor progression. This study investigated the relationship between the Immunoscore and frailty in colorectal cancer. This retrospective study included patients who underwent radical surgery for stage II and III colorectal cancer (n = 108). Patients were divided into frail (n = 11) and non-frail (n = 97) groups, and low (IS0-2) (n = 70) and high (IS3-4) Immunoscore groups (n = 38), for comparison. American Society of Anesthesiologists physical status was higher, tumor diameter was larger, number of well-differentiated tumors was higher, albumin was lower, 5-year overall survival (OS) was lower (frail group: 50.0%, non-frail group: 90.5%, p < 0.001) and 5-year disease-free survival (DFS) was lower (frail group: 36.4%, non-frail group: 75.2%, p = 0.024) in the frail than in the non-frail group. Left colon cancer was more, 5-year OS was lower (IS0-2 group: 82.0%, IS3-4 group: 96.7%, p = 0.040) and 5-year DFS was lower (IS0-2 group: 66.3%, IS3-4 group: 83.3%, p = 0.043) in the IS0-2 than in the IS3-4 group. The Immunoscore was lower in the frail than in the non-frail group. Immunoscore and frailty are prognostic and predictive factors in colorectal cancer, and they are correlated with each other. The immunosuppressive state from frailty might affect this correlation.

International Journal of Clinical Oncology


Epigallocatechin-3-gallate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancerssociated fibroblasts.

In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancerssociated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin 3allate (EGCG) exerts antiumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through coulture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells . EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumorromoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumorromoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of antiancer therapy.


Usefulness of a stepwise training program for laparoscopic gastrectomy.

Laparoscopic gastrectomy (LG) is a complicated procedure with a long learning curve. This study was performed to investigate the usefulness of our stepwise training program for LG for improving the quality of the surgery. The stepwise training method comprised the following four steps: (1) basic training using a dry box and checking by mentors; (2) advanced training, including the use of animals and cadavers; (3) clinical experience, including standardization and preoperative three-dimensional simulation; and (4) self-assessment and feedback. In total, 153 patients who underwent curative gastrectomy for gastric cancer were included in this study. The operative time gradually decreased for both laparoscopic distal gastrectomy (LDG) (2013, 395inutes; 2017, 278inutes; P < .001; = -0.68) and laparoscopic total gastrectomy (LTG) (2013, 476inutes; 2017, 319inutes; P < .001; = -0.56). The blood loss volume gradually decreased for both LDG (2013, 43.0 mL; 2017, 18.6 mL; P < .005; = -0.30) and LTG (2013, 143.8 mL; 2017, 13.5 mL; P < .005; = -0.41). Our stepwise training program contributes to reduce operation time and blood loss in LG.


Strategy for laparoscopic repair of inguinal hernia after robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is nowadays being performed worldwide, and inguinal hernia (IH) continues to be a common complication of radical prostatectomy. Laparoscopic repair of IH is often difficult via internal dissection because of adhesion of the preperitoneal cavity. This study aimed to categorize the intraoperative condition of, and devise a strategy for, IH after RARP. Of 577 patients who underwent RARP, 18 developed IH. These 18 patients then underwent laparoscopic IH repair using the transabdominal preperitoneal approach (TAPP) or modified intraperitoneal onlay mesh repair (mIPOM). Internal dissection was categorized into two groups according to the appearance of Cooper's ligament (exposed or not exposed). After RARP, four patients had exposure of Cooper's ligament while 14 patients showed no exposure. Both patients in the exposed group underwent TAPP and all patients in the not-exposed group underwent mIPOM. There was no significant difference between normal TAPP and RARP regarding operative factors, and IH recurrence was not observed. Laparoscopic repair of IH after RARP is rendered safe and efficient by using our categorization based on the exposure of Cooper's ligament and extension of preperitoneal space.


A "diversity and inclusion" lecture for promoting self-awareness among medical students.

The concept of 'diversity and inclusion' is being adopted worldwide, but it is not yet understood well in Japan. We conducted this study to evaluate the impact of a lecture aimed at increasing awareness of academic careers and the benefits of having diversity and inclusion. Two female surgeons delivered a 120-min lecture on "diversity and inclusion" to third-year medical students at Tokushima University. To assess the impact of the lecture, a questionnaire was distributed, for participants to complete anonymously before and after the lecture. Eighty-two students participated in the study (39 men, 38 women, and 5 unknown). Based on the questionnaire responses, 57.1% of the students had already perceived inequality in conduct because of gender. A comparison of pre- and post-lecture responses revealed a significant increase in confidence to succeed in their medical career (56.5% vs. 77.5%, p < 0.01). Learners were more likely to believe that gender would not become a barrier to career development (42.4% vs. 66.7%, p < 0.01). Moreover, 90.4% of the students felt positively about a career in surgery following the lecture. The lecture promoted awareness about diversity, self-awareness, and career development and motivated students to consider specializing in surgery later in their career.


Propensity Score-Matched Analysis of the Short- and Long-Term Outcomes of Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer.

