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In colorectal cancer (CRC), the indication for immune checkpoint inhibitors is determined by the microsatellite instability status of the tumors. However, an optimal biomarker for their indication has not been fully identified to date. This study aimed to establish the clinicopathologic importance of the Immunoscore (IS) in CRC and to clarify the relationships between the IS, programmed death-ligand 1 (PD-L1) expression, and tumor-associated macrophages. In 132 cases, CRC was diagnosed and surgically treated in our department from 2009 to 2010. Immunohistochemical staining using primary antibodies PD-L1, CD3, CD8, CD68, and CD163 was performed. The IS was determined according to the proposal of an international task force. Statistical analyses were performed to investigate the correlation between the IS, clinicopathologic variables, and expression of immune checkpoint molecules. The overall survival (OS) and relapse-free survival (RFS) in the high-IS group (I3–4) were significantly better than in the low-IS group (I0–2) (OS: P = 0.0420; RFS: P = 0.0226). The positivity rate for PD-L1 on tumor cells (tPD-L1) was only 0.8%, whereas that for PD-L1 on interstitial tumor-infiltrating mononuclear cells (iPD-L1) was 18.2%. The iPD-L1-positive group showed significantly better survival in terms of both OS and RFS than the iPD-L1-negative group (OS: P = 0.0278; RFS: P = 0.0253). The findings showed significant correlation between the IS and iPD-L1 expression (P

Signet ring cell carcinoma (SRCC) is a rare pathological type of colorectal cancer, of which the clinicopathological features and genetic background have not yet been fully investigated. Previous research has focused on the optimization of colorectal cancer treatment utilizing consensus molecular subtyping (CMS). However, it is not known what type of CMS would be designated to SRCC treatment. In the current study, of 1,350 patients diagnosed with colorectal cancer who underwent surgery, 14 were diagnosed with SRCC. The case-control cohort that fit the clinical background of the SRCC case was constructed. Statistical comparison between the SRCC group and the case-control cohort was performed among clinicopathological variables. SRCC and well to moderately adenocarcinoma case mRNA were submitted to microarray analysis and CMS analysis. Compared with the case-control cohort, the SRCC group was located more in the right-sided colon, the lymphatic invasion was more severe and the peritoneal dissemination was more frequent. The cancer-specific survival and the progression-free survival were significantly worse in the SRCC group compared with the case-control cohort. Microarray and CMS analysis identified that one SRCC case was significantly well assigned in the CMS 4 group and the other case was assigned in the CMS 1 group. Gene set analysis revealed the upregulation of EMT related genes and the downregulation of fatty acid, glycolysis, differentiation, MYC, HNF4A, DNA repair genes. In conclusion, the clinical characteristics of SRCC are severe but there is a possibility of the presence of different phenotypes according to CMS analysis.

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p p p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598–2.4586; p p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

We investigated the anti-proliferative effect of quercetin on liver cancer cell lines.Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 μM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin.The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle.Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

Background We investigated the correlation between surgery-related factors and the incidence of leakage after low anterior resection (LAR) for lower rectal cancer. Methods A total of 630 patients underwent colorectal surgery between 2011 and 2014 in our department. Of these, 97 patients (15%) underwent LAR, and are the subjects of this retrospective study. Temporary ileostomy was performed for each patient.Results Anastomotic leakage occurred in 21 patients (21.7%). Univariate analysis showed that operative duration (p=0.0051), transanal hand-sewn anastomosis (p=0.0141), and operation procedure (p=0.0191) were significantly associated with the incidence of leakage. Multivariate analysis showed that underlying disease (p=0.044), transanal hand-sewn anastomosis (p=0.0188), and drain type (p=0.0251) were significantly associated with the incidence of leakage. The propensity score analysis results showed that closed drainage was associated with 6.3 times more postoperative blood loss (mls) in patients experiencing anastomotic leakage compared with open drainage, in the inverse probability of treatment-weighted analysis.Conclusions Our results showed that underlying disease, transanal hand-sewn anastomosis, and the drain type may be risk factors for developing anastomotic leakage after LAR for lower rectal cancer. The notable finding was that the type of drainage was related to the incidence and volume of anastomotic leakage: open drainage was correlated with the incidence of leakage, and closed drainage was correlated with the volume of anastomotic leakage.

