Pathologic Complete Response after Chemotherapy with Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma with Tumor Thrombus in the Main Portal Trunk.

We report a case of pathologic complete response after successful treatment for advanced hepatocellular carcinoma (HCC) complicated with portal venous tumor thrombus with atezolizumab and bevacizumab followed by radical resection. The patient was a male in his 60s. During follow-up for chronic hepatitis B, abdominal ultrasonography revealed a huge tumor located in the right lobe of the liver with the portal vein thrombosed by the tumor. The tumor thrombus extended to the proximal side of the left branch of the portal vein. The patient's tumor marker levels were elevated (alpha-phetoprotein, 14,696 ng/mL; PIVKA-II, 2,141 mAU/mL). Liver biopsy revealed poorly differentiated HCC. The lesion was categorized as advanced stage according to the BCLC staging system. As systemic therapy, atezolizumab plus bevacizumab was administered. Imaging showed marked shrinkage of the tumor and portal venous thrombus with a remarkable decrease of tumor marker levels after 2 courses of chemotherapy. After 3 additional courses of chemotherapy, radical resection was considered possible. The patient underwent right hemihepatectomy and portal venous thrombectomy. A pathological examination revealed a complete response. In conclusion, we experienced a case in which advanced HCC was curatively treated with atezolizumab plus bevacizumab, which was administered as systemic therapy with a view to conversion surgery.

Endoscopic mucosal ischemic index for predicting anastomotic complications after esophagectomy: a prospective cohort study.

BACKGROUND: Postoperative complications related to gastric conduit reconstruction are still common issues after McKeown esophagectomy. A novel endoscopic mucosal ischemic index is desired to predict anastomotic complications after McKeown esophagectomy. AIMS AND METHODS: The purpose of this study was to prospectively evaluate the safety and efficacy of endoscopic examinations of the anastomotic region in the acute period after esophagectomy. Endoscopic examinations were performed on postoperative days (PODs) 1 and 8. The severity of ischemia was prospectively validated according to the endoscopic mucosal ischemic index (EMII). RESULTS: A total of 58 patients were included after evaluating the safety and feasibility of the endoscopic examination on POD 1 in 10 patients. Anastomotic leakage occurred in 6 patients. Stricture occurred in 13 patients. A greater than 67% circumference and lesion length greater than 20 mm of anastomotic ischemic area (AIA) on POD 1 were associated with developing anastomotic leakage after esophagectomy (OR: 14.5; 95% CI: 1.8-306.5; P = 0.03, OR: 19.4; 95% CI: 1.7-536.8; P = 0.03). More than 67% circumferential ischemic mucosa and ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were associated with developing anastomotic strictures after esophagectomy (OR: 6.4; 95% CI: 1.4-31.7; P = 0.02, OR: 5.9; 95% CI: 1.2-33.1; P = 0.03). Patients with either more than 67% circumferential ischemic mucosa or ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were defined as EMII-positive patients. The sensitivity, specificity, and positive and negative predictive values of EMII positivity on POD 1 for leakage were 100%, 78.8%, 35.3%, and 100%, respectively. The sensitivity, specificity, and positive and negative predictive values of the EMII positivity on POD 1 for strictures were 69.2%, 82.2%, 52.9%, and 90.2%, respectively. CONCLUSIONS: The application of an endoscopic classification system to mucosal ischemia after McKeown esophagectomy is both appropriate and satisfactory in predicting anastomotic complications. TRIAL REGISTRATION: Clinical Trial.gov Registry, ID: NCT02937389, Registration date: Oct 17, 2015.

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Helicobacter bilis infection induces oxidative stress in and enhances the proliferation of human cholangiocytes.

BACKGROUND: Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H. bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H. bilis on cholangiocytes, focusing on