Robotic gastrectomy (RG) has been rapidly adopted for gastric cancer (GC) treatment. However, the benefits of RG over laparoscopic gastrectomy (LG) for GC remain unclear. A total of 451 patients who underwent either RG (n = 83) or LG (n = 368) for GC were enrolled in this study. A 1:1 matched, propensity score-matched analysis was performed using the following factors: age, sex, body mass index, pT, pN, pStage, tumor location, vessel invasion, tumor markers, surgical procedure, reconstruction method, extent of lymphadenectomy, and Endoscopic Surgical Skill Qualification System qualified surgeon as an operator. The surgical outcomes of the two groups were compared. A well-balanced cohort of 158 patients was analyzed (n = 79 in the RG group, n = 79 in the LG group). Regarding the short-term outcomes, the respective blood loss volume, drain amylase content, and number of retrieved lymph nodes in the RG and LG groups were 38.62 ± 73.06 ml and 67.53 ± 108.20 ml (p < 0.05), 450 ± 371 IU/l and 1590 ± 6392 IU/l (p < 0.01), and 35.02 ± 15.51 and 25.28 ± 11.70 (p < 0.01). The morbidity rate was similar between the RG and LG groups (not significant [NS]). Regarding the long-term survival outcomes, there were no intergroup differences in 3-year overall survival (91.72% in the RG group vs. 83.39% in the LG group: NS) and 3-year, disease-free survival (93.31% in the vs. 90.44%: NS). RG was safe and contributed to better short-term outcomes and similar long-term survival outcomes compared with LG.


ASO Author Reflections: The Role of Robotic Gastrectomy for Gastric Cancer.


Short-term outcomes of laparoscopic / robotic gastrectomy compared with open gastrectomy for advanced gastric cancer following chemotherapy.

Purpose : This study aimed to investigate the short-term outcomes of laparoscopic gastrectomy / robotic gastrectomy after chemotherapy in patients with advanced gastric cancer and compare these outcomes with those of open gastrectomy. Methods : Fifty patients who underwent radical gastrectomy for advanced gastric cancer after chemotherapy between 2007 and 2021 were retrospectively analyzed. The patients were divided into two groups : the laparoscopic gastrectomy / robotic gastrectomy (n = 11) and open gastrectomy (n = 39) groups. The short-term outcomes of these procedures were subsequently examined. Results : The laparoscopic gastrectomy / robotic gastrectomy group had significantly shorter hospital stays and lower intraoperative blood loss than the open gastrectomy group. The overall complication rates were 12.8% (5 of 39 patients) and 0% (0 of 11 patients) in the open gastrectomy and laparoscopic gastrectomy / robotic gastrectomy groups, respectively (P = 0.1). Conclusions : Laparoscopic gastrectomy / robotic gastrectomy may be a surgical option after chemotherapy for patients with advanced gastric cancer. J. Med. Invest. 69 : 261-265, August, 2022.

The Journal of Medical Investigation : JMI


High Ligation of the Inferior Mesenteric Artery Induces Hypoperfusion of the Sigmoid Colon Stump During Anterior Resection.

Anastomotic leakage (AL) after colorectal surgery is associated with insufficient vascular perfusion of the anastomotic ends. This study aimed to evaluate the effect of high vs. low ligation of the ileocolic artery and inferior mesenteric artery, respectively, on the vascular perfusion of the bowel stumps during ileocecal resection (ICR) and anterior rectal resection (AR). We retrospectively evaluated patients who underwent ICR or AR between 2016 and 2020. Real-time indocyanine green fluorescence angiography was performed to measure the fluorescence time (FT) as a marker of the blood flow in the proximal and distal stumps before anastomosis. Thirty-four patients with lower right-sided colon cancer underwent laparoscopic ICR. Forty-one patients with rectosigmoid colon or rectal cancer underwent robotic high AR (HAR) ( = 8), robotic low AR (LAR) ( = 6), laparoscopic HAR ( = 8), or laparoscopic LAR ( = 19). The FT was similar in the ileal and ascending colon stumps ( = 1.000) and did not differ significantly between high vs. low ligation of the ileocolic artery ( = 0.934). The FT was similar in the sigmoid colon and rectal stumps ( = 0.642), but high inferior mesenteric artery ligation significantly prolonged FT in the sigmoid colon during AR compared with low ligation ( = 0.004), indicating that the high ligation approach caused significant hypoperfusion compared with low ligation. The AL rate was similar after low vs. high ligation. Low vascular perfusion of the bowel stumps may not be an absolute risk factor for AL. High inferior mesenteric artery ligation could induce sigmoid colon stump hypoperfusion during anterior rectal resection.


The role of the immunoescape in colorectal cancer liver metastasis.

The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.


Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.

As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line. A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again. Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced. Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.


The BAFF/NF B axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.

The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7 ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7 -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NF B-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7 cells, the previously increased malignancy and BAFF/NF B axis in Huh7 -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NF B pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NF B axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.


A Transabdominal Robotic Purse-String Suture Technique for Transanal Total Mesorectal Excision.

Transanal total mesorectal excision (TaTME) is a novel technique that overcomes the problem of access to the deep pelvis during radical surgery for mid-rectal and lower rectal cancer. Although TaTME has several important steps, the creation of the distal purse-string suture following TaTME plays an important role in ensuring the integrity of the colorectal anastomosis. However, this procedure represents a major technical challenge for the surgeon. Robot-assisted surgery may make this suturing procedure easier than laparoscopic surgery because it permits intuitive wrist movements and a three-dimensional view. The aim of the present study was to investigate the usefulness of transabdominal robotic purse-string suture during anastomosis in TaTME. Twenty-seven patients, who underwent anastomosis using a single stapling technique (SST) during the TaTME of mid-rectal or lower rectal cancer, were enrolled in the study. The patients were allocated to two groups: 11 patients underwent transabdominal robotic purse-string suturing (the Robot group) and 16 patients underwent transanal purse-string suturing (the Transanal group). The characteristics and short-term surgical outcomes of the participants were compared between the two groups. The Robot group tended to have a shorter purse-string suturing time (541 206 seconds versus 729 310 seconds; = .07). Regarding the shape of the "donut" after SST anastomosis, in the Transanal group, 5 of the 16 participants had incomplete donuts with muscular defects and required additional suturing, whereas in the Robot group, all the participants had complete donuts ( = .04). Transabdominal robotic purse-string suturing may facilitate the suturing procedure and contribute to reliable anastomosis.

Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A


Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer.

The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host-tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer.


Intestinal hypoperfusion in patients with Crohn's disease revealed by intraoperative indocyanine green fluorescence imaging.

Anastomotic leakage has been reported as an independent risk factor for surgical recurrence at the anastomotic site in patients with Crohn's disease. An inadequate blood supply may contribute to this leakage. Real-time indocyanine green angiography has been useful for confirming vascular perfusion of the intestines. The aim of this study was to evaluate the use of intraoperative indocyanine green angiography to detect vascular perfusion of the intestines during ileocaecal resection in patients with Crohn's disease and colon cancer. We retrospectively evaluated the medical records of 26 consecutive patients with colon cancer arising in the caecum or ascending colon and 3 consecutive patients with Crohn's disease without a history of disease-related surgery. The patients in the 2 cohorts had undergone ileocaecal resection at Tokushima University Hospital between January 2018 and January 2021. After ileocaecal resection, blood flow was evaluated in ileal (oral) and colon (anal) stapled stumps by indocyanine green fluorescence angiography. The fluorescence time was defined as the time from indocyanine green injection and flush of the injection route to the point when the stump showed the strongest fluorescent signal in the monitor. The fluorescence time for the ileal and colon stumps in patients with Crohn's disease was 43.3 8.8 s each and was significantly longer than the fluorescence time in the patients with colon cancer (29.4 6.5 s and 29.6 6.8 s, respectively) (P < 0.05). Intraoperative indocyanine green fluorescence imaging is safe and reproducible for assessing intestinal perfusion prior to anastomosis in patients with colon cancer and Crohn's disease.


The influence and countermeasure of obesity in laparoscopic colorectal resection.

The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ·25 kg/m (n = 113) and those with a BMI <25 kg/m (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ·28 kg/m who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m) undertook a PWLP including caloric restriction and exercise for 29.6 (15-70) days. The effects of this program were evaluated. Study 1: The BMI ·25 kg/m group had a prolongation of operation time and hospital stay than the BMI <25 kg/m group. Study 2: The patients achieved a mean weight loss of 6.9% (-6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ·25 kg/m group. Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR.


Effect of TU-100 on Peyer's patches in a bacterial translocation rat model.

Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 104 m vs 29.4 104 m, < .05), but improved in the TU-100 group (15.4 104 m, < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 4.9 vs 5.1 10.3 vs 17.9 17.8). The CD4 cells were increased in the BT group ( < .05) compared to the control group but decreased in the TU-100 group. The Foxp3 cells were increased in the BT group compared to the control group ( < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF- , TNF- mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch.


Robotic-assisted total gastrectomy in a patient with gastric cancer associated with situs inversus totalis: With video.

Situs inversus totalis (SIT) refers to an inverted position of the major visceral organ as a "mirror image" of the regular location. We present a video of a robotic-assisted total gastrectomy in a 84-year-old man with SIT. The patient was diagnosed with advanced gastric cancer in the U region. The port placement was done as mirror images of our usual settings. Lymph node dissection was performed with a completely reverse approach to the usual procedure. After total gastrectomy, an intracorporal esophagojejunostomy was performed by circular method. All procedures were performed safely with no intraoperative complications and the patient was discharged uneventfully. Pathological diagnosis confirmed moderately differentiated adenocarcinoma and the depth of invasion was to the subserosa; there were five metastatic lymph nodes. In patients who have gastric cancer with SIT, a robotic-assisted total gastrectomy can be performed safely without surgical complication. Robots are useful for performing a total gastrectomy in SIT.


Pre-operative Weight Loss Program for Obese Patients Undergoing Laparoscopic Gastrectomy.

Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) 28 and BMI < 28kg /2. The influence of BMI in LG surgery was investigated. Study2 : The BMI 28 kg /2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI 28kg /2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg /2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI 28kg /2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG. J. Med. Invest. 68 : 165-169, February, 2021.

The Journal of Medical Investigation : JMI


A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.

We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 +xaliplatin +evacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 +xaliplatin +evacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

International Journal of Clinical Oncology


Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.

Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 g/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.


SDF-1 expression after preoperative chemoradiotherapy is associated with prognosis in patients with advanced lower rectal cancer.

Stromal cell-derived factor-1 (SDF-1) expression is associated with cancer progression, as a biomarker of prognosis. We clarified the significance of SDF-1 expression on chemoradiotherapy (CRT) resistance and prognosis in advanced lower rectal cancer patients. We evaluated 98 patients with advanced lower rectal cancer who underwent preoperative CRT. All patients received 40 Gy of radiation therapy, with concurrent chemotherapy containing fluorinated pyrimidines, followed by surgical resection. SDF-1 expression in surgical specimens was examined by immunohistochemistry. We divided the patients into SDF-1-positive- (n = 52) and SDF-1-negative groups (n = 46) and compared the clinicopathological factors and survival rates. The SDF-1-positive group was more resistant to CRT than the SDF-1-negative group (non-responder rate, 63.5% vs. 47.8%, respectively ; p = 0.12). Overall survival (OS) in the SDF-1 positive group was significantly poorer vs. the SDF-1-negative group (5-year OS, 73.4% vs. 88.0%, respectively ; p = 0.02), and disease-free survival (DFS) was worse (5-year DFS, 61.0% vs. 74.1%, respectively ; p = 0.07). Multivariate analysis confirmed that SDF-1 expression was a significant independent prognostic predictor of OS (p = 0.04). SDF-1 expression after preoperative CRT is significantly associated with a poor prognosis in advanced lower rectal cancer patients and is a promising biomarker. J. Med. Invest. 68 : 309-314, August, 2021.