Background We investigated the correlations between surgery-related factors and the incidence of anastomotic leakage after low anterior resection (LAR) for lower rectal cancer. Methods A total of 630 patients underwent colorectal surgery between 2011 and 2014 in our department. Of these, 97 patients (15%) underwent LAR and were enrolled in this retrospective study. Temporary ileostomy was performed in each patient. Results Anastomotic leakage occurred in 21 patients (21.7%). Univariate analysis showed a significant association between operative duration (p = 0.005), transanal hand-sewn anastomosis (p = 0.014), and operation procedure (p = 0.019) and the occurrence of leakage. Multivariate regression reanalysis showed that underlying disease (p = 0.044), transanal hand-sewn anastomosis (p = 0.019) and drain type (p = 0.025) were significantly associated with the occurrence of leakage. The propensity-score analysis showed that closed drainage were 6.3 times more likely to have anastomotic leakage than open drainage in relation to the amount of postoperative drainage (ml), according to the inverse probability of treatment-weighted analysis. Conclusions Our results indicate that underlying disease, transanal hand-sewn anastomosis, and closed drain may be a risk and predictive factors for anastomotic leakage after LAR for lower rectal cancer. The notable finding was that closed drainage was related to the occurrence of anastomotic leakage and closed drainage was correlated with less volume of postoperative drain discharge than open drain.

Summary: Background: Groin hernias are frequently seen in clinical practice. The purpose of this study was to determine the rate of patients who might have latent groin hernia. Methods: During laparoscopic abdominal surgery, we observed the area around the groin lesion and attempted to evaluate the degree of recess at myopectineal orifice. The classification defining the recess was as follows: Grade 0: no recess, Grade I: slight recess with a visible bottom, Grade II: deep recess with an invisible bottom, Grade III: other organ invaginated into the recess, and Grade IV: confirmed bulging on the body surface. Results: From 2009 to 2011, 46 patients were enrolled. A recess around myopectineal orifice were detected in 20 patients. The lesions were as follows: 11 on the lateral side of the inferior epigastric artery (IEA), five on the internal side of the IEA, three at both sites and one found at the femoral ring. According to the grade classification of these groin hernias, 26 (57%) were Grade 0, 14 (30%) Grade I, 4 (9%) Grade II, 1 (2%) Grade III, and 1 (2%) Grade IV. Conclusions: This study showed that rate of patients with asymptomatic latent groin hernias is relatively high in Japanese. Keywords: Groin hernia, Latent hernia, Laparoscopic surgery

Aim Cancer‐associated fibroblasts (CAFs) generated by bone marrow‐derived mesenchymal stem cells (BM‐MSCs) play an important role in cancer progression. In this study, we investigated the relationships of BM‐MSCs and CAFs in resected gastric cancers with the clinicopathological factors of patients. Methods We analyzed 120 gastric cancer patients who underwent gastrectomy. Immunostaining was performed with an anti‐CD271 antibody (BM‐MSCs) and anti‐α‐smooth muscle actin (αSMA) antibody (CAFs). Staining intensity was used to divide patients into low and high expression groups. Observation sites in cancer tissues were invasive, central, and whole portions. Results Expression of αSMA was significantly related to depth of tumor invasion (T), lymph node metastasis (N), lymphatic invasion (ly), venous invasion (v), and stage. Expression of CD271 was significantly related to v, stage, stromal volume, and tumor infiltration pattern (INF). Overall survival (OS) of the high expression group was significantly lower than that of the low expression group for both αSMA and CD271. Multivariate analysis showed that N, αSMA (whole), and CD271 (invasive) were independent prognostic factors. Conclusions Cancer‐associated fibroblasts and BM‐MSCs are related to the progression, invasion, and prognosis of gastric cancer and may be therapeutic targets of gastric cancer., We immunohistochemically examined bone marrow‐derived mesenchymal stem cells and cancer‐associated fibroblasts in gastric cancer tissues and obtained results indicating that they were associated with tumor infiltration and stroma, and closely related to prognosis.

