The interaction between cancer associated fibroblasts and tumor associated macrophages via the osteopontin pathway in the tumor microenvironment of hepatocellular carcinoma.

Cancer-tumor associated macrophage (TAM)-cancer associated fibroblast (CAF) interactions are an important factor in the tumor microenvironment of hepatocellular carcinoma. Hepatic stellate cells (HSCs) were cultured with cancer cell-conditioned medium (Ca.-CM), TAM-CM and CAF-CM, and the expression of CAF markers were evaluated by RT-PCR. Whether HSCs cultured with Ca.-CM, TAM-CM and CAF-CM contributed to the enhanced malignancy of cancer cells was examined using proliferation, invasion and migration assays. Furthermore, the differences between these three types of CM were evaluated using cytokine arrays. HSCs cultured with Ca.-CM, TAM-CM and CAF-CM showed significantly increased mRNA expression of SMA, FAP and IL-6. All HSCs cultured with each CM exhibited significantly increased proliferation, invasion and migration of cancer cells. The osteopontin concentration was significantly higher in HSCs cultured with TAM-CM than the other CAF-CMs. Osteopontin inhibition significantly reduced osteopontin secretion from HSCs cultured with TAM-CM and suppressed the proliferation and invasion of cancer cells enhanced by HSCs cultured with TAM-CM. We observed enhanced osteopontin secretion from TAMs, and this increased osteopontin further promoted osteopontin secretion from HSCs cultured with TAM-CM, leading to increased malignancy. For the first time, we demonstrated the importance of cancer-TAM-CAF interactions via osteopontin in hepatocellular carcinoma.


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.


Transoral Anvil Delivery System With Tension-Free Method for Esophagojejunostomy After Laparoscopic Total Gastrectomy Prevents The Postoperative Stenosis.


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.


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.


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


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.


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.


Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.

Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. UMIN000026292.


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.


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.


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.


CD133 expression is correlated with poor prognosis in colorectal cancer.

Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear. Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis. In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor. CD133 expression is correlated with poor prognosis in CRC.


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.


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.


P1胃癌に対しS-1+PTXi.p.を行い5年生存が得られた1例

P1胃癌に対しS-1+PTXi.p.を行い5年生存が得られた1例


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.