Usefulness of a multidisciplinary surgical site infection team in colorectal surgery.

Background : Surgical site infection (SSI) is an adverse event that places a major burden on patients and staff. In this study, we examined the occurrence of SSI and the characteristics of patients referred to the SSI team after colorectal surgery. Methods : In total, 955 patients underwent colorectal surgery at our hospital from 2014 to 2019. Of these 955 patients, 516 received therapeutic support by the SSI team from 2017 to 2019. All patients were evaluated using an SSI surveillance sheet, and we checked for reports of SSI once a month. Each attending physician performed SSI prophylaxis (use of new instruments before wound irrigation and closure). Results : SSI occurred in 80 (8.4%) patients. The incidence of SSI and the incidence of surface SSI were higher in the patients who did not receive intervention by the SSI team than in the patients who did. Organ /pace SSI occurred in 18 patients. Among patients with surface SSI, Enterococcus was the most commonly detected bacteria. Among the 18 patients with organ /pace SSI, 5 developed anastomotic leakage and 4 developed intra-abdominal abscesses. Conclusions : An SSI team for prevention and treatment of infection may contribute to reduction of SSI. J. Med. Invest. 68 : 256-259, August, 2021.


Impact of CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) expression in gastric cancer.

Background : CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1 (PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods : A total of 105 patients who had undergone curative surgical resection for stage II /II GC at Tokushima University Hospital were included in this study. The expression of CMTM6 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results : CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS : 57.2% vs. 79.2%, respectively ; p < 0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS : 52.8% vs. 72.4%, respectively ; p < 0.05). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p < 0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p = 0.07). Conclusions : CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC. J. Med. Invest. 68 : 362-367, August, 2021.


夢を実現し，輝く女性外科医たち-求められるサポート体制と働き方改革- 地方外科から発信するダイバーシティ・インクルージョンを目指した取り組み


Impact of sidedness of colorectal cancer on tumor immunity.

Clinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity. A total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined. Clinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS. The prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.


HIF-1 expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis.

The role of hypoxia-inducible factor-1 (HIF-1 ) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1 expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1 expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1 expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. Activated HSCs induced HIF-1 mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1 expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1 expression in primary CRC. However, HIF-1 expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1 positive expression in liver metastasis had poor prognosis. HIF-1 expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.


Usefulness of an ICG fluorescence catheter system in TaTME for avoiding intraoperative urethral injury.

Sometimes intraoperative urethral injury occurs in Transanal total mesorectal excision (TaTME). The aim of this study is to investigate the usefulness of indocyanine green (ICG) fluorescent catheter system for avoiding intraoperative urethral injury in TaTME in experimental model. A urethral catheter was filled with the mixture of albumin and ICG and raw hams were applied in layers as the surrogate model of rectourethral muscle. The detectability of ICG fluorescence in this catheter was investigated by using laparoscope-type fluorescence camera system. Fluorescence was detected when ICG was mixed with albumin or peripheral blood. ICG fluorescence could be detected within 4 mm depth of layered raw hams as the surrogate model. Quantitative analysis of the picture detected that ICG fluorescence plateaued in lower concentration than that of serum. ICG fluorescent catheter system may be useful for avoiding intraoperative urethral injury in TaTME. J. Med. Invest. 67 : 285-288, August, 2020.

The Journal of Medical Investigation : JMI


Trans-abdominal Pre-peritoneal (TAPP) Inguinal Hernia Repair with Liquid-injection and Gauze Dissection.

Purpose : This report describes a novel technique for trans-abdominal pre-peritoneal (TAPP) inguinal hernia repair using liquid injection and gauze dissection. Methods : Twenty-five cases underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection. Before the initial peritoneal incision, liquid injection was performed percutaneously into the pre-peritoneal space at the outside of the internal inguinal ring and the inside of the seminal duct. Especially, at the inside of the seminal duct, the liquid was injected into the space between the superficial and deep lobe of pre-peritoneal fascia. Gauze was effectively used to dissect this liquid-injected space. Results : In comparison with the cases of inguinal hernia repair without liquid-injection and gauze dissection, the cases who underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection experienced shorter operation times and no complications or recurrence. Conclusions : TAPP inguinal hernia repair with liquid-injection and gauze dissection appears to be a safe and feasible procedure. J. Med. Invest. 67 : 271-273, August, 2020.


Desmoid-type fibromatosis difficult to distinguish from GIST : A case report.

Background : Desmoid-type fibromatosis is a very rare disease that has no characteristic image findings, so it is often difficult to differentiate from gastrointestinal stromal tumor (GIST). A case of desmoid-type fibromatosis that was difficult to differentiate from GIST is reported. The decisive factor in the diagnosis was positive nuclear immunostaining for β-catenin nucleus. Case presentation : A man is his 30s had no significant past medical history, including no abdominal surgery. A medical check-up found a large tumor in the right lateral abdomen. After some examinations, a preoperative diagnosis of GIST was made, and open ileocecal resection was performed. However, the final diagnosis based on the pathological findings was desmoid-type fibromatosis. Conclusions : We should consider desmoid-type fibromatosis when we find a large abdominal mass, but it may be difficult to diagnose based only on imaging findings. Immunohistochemical examination of the specimen may make the diagnosis. J. Med. Invest. 67 : 375-377, August, 2020.


Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma.