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD., Scientific Reports, 11, art. no. 16260; 2021

Objective We analyzed the cases of gastric cancer patients who underwent surgical treatment during the 16 years from 1997 to 2012 at our department to clarify these trends. Methods The subjects were 810 patients who underwent surgery for gastric cancer between 1997 and 2012. We divided the cases into the early-period group (1997–2006) treated before the introduction of laparoscopy, and the late-period group (2007–2012). We compared the clinicopathological factor and survival rates between the early- and late-period groups. Results The average patient age was higher in the late-period group than in the early-period group. Tumor localization showed an increased proportion in the U-region in the late period, and histological type in the late period showed a higher proportion of poorly differentiated cases. The cases receiving adjuvant chemotherapy increased in the late period. The five-year survival rate in the late-period group was shown to be equivalent to that in early-period group. Although the proportion of poorly differentiated cases was increased in late-period group, their survival rate was equivalent, probably because of the use of adjuvant chemotherapy. Conclusions Distinct characteristics were seen over the period of 16 years. It is important to continue the analysis of surgical outcomes to identify trends that need to be addressed.

Key Clinical Message There are very few reports of esophageal carcinoma producing granulocyte colony‐stimulating factor (G‐CSF). G‐CSF‐producing esophageal squamous cell carcinoma is an extremely aggressive carcinoma. Leukocyte counts, neutrophil counts, and serum C‐reactive protein levels may be markers of its progression.

Pharmacologic thromboprophylaxis is recommended for preventing pulmonary embolism according to some abdominal surgery guidelines. However, few reports have so far described pharmacologic thromboprophylaxis after pancreatic surgery. In addition, concern remains regarding postoperative bleeding due to pharmacologic thromboprophylaxis. We investigated the safety and efficacy of enoxaparin, a low-molecular-weight heparin, as postoperative pharmacologic thromboprophylaxis after pancreatic surgery. In this record-based retrospective study, the sample population comprised 151 consecutive patients who underwent pancreatic surgery and received enoxaparin postsurgery at our institute between November 2009 and March 2014. The primary outcome was the incidence of symptomatic pulmonary embolism after surgery, and the secondary outcome was the incidence of bleeding as an adverse effect of enoxaparin injection. No symptomatic pulmonary embolism events occurred during the study. Major and minor bleeding events were experienced in 5 (3.3%) cases each. Four of these major events were caused by the rupture of a pseudoaneurysm with a pancreatic fistula not related to enoxaparin, and all events were treated safely with no mortalities in the study period. We found no factors related to minor bleeding with enoxaparin injection in a statistical comparison. The use of enoxaparin is considered to be safe and effective for pulmonary embolism prophylaxis after pancreatic surgery.

Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program. We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor. The purposes of the DAT program are as follows: To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

Introduction Round ligament varicosities (RLV) are not well-known and they are usually caused by pregnancy. Although the groin swelling of RLV mimics an inguinal hernia, it is difficult to distinguish between them through clinical examination alone, and there have been few published reports on this topic, especially from Asia. Case presentation A 37-year-old Japanese woman complained of left groin swelling for 2 weeks at her 28th week of gestation of her first pregnancy. According to a physical examination, she had a soft, painless swelling in the superficial inguinal ring of the left groin. An inguinal hernia was suspected and she was thus scheduled to undergo herniorrhaphy. However, since she had varicosities in the left labia majora, she first underwent color Doppler ultrasonography and a final diagnosis of round ligament varicosities was this made. Her symptoms resolved after delivery of her baby. Discussion We herein report 10 cases of RLV in pregnant Japanese women who were initially suspected of having an inguinal hernia. All of them were suspected to suffer from inguinal hernias after a clinical examination by their attending gynecologist. All of them were diagnosed using gray scale and color Doppler ultrasonography, treated with conservative management, and the symptoms resolved in all cases after the delivery. Conclusion This is the largest report from Asia regarding RLV. To avoid unnecessary surgery in pregnant women, surgeons must be aware of this entity make an accurate diagnosis based of the findings of Doppler ultrasonography., International Journal of Surgery Case Reports, 36, pp.122-125; 2017