The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC. Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40 s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated. The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim +ypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim +ypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim +ypo group: 72%). Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.


Usefulness of virtual three-dimensional image analysis in inguinal hernia as an educational tool.

The pre-operative three-dimensional (3D) imaging technique has resulted in a better surgical outcome for patients and has been used as an education and diagnostic tool. However, there are no reports concerning the usefulness of the 3D imaging technique in laparoscopic transabdominal pre-peritoneal repair (TAPP) so the aim of this study was to investigate the usefulness of the 3D imaging technique in laparoscopic TAPP as an educational tool for medical students. Six (6) patients who underwent laparoscopic TAPP for inguinal hernia were enrolled in this study. 3D reconstruction was performed from pre-operative computed tomography (CT) and the usefulness of pre-operative 3D simulation compared with intra-operative laparoscopic imaging was validated. Moreover, thirty (30) medical students at the university completed a multiple-choice questionnaire (MCQ) to determine the level of their satisfaction and understanding of anatomy resulting from the study. The local anatomy of the patients was identified as the same during the operation as the pre-operative 3D simulation. The results of the MCQ showed that most of the medical students were extremely (23%) or very (67%) satisfied with the effect of pre-operative 3D simulation on the quality of the surgery. Moreover, most students could understand the surgery anatomy by the 3D simulation extremely well (40%) or very well (47%) and agreed on the usefulness of this procedure for learning anatomy. Pre-operative 3D simulation increases the understanding of detailed anatomy and virtual three-dimensional image analysis in laparoscopic TAPP is useful as an educational tool for medical students.


【最先端医療を支える病理学】消化管最新外科手術における病理の役割

【最先端医療を支える病理学】消化管最新外科手術における病理の役割

Recently, the surgical procedure of gastrointestinal tract has been developing. Compared with open surgery, laparoscopic surgery showed less invasiveness, intraoperative blood loss, postoperative pain and hospital stay. Since2018, robotic surgery in gastric and rectal cancer could be covered by insurance. Robotic surgery enables to perform minimally invasive surgery with an advanced set of instruments and a 3D high-definition view of the surgical area. So, robotic surgery enables to perform more accurate and less invasive surgery. In order to secure the curability and provide less invasive surgery, the role of pathology is very important. The aim of this study is to introduce a new surgical procedure and the role of pathology in gastrointestinal tract cancer.


The usefulness of intraoperative X-ray fluoroscopy in avoiding urethral injury during transanal total mesorectal excision.

Urethral injury is one of the most important complications that can occur during transanal total mesorectal excision in male patients with rectal cancer. This report shows the usefulness of intraoperative X-ray fluoroscopy to avoid urethral injury associated with transanal total mesorectal excision. Real-time navigation using fluoroscopy was performed to check the distance between the urethra and the dissection line at the level of the exposed rectourethral muscle, the middle level of the divided rectourethral muscle, and the level at which the prostate was identified. The dissection was completed transanally up to the level of peritoneal reflection on the anterior side without urethral injury. Pathological examination confirmed that the circumferential resection margin was tumor free. This novel technique using intraoperative X-ray fluoroscopy is an easy-to-use approach that helps prevent urethral injury in male patient who undergo transanal total mesorectal excision for rectal cancer.


The Role of Neutrophil-to-lymphocyte Ratio on the Effect of CRT for Patients With Rectal Cancer.

Neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation and could be a predictive factor in malignant tumors. The aim of this study was to investigate the impact of NLR in patients with lower rectal cancer who received preoperative chemo-radiotherapy (CRT). Forty-eight patients with lower rectal cancer who underwent preoperative CRT and curative resection were enrolled. Blood samples were obtained before and after CRT. The relationship of NLR with clinical outcome was investigated. Post-CRT NLR was higher compared to pre-CRT NLR. The patients with higher post-CRT NLR tended to have worse pathological response to CRT compared to those with low post-CRT NLR. The patients with high post-CRT NLR showed poorer 5-year overall survival and 3-year disease free survival while there was no correlation according to pre-CRT NLR. The univariate analysis showed that post-CRT stage and post-CRT NLR were associated with a poorer 5-year overall survival. NLR after preoperative CRT could be a potential prognostic indicator for patients with lower rectal cancer.


Clinical Impact of FOLFOXIRI Aiming for Conversion Surgery in Unresectable Multiple Colorectal Liver Metastasis.

We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.


Duodenal-Jejunal Bypass Maintains Gut Permeability by Suppressing Gut Inflammation.

The aim of this study was to investigate gut inflammation and permeability in rats after duodenal-jejunal bypass (DJB) and in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Twelve male 16-week-old obese diabetic rats were divided into three groups: the DJB group, the sham group, and the group injected daily with a GLP-1 receptor agonist (liraglutide). Gut inflammation and the expression of tight junction protein (claudin-1) were analyzed in the three groups at 8 weeks after surgery. The DJB group showed significantly lower levels of gut inflammatory cytokines than the liraglutide group. Claudin-1 showed stronger intensity on immunofluorescent staining in the DJB group than that in the liraglutide group. In summary, DJB surgery might maintain gut permeability via suppression of gut inflammation.


骨髄異形成症候群・発作性夜間血色素尿症合併胃癌に対する腹腔鏡手術の1例

骨髄異形成症候群・発作性夜間血色素尿症合併胃癌に対する腹腔鏡手術の1例


A case of gastric heterotopic pancreas with gastroduodenal invagination.