Highlights • An internal hernia after retroperitoneal laparoscopic nephrectomy is rare. • Retroperitoneal approach has the risk of making mesocolic defects directly. • To prevent internal hernia, we should close the mesenteric defects intraoperatively., Introduction Small bowel obstruction (SBO) caused by an internal hernia through a mesocolon after retroperitoneal laparoscopic nephrectomy (RLN) is rare. Presentation of case A 66-year-old man who had undergone RLN with bladder cuff excision for a left renal pelvic cancer. After the surgery, he experienced SBO repeatedly. Contrast-enhanced computed tomography (CT) and gastrografin contract radiography through a long tube showed an internal hernia through the mesocolon to the retroperitoneal space where the resected left kidney had been located. We performed a subsequent surgery for the internal hernia. Postoperative course was uneventful and currently he has no recurrence of herniation 6 months post-operatively. Discussion Mesenteric defects that cause an internal hernia can be created inadvertently during RLN when the colon is mobilized medially, and the kidney is being detached from retroperitoneum. The removal of a kidney leads to a potential retroperitoneal space to which small intestine can migrate. While there is no absolute necessity in mobilizing the colon during the retroperitoneal laparoscopic approach, there is still a risk of making mesocolic defects directly in the retroperitoneal space. Conclusion We need to perform operations with sufficient anatomical knowledge of retroperitoneal fascia and careful surgical techniques. The critical thing to prevent an internal hernia following RLN is to close the mesenteric defects intraoperatively. It is also important to suspect an internal hernia and do proper examinations promptly when patients had the symptoms of SBO after nephrectomy.

Background/aim Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. Materials and methods The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. Results MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. Conclusion MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.

Background/aim Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. Materials and methods Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. Results The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. Conclusion NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.

Mixed carcinoma of the pancreas is defined as the concurrent existence of pancreatic ductal carcinoma, acinar cell carcinoma, and/or islet cell carcinoma within the same neoplasm. We herein report a rare case of mixed ductal-acinar cell carcinoma in a 74-year-old man who was undergoing treatment for hypertension and diabetes at another hospital. After an abrupt worsening of his blood glucose control, the patient was referred to our hospital for further evaluation. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging revealed a tumor with a multilocular cystic lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed obstruction of the main pancreatic duct and dilation of the dorsal pancreatic duct; in addition, adenocarcinoma was detected in the pancreatic juice cytology. Based on the abovementioned findings, the patient was diagnosed with carcinoma of the pancreatic head and underwent subtotal stomach-preserving pancreaticoduodenectomy. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with mixed ductal-acinar cell carcinoma. The patient was prescribed TS-1 as postoperative adjuvant chemotherapy upon discharge. However, treatment was discontinued 2 months later due to marked general malaise, and the patient succumbed to tumor recurrence in the residual pancreas 12 months after the surgery.

Background Heat shock protein 70 (HSP70) confers protection against heat shock, oxidative stress, infection, and inflammation in many cell types. A recent study reported that the induction of HSP70 was associated with morphologic protection against ischemia–reperfusion injury (IRI) in the rat small intestine. This study investigated the dynamics of HSP70 in leukocytes during intestinal IRI in a rat model. Materials and methods Serial blood samples were collected at 60-minute intervals up to 240 min from male Wistar rats (n = 15). The rats were divided into three groups of five each: the control group, the nonlethal IRI group, and the lethal IRI group. Rats belonging to the control group underwent a sham operation, and laparotomy was performed on rats in the lethal and nonlethal IRI groups. The nonlethal group experienced a 30-minute clamping of the superior mesenteric artery, and the lethal group experienced a 75-minute clamping of the superior mesenteric artery. The expression of HSP70 messenger RNA (mRNA) in leukocytes was measured by real-time quantitative polymerase chain reaction. Mixed-effects modeling of repeated measures was used to carry out the statistical analysis. The Bonferroni correction was applied to multiple comparisons. A P value Results The expression of HSP70 mRNA in leukocytes increased 60 min after reperfusion in both IRI groups, and it was 12.8 times higher in the lethal group and 3.6 times higher in the nonlethal group compared with the control group. The expression of mRNA in the lethal group was significantly increased compared with the nonlethal group and the control group at 120 and 180 min after reperfusion. At 120 min after reperfusion, the expression of HSP70 mRNA was 6.1 times higher in the lethal group than in the nonlethal group (P = 0.0075) and 17.7 times higher than in the control group (P = 0.0011). At 180 min after reperfusion, the expression of HSP70 mRNA was 6.8 times higher in the lethal group than in the nonlethal group (P = 0.0007) and 4.3 times higher than in the control group (P = 0.0032). Although the expression of HSP70 mRNA in the nonlethal group was elevated in the early stages of reperfusion, there was no difference between the nonlethal group and the control group (P = 0.0212 at 60 min). Conclusions The expression of HSP70 mRNA in leukocytes may be a clinically useful indicator for evaluating pathologic conditions in intestinal IRI.

Abdominoperineal resection (APR) is commonly performed as radical surgical treatment for low rectal cancer near the anus. To improve the postoperative quality of life (QOL), various sphincter-saving operations have been developed. In particular, intersphincteric resection (ISR) was devised as a new concept of sphincter-saving operation. Current protocols now focus on ISR, which differs from conventional hand-sewn coloanal anastomosis (CAA) after ultimate low anterior resection (LAR). However, the efficacy of ISR remains unclear. In this report, the surgical, oncological, and functional outcomes after ISR are reviewed. This review of the literature was conducted by searching the PubMed online database. Articles focusing on conventional hand-sewn CAA were excluded from this study. The mean mortality rate was

3521 Background: dCRT with 5-FU/MMC is a standard treatment for cStage II/III SCCA. S-1 is an oral fluoropyrimidine and has a greater effect on radiosensitivity. We conducted this trial of dCRT with S-1/MMC to determine the recommended dose (RD) of S-1 in dose-finding (phase I) part and to evaluate the efficacy and safety in confirmatory (phase II) part for cStage II/III SCCA. We reported the RD of S-1 and the 3-year survival at 2019 Gastrointestinal Cancers Symposium. We report the final data after 5-year follow-up. Methods: Eligibility criteria included histologically proven SCCA, cStage II/III (UICC 6th), PS 0-1, and age 20-80 years. dCRT consisted of MMC (10 mg/m2 on days 1, 29) and S-1 (60 mg/m2/d in level 0 and 80 mg/m2/d in level 1 on days 1-14, 29-42) with concurrent radiotherapy of 59.4 Gy/33fr. The dose-finding part adopted the 3+3 cohort design. The primary endpoint of confirmatory part was 3-year event-free survival (EFS). The sample size was 65 in the confirmatory part, with one-sided alpha of 5% and power of 80%, threshold and expected 3-year EFS as 60% and 75%. Key secondary endpoints were overall survival (OS) and progression-free survival (PFS) and colostomy-free survival (CFS), and adverse events. Final analysis was planned after 5-year follow-up for all pts. Results: From Feb/2010 to Mar/2015, 69 pts (3 in level 0 and 66 [7 in phase I and 59 in phase II] in level 1) were enrolled. Pts characteristics for level 1 were as follows: M/F, 12/54; Age, median 64 (range 33-80); cStage II/IIIA/IIIB, 29/9/28. Three in level 1 were ineligible and 63 eligible assigned to level 1 were included in efficacy analysis. In the dose-finding part, RD of S-1 was determined as 80 mg/m2/d. The complete response rate was 81% (95% CI, 69.1-90.0%) on central review. With a median follow-up of 5.4 years, 3- and 5-year EFS was 65.0% (90% CI 54.1-73.9%) and 63.4% (95% CI 50.2-73.9%). 5-year OS, PFS, and CFS were 84.1% (95% CI 72.5-91.1%), 84.1% (95% CI 72.4-91.1%), and 73.0% (95% CI 60.2-82.3%), respectively. In a univariable analysis, male sex (p = 0.045) prognosticated for poor OS and cT3 or T4 (p = 0.001), male sex (p = 0.019) and, PS 1 (p = 0.048) prognosticated for poor CFS. Nine (14.3%) of 63 pts at a dose level 1 developed recurrence or disease progression. Locoregional recurrence only and distant metastasis were observed in 1 pts (1.6%) and 8 pts (12.7%) respectively. Among all treated 65 pts, only 5 pts (7.7%) showed grade 3 late toxicities including jejunum obstruction, jejunum ulcer, proctitis, lower gastrointestinal hemorrhage, anal pain, radiation dermatitis, and ureteral stenosis. No Grade 4 or 5 late toxicities were observed. Conclusions: dCRT with S-1/MMC showed acceptable toxicities and favorable 5-year survival and could be a possible treatment option for pts with locally advanced SCCA. Clinical trial information: jRCTs031180002.

Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., “focused cancer immunotherapy”) based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n=28), colon (n=20), bladder (n=20), renal cell (n=15) and malignant lymphoma (n=9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter-alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients. This article is protected by copyright. All rights reserved.

Anastomotic leakage is a major postoperative complication. While cell sheet technology has been gaining popularity in the clinical field, the utility of cell sheets for containing contaminated enteral perforation remains unclear. We established a new gastric perforation rat model and evaluated the efficacy of the myoblast cell sheet to prevent leakage. To establish a suitable rat model, perforations of various sizes were made in the stomach. We then pasted the sheet onto the perforated stomach in our new model. After the operation, the rats were sacrificed and analyzed macroscopically and histologically. Serum levels of C-related protein and hyaluronic acid in the peritoneal cavity washing lavage were also evaluated. An incision 5 mm in length was found to be the most suitable for evaluation of the cell sheet performance. In the rats where the cell sheet had been pasted onto the perforation site, we noted less adhesion in the abdominal cavity and a significant reduction in the hyaluronic acid levels in the peritoneal cavity washing lavage. We evaluated the efficacy of cell sheets for preventing leakage of enteral contents in a gastric perforation rat model. Myoblast cell sheets were able to markedly reduce the degree of both intra-abdominal adhesion and inflammation.

Aim The ImmuKnow (IK) assay enables the evaluation of peripheral blood CD4+ adenosine triphosphate activity to facilitate an objective assessment of the cellular immune function in immunosuppressed patients. However, it is unclear whether the IK assay is utilized during the acute postoperative periods following living donor liver transplantation (LDLT). Methods The IK values of 43 LDLT recipients were measured during the month following LDLT to evaluate the relationship between the measured IK values and infectious events. Results The IK values after LDLT were significantly increased compared with the IK values before LDLT ( P

The case involved a 44-year-old man who underwent intersphincteric resection and lateral lymph node dissection for rectal cancer. Pathological diagnosis revealed a well-differentiated adenocarcinoma comprising KRAS wild type, and pT2N0M0 (pathological Stage I). CapeOX (capecitabine plus oxaliplatin[L-OHP]), and bevacizumab therapy was initiated because of local recurrence. Although a partial response (PR) was observed, the therapy was terminated after 6 courses because of the development of hand-foot syndrome. FOLFIRI and cetuximab therapy was initiated after cancer recurrence was observed during a follow up. As the therapeutic efficiency is characterized by stability (stable disease: SD), and the tumor reduction effect observed was not sufficient, we performed an abdominoperineal resection to achieve local control. However, a left hydronephrosis occurred due to the pelvic recurrence, necessitating the emergency hospitalization of the patient. Because resistance to L-OHP was not confirmed, mFOLFOX6 and bevacizumab therapy was introduced in hopes of the effect of the former. As Grade 2 allergy (erythema) appeared immediately after the L-OHP was administered during the 3 courses, treatment was discontinued. We the reinitiated the treatment along with the desensitization therapy from the 4 courses. A total of 27 courses of mFOLFOX6 and bevacizumab therapy were administered until the state of disease progression (progression disease: PD) was determined. PR was defined as the best therapeutic efficiency. In some cases, discontinuation of treatment is necessary as observed in the present case due to the onset of L-OHP allergies, even if the overall effect of the treatment is expected to be good. Our case is essentialas it demonstrates the successfulness of desensitization therapy for L-OHP allergies.

We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%).PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%).Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.

Introduction Laparoscopic colectomy with intracorporeal anastomosis is a minimally invasive surgical procedure for patients with colon cancer. However, there are often concerns about the presence of intraluminal exfoliated malignant cells in the intracorporeal anastomosis. This study investigated the relationship between colon cancer surgery and the incidence of intraluminal exfoliated malignant cells and several factors. Methods Eighty-nine consecutive patients who underwent either laparoscopic or open colectomy were prospectively studied in our department between 2007 and 2011. Before anastomosis, the proximal and distal lumens were irrigated with normal saline and subjected to cytological examination. Results In 27 patients (30.3%), exfoliated cancer cells were detected. On the distal side, the frequency of positive cytology findings of exfoliated malignant cells was significantly lower in the laparoscopic colectomy group than in the open colectomy group (P = 0.01). In the laparoscopic colectomy group, there were no cases of positive cytology findings for exfoliated malignant cells more than 100 mm from the primary tumor. The incidence of positive cytology more than 100 mm from the primary tumor was significantly lower than the incidence of positive cytology less than 100 mm from the primary tumor (P = 0.04). Conclusions Exfoliated malignant cells were detected at anastomosis sites in patients with colon cancer. On the distal side, laparoscopic colectomy may prevent the development of exfoliated malignant cells.

It is well known that the presence of end-stage liver disease increases the risk of developing hepatocellular carcinoma (HCC). Liver transplantation (LT) for patients within the Milan criteria has become a standard treatment for HCC in most developed centers worldwide. However, a major cause of death in cirrhotic patients with HCC after transplantation is tumor recurrence, including peritoneal recurrences, which develops rarely but presents a significant problem with regard to their management. Our experience includes two cases with HCC within the Milan criteria of peritoneal recurrences after living donor LT. Both patients had interventions for HCC in their medical history before LT, and we propose that these might have been a possible cause of the HCC peritoneal recurrence., Case Reports in Gastroenterology, 9(1), pp.29-35; 2015

Introduction Granulosa cell tumors (GCTs) are rare functional sex-cord-stromal ovarian neoplasms characterized by low malignancy potential and late relapse, which rarely metastasize to the liver. Presentation of case A 43-year-old female, who had undergone surgery to treat a GCT of the left ovary in 1976, complained of abdominal distention in May 2001. Imaging studies demonstrated masses in the right lobe of the liver, together with massive ascites. The patient's bloody ascites showed no cytological evidence of malignancy. A diagnostic laparoscopy was performed, and the biopsy specimen was histologically proven to be a recurrent granulosa cell tumor. The patient was successfully treated surgery followed by systemic chemotherapy. Her postoperative course was uneventful and systemic chemotherapy was repeated due to the suspicion of a recurrence in the pelvic cavity. Discussion GCTs which are rare malignant tumors of the ovary, tend to be associated with late recurrence. Although most recurrences occur within 10 years after the initial diagnosis, there are occasional reports of recurrences after 10 years have been. We experienced the rare case of a patient who relapsed 25 years after the initial diagnosis. Conclusion The long natural history of this disease highlights the importance of extended follow up for GCT patients. In addition, aggressive therapy including surgery and chemotherapy may contribute to a patient's long-term prognosis., International Journal of Surgery Case Reports, 12, pp.7-10; 2015

We previously reported that progression of liver cirrhosis is quicker and survival is dismal in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection, especially when acquired in childhood through contaminated blood products. Recently, we performed the first deceased donor liver transplantation (DDLT) for an HIV/HCV-coinfected hemophilic patient in Japan. A 40-year-old man was referred to our hospital for liver transplantation. Regular DDLT was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 465 min, and the graft liver weighed 1,590 g. The antiretroviral therapy (ART) was switched from darunavir/ritonavir to raltegravir before the transplant for flexible usage of calcineurin inhibitors postoperatively; tenofovir was used as the baseline treatment. The postoperative course was uneventful, and the patient was discharged home on day 43. He started receiving anti-HCV treatment on day 110 with pegylated interferon, ribavirin, and simeprevir after the DDLT. Herein, we report the first case of DDLT in Japan. Meticulous management of ART and clotting factors could lead to the success of DDLT., Japanese Journal of Infectious Diseases, 69(1), pp.80-82; 2016

Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density. Primary rat hepatocytes were plated onto TIG-118 cells, previously plated 3 days before at 1.04, 5.21, and 26.1×103 cells/cm2. Hepatocytes plated onto lower TIG-118 cell densities expanded better during the early culture period. The hepatocytes gathered as colonies and only exhibited small adhesion areas because of the pushing force from proliferating TIG-118 cells. The smaller areas of each hepatocyte result in the development of bile canaliculi. The highest density of TIG-118 cells downregulated albumin synthesis activity of hepatocytes. The hepatocytes may have undergone apoptosis associated with high TGF-β1 concentration and necrosis due to a lack of oxygen. These occurrences were supported by apoptotic chromatin condensation and high expression of both proteins HIF-1a and HIF-1b. Three types of engineered hepatocyte/fibroblast sheets comprising different TIG-118 cell densities were harvested after 4 days of hepatocyte culture and showed a complete cell sheet format without any holes. Hepatocyte morphology and liver-specific function levels are controlled by TIG-118 cell density, which helps to design better engineered hepatocytes for future applications such as in vitro cell-based assays and transplantable hepatocyte tissues.

Europe and the United States have high morbidity rates of colorectal cancer, it being the third most common new cancer among both men and women each year. Colorectal cancer morbidity is also high in Japan. Advances in surgery, chemotherapy, and molecular targeted drugs have extended the prognosis of colorectal cancer, although the effects of these treatments remain poor in some patients. Colorectal cancer almost always presents as differentiated adenocarcinoma, although one tissue type, signet-ring cell carcinoma, occurs rarely. Overall, colorectal signet-ring cell carcinoma is very infrequent among cases of colorectal cancer, however, its prognosis is reported as being extremely poor. Several reports have addressed its clinicopathological and typical genetic characteristics, such as mutation of viral oncogene Kirsten rat sarcoma (KRAS) gene, but there have been few comprehensive investigations of its characteristics and genetic background. In this review, we examine features of colorectal signet-ring cell carcinoma by summarizing its clinical and genetic characteristics.

Anastomotic leakage is a serious complication that can occur after colorectal surgery. Several risk factors for anastomotic leakage have been reported based on the findings of prospective and retrospective studies, including patient characteristics, the use of neoadjuvant therapy, the tumor location, intraoperative events, etc. However, as these risk factors affect each other, the statistical results have differed in each study. In addition, differences in surgical methods, including laparoscopy versus laparotomy or stapling anastomosis versus handsewn anastomosis, may influence the incidence of anastomotic leakage. This mini-review summarizes the results of reported papers to clarify the current evidence of risk factors for anastomotic leakage., Surgery Today, 44(9), pp.1595-1602; 2014