Heterotopic pancreas (HP) is a rare disease commonly found incidentally on imaging studies, at endoscopy or at autopsy and can be associated with abdominal pain, vomiting, heart burn, gastric outlet obstruction, and even dysphagia in very rare cases. Heinrich's classified HP into three groups, types1-3, with Heinrich's type 3 HP the rarest and difficult to diagnose properly because it has only pancreatic ducts but has no islet and acini. The aim of this study is to report a case of gastric outlet obstruction caused by type 3 HP with gastroduodenal invagination with reference to the literature and diagnosed finally by immuno-histochemical analysis. The case presented is a 40-year-old male presenting with vomiting and abdominal pain. Computed tomography (CT) revealed a cystic mass in the upper abdomen and he was referred to the Tokushima University. Gastric fiber showed that the pedunculated mass originated from the stomach. An open distal gastrectomy was performed. Pathologically, there was small glands proliferation in the sub-mucosal (SM) layer which was membrane and cytoplasm (MUC)1 positive and muscle proliferation. This finding revealed the tumor as HP. Postoperative course was uneventful and the patient was discharged 12 days after surgery. The patient has remained well 12 months after surgery. HP should be considered in the differential diagnosis of SM tumors with gastroduodenal invagination even if this is a rare symptom.


免疫チェックポイント時代における漢方とがん免疫

免疫チェックポイント時代における漢方とがん免疫


A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging.

Dynamic magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) can be used not only to detect liver tumors but also to estimate liver function. The aim of this study was to establish a new EOB-MRI-based formula to determine the resection limit in patients undergoing hepatectomy. Twenty-eight patients with a normal liver (NL group) and five with an unresectable cirrhotic liver (UL group) who underwent EOB-MRI were included. Standardized liver function (SLF) was calculated based on the signal intensity (SI), the volume of each subsegment (S1-S8), and body surface area. A formula defining the resection limit was devised based on the difference in the SLF values of patients in the NL and UL groups. The formula was validated in 50 patients who underwent EOB-MRI and hepatectomy. The average SLF value in the NL and UL groups was 2038 and 962 FV/m2, respectively. The difference (1076 FV/m2) was consistent with a 70% in resection volume. Thus, the resection limit for hepatectomy was calculated as a proportion of 70%: 70 (SLF-962)/1076 (%). The one patient who underwent hepatectomy over the resection limit died due to liver failure. In other 49 patients, in whom the resection volume was less than the resection limit, procedures were safely performed. Our formula for resection limit based on EOB-MRI can improve the safety of hepatectomy.


Usefulness of blood flow evaluation by indocyanine green fluorescence system in laparoscopic anterior resection.

One of the major cause of anastomotic leakage (AL) in anterior resection of the rectum is insufficient blood flow of the remnant colon. The indocyanine green fluorescence system (ICG-FS) can visualize the blood flow of organs intra-operatively. The aim of this study is to investigate the usefulness of ICG-FS for evaluating the blood flow of the remnant colon in laparoscopic anterior resection. Rectal cancer patients (n=24) who underwent laparoscopic anterior resection were included in this study. After resection of the rectum, 7.5mg of ICG was administered intravenously, and the blood flow of the oral stump was evaluated by the ICG-FS. The relationship between the fluorescence time (FT) of the oral stump and AL was investigated retrospectively. Two of twenty-four patients (8.3%) suffered AL. The FT of these two cases were over 60 seconds. In the case with the FT was over 80 seconds, we performed additional resection of the late fluorescence portion of the remnant colon and could avoid AL. In patients whose FT was under 60 seconds, no patients suffered AL. ICG-FS may be useful for evaluating the blood flow of the remnant colon to avoid AL in laparoscopic anterior resection. J. Med. Invest. 66 : 65-69, February, 2019.

The Journal of Medical Investigation : JMI


Utility of virtual three-dimensional image analysis for laparoscopic gastrectomy conducted by trainee surgeons.

Purpose The aim of this study was to investigate the utility the three-dimensional (3D) imaging for laparoscopic gastrectomy performed by trainee surgeons. Methods 3D-reconstruction was performed using multi-detector computed tomography (MDCT) and SYNAPSE VINCENT software. Trainee surgeons made 3D-imaging and checked the anatomical structure. Thirty-three patients who underwent laparoscopic gastrectomy (LG) for gastric cancer were examined. Trainees performed 19 LG, while specialists performed 14 LG. The vascular pattern and the surgical outcomes were evaluated. Result 3D imaging depicted the correct positional relationship between the gastric vasculatures and the organs. Regarding vascular pattern detected by 3D imaging, the origins of the infrapyloric artery were the right gastroepiploic artery in 12 cases (36%), the gastroduodenal artery in eight cases (24%), the bifurcation of the right gastroepiploic artery and gastroduodenal artery in seven cases (21%), and not detected in one case (3%). The types of confluence of the infrapyloric vein were the right gastroepiploic vein in 16 cases (48%), the anterior superior pancreatoduodenal vein in 10 cases (30%), and not detected in seven cases (21%). Surgical outcomes were not different between trainee group using intraoperative 3D image with the specialist in instruction group without the intraoperative 3D image. Conclusions Preoperative 3D imaging might contribute to successful and safe LG by trainee surgeons. J. Med. Invest. 66 : 280-284, August, 2019.


The Effect of Laparoscopic Sleeve Gastrectomy on Obesity and Obesity-related Disease : the Results of 10 Initial Cases.

Introduction : The number of patients who undergo laparoscopic sleeve gastrectomy (LSG) has been increasing. Department of Surgery, Tokushima University performed the first LSG in 2013. The aim of this study was to report the results of the initial ten cases who underwent a LSG. Patients and methods : Ten obese patients : five males and five females ; age range from thirty-three years to fifty-six years (mean age 42.2 years) ; mean body mass index (BMI) 50.3 ; five with diabetes ; nine with hypertension (HT) ; four with hyperlipidemia (HL) ; eight with sleep apnea syndrome (SAS) who underwent LSG were enrolled in this study. The data was analyzed retrospectively and included short- and long-term outcomes. Results : There were no post-operative complications in this study. The %EWL at three and six months and one year post-operative were 44.2%, 50.2% and 48.6% respectively. In three months post-operative the non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) had improved transaminase (AST/ALT), liver to spleen ratio in plain CT value. Improvements were also evident in the obesity-related diseases : diabetes 80% (4/5) ; HT 67% (6/9) ; HL 75% (3/4) ; and SAS 88% (7/8). Conclusion : LSG is a promising option for the treatment of morbid obesity and obesity-related diseases. J. Med. Invest. 66 : 289-292, August, 2019.


Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin 3.

Light emitting-diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro. Human colon cancer cells (HT-29 or HCT-116) were seeded onto laboratory dishes and irradiated with 465-nm LED at 30 mW/cm for 30 minutes. Cell Counting Kit-8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Autophagy and expression of LC-3 and beclin-1 were also evaluated by autophagy assays, RT-PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the G G-protein inhibitor NF023 in these assays. Viability of HT-29 and HCT-116 cells was lower in 465-nm LED-irradiated cultures than in control cultures. LC-3 and beclin-1 expressions were significantly higher in LED-irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC-3 and beclin-1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment. Blue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.


High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.

The aim of this study was to investigate the significance of signal transducer and activator of transcription 4 (STAT4) expression and the correlation between STAT4 and interferon gamma (IFN- ) in patients with gastric cancer. Sixty-two patients who underwent gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA expression was evaluated by quantitative real-time polymerase chain reaction (PCR). Immunohistochemistry was performed to examine CD8 T-cells, and STAT4 and IFN- expression. STAT4 mRNA expression was significantly correlated with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a significant difference between the groups with high and low STAT4 expression (5-year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis revealed that tumor differentiation and STAT4 expression were significant factors for tumor recurrence. High expression of STAT4 in gastric cancer predicted a better clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after gastrectomy.


Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.

Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ·30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ·30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM.


Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.

Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis. One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry. In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues. Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.


Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)- -catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt- -catenin pathway. Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. SFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to -catenin expression (p = 0.005). Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt- -catenin pathway.

EJSO - European Journal of Surgical Oncology


【100字de看護・説明を深める!きわめる!消化器外科の病棟で行う治療・処置】

【100字de看護・説明を深める!きわめる!消化器外科の病棟で行う治療・処置】


Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.


Limited lymph node dissection in elderly patients with gastric cancer.

The number of elderly patients with gastric cancer is continuing to increase along with the life expectancy of the general population. The purpose of this study was to investigate both the impact of age on postoperative outcome and the effect of limited lymph node dissection for elderly patients. Patients were classified into the following three groups: Group A, ·80 years old (n=44); Group B, 70-80 years old (n=139); Group C, <70 years old (n=219). Postoperative complication and survival rates were compared between the three groups Results: Limited lymph node dissection was performed significantly more frequently in Group A. In terms of surgery-related complications, no significant difference was seen between groups. In terms of general related complications, the complication rate increased with age, from 4% in Group C to 13% in Group B and 14% in Group A (p<0.05 each). Although limited lymph node dissection was frequently performed in Group A, cancer-specific survival showed no significant difference in R0 patients. Limited lymph node dissection for gastric cancer did not affect the cancer-specific survival in elderly patients.

The Journal of Medical Investigation : JMI


Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.

Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.


Effect of light irradiation by light emitting diode on colon cancer cells.

Recent studies have demonstrated the efficacy of irradiation from light emitting diodes (LED) for wound healing, anti-inflammation and anticancer therapies. However, little is known about the effects of visible light in colon cancer cells. The purpose of this study was to evaluate the biological response (including gene expression changes) of human colon cancer cells to different wavelengths of LED irradiation. Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. The cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase-3, capase-8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. LED irradiation at 465 nm inhibited the proliferation of HT29 cells and of HCT116 cells. Notably, LED irradiation at 465 nm promoted apoptosis inHT29 cultures via the extrinsic apoptosis pathway and the MAPK pathway.


Protein kinase Cι is a new prognostic factor in gastric cancer.

Protein kinase Cι (PKCι) is an important oncogenic K-ras effector, and its expression is correlated with tumor angiogenesis. The role of PKCι in gastric cancer remains unclear. The aim of this study was to clarify the role of PKCι in gastric cancer. Twenty-eight patients with gastric cancer who underwent gastrectomy were enrolled in this study. The expression of PKCι mRNA was determined, as were the clinicopathological factors. The patients were divided into PKCι high and low expression groups. The 5-year survival rate, ERK mRNA level and VEGF mRNA level were compared between the two groups. The prognostic factors were investigated by a multivariate analysis. High expression of PKCι was observed to be associated with a lack of differentiation, tumor invasion ≥muscularis propria≤, stage III and IV disease and peritoneal dissemination. The 5-year survival rate in the PKCι high group was lower than that in the PKCι low group. The multivariate analysis revealed that a high expression level of PKCι was an independent prognostic factor. The expression levels of ERK and VEGF in the PKCι high group were higher than those in the PKCι low group. Our results indicate that PKCι is correlated with tumor progression and angiogenesis. PKCι may be a new prognostic factor for gastric cancer.


Expression of Stathmin1 in gastric adenocarcinoma.

Over expression of Stathmin1 (STMN1), activation-induced cytidine deaminase (AID) and protein kinase C iota (PKCi) proteins participate in the regulation of carcinogenesis. In the present study, we investigated the expression of STMN1 in patients with gastric adenocarcinoma and also determined the correlation of STMN1 with AID and PKCi proteins. This study was conducted in the Tokushima University Hospital between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma. Stathmin1, AID and PKCi protein expressions were evaluated by immuno-histochemistry in gastric adenocarcinoma. A strong expression of STMN1 was significantly associated with gender- and poorly differentiated gastric adenocarcinoma (p<0.05). A high mRNA level of STMN1 was found in the tumor tissue of gastric adenocarcinoma compared to non-tumor tissue (p<0.05). In addition, STMN1 expression was significantly correlated with AID and PKCi protein expressions in gastric adenocarcinoma (p<0.05). High mRNA level of the Stathmin1 gene was significantly expressed in gastric tumor tissue than non-tumor and strong expression of STMN1 protein is correlated with poorly-differentiated gastric adenocarcinoma.


Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair.

Incisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied. Monofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed. Hybrid techniques already combine mini-laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice.


Role of CD151 expression in gallbladder carcinoma.

CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. CD151 is involved in several pathologic activities associated with tumor progression, including metastasis and angiogenesis. The aim of this study was to clarify the clinical use of CD151 expression in gallbladder cancer (GBC). Forty-five patients with GBC who had undergone operative treatment were enrolled in this study. Expressions of CD151 in the resected GBC specimens were evaluated with anti-CD151 antibody. The patients were divided into positive and negative groups according to CD151 expression: CD151-positive group (n = 26) and CD151-negative group (n = 19). Clinicopathologic factors, including Ki-67 and matrix metallopeptidase 9, also were compared between the two groups. CD151-positive expression was 58% and correlated with poorer prognosis; 5-year survival of CD151-positive and CD151-negative groups was 29% and 78%, respectively (P = .006). CD151 expression also correlated with lymphatic invasion and curability. Multivariate analysis revealed that CD151-positive expression was an independent prognostic factor (hazard ratio 2.97, P = .02). In addition, CD151 expression correlated with matrix metallopeptidase 9 expression (P < .05) but not with Ki67 expression. Those findings suggested that CD151-positive expression might be a potential prognostic indicator and one of the target molecules for the regulation of tumor metastasis for patients with GBC.


Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids.

The aim of this study is to investigate the mechanisms of improvement in insulin resistance after duodenal-jejunal bypass (DIB), especially regarding the correlation between bile acids and glucagon-like peptide-1 (GLP-1). SD rats were divided into two groups: DIB or Sham group. Blood glucose, insulin, GLP-1, bile acids, and the number of L cells in the small intestine were investigated three weeks after the operations. Next, to assess the effect of the bile acids on GLP-1 secretion in ileum, bile diversion model (=inhibition of rapid bile exposure to the ileum; BD group) were performed and postoperative glycemic parameters were measured. DJB improved insulin resistance and increased GLP-1 compared with sham. Higher bile acids in DJB were found than that in sham. The number of L cells in the common limb of DJB was increased compared with that in the distal segment of sham. In BD group, insulin resistance had not improved. GLP-1, bile acids, and the number of L cells revealed no significant changes compared with sham. DJB has a potential to improve insulin resistance, which may be related to enhanced GLP-1 secretion through the increase of bile acids in the common limb of the small intestine.


Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.

Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.


The role of activation-induced cytidine deaminase expression in gastric adenocarcinoma.

Gastric adenocarcinoma is one of the most common malignant tumors and the leading cause of malignancy-related death worldwide. Studies have reported overexpression of activation-induced cytidine deaminase (AID) and protein kinase c iota (PKCi) proteins showing involvement in the regulation of carcinogenesis. In the present study, we investigated the expression of AID and PKCi in patients with gastric adenocarcinoma and determined the correlation between these proteins. This study was conducted between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma at the Tokushima University Hospital. AID, PKCi and mutated p53 protein expressions were evaluated by immunohistochemistry in gastric adenocarcinoma. High AID and PKCi expression was significantly (p<0.05) associated with poorly-differentiated gastric adenocarcinoma. In addition, PKCi expression was significantly correlated with clinicopathological findings such as a lymph node metastasis, and venous and lymphatic invasion (p<0.05). Furthermore, AID expression was significantly correlated with PKCi and mutated p53 protein expression in gastric adenocarcinoma (p<0.05). High AID and PKCi expressions were significantly correlated with poorly-differentiated gastric adenocarcinoma.


Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.

Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects.


Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases.

Recently, consensus on the optimal strategy for resectable synchronous colorectal liver metastases (LM) seems to have shifted toward simultaneous resection. However, there are still relatively few reports about simultaneous laparoscopic resection. The aim of this study is to evaluate the outcomes of patients who underwent simultaneous laparoscopic resection. We evaluated 14 patients who underwent simultaneous resection of primary colorectal cancer and LM in our hospital from 2004 to 2012. Patients were selected by matched pair analysis based on the number of LM (≤4) and tumor size (≤5 cm). We divided them into two groups: the simultaneous laparoscopic resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n = 7). Clinical and oncologic outcomes were compared between the groups. The Lap-S patients were significantly older than the Open-S patients. The mean operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the Open-S group (496 mL). There was no surgical mortality in either group. The incidence of postoperative complications in the Lap-S and Open-S groups was 12.3% and 33.0%, respectively. The mean postoperative hospital stay was significantly shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There was no significant difference in long-term survival between the two groups. Lap-S patients had equivalent long-term outcomes to Open-S patients. Therefore, given its technical feasibility and safety, Lap-S may be one of the most promising options in selected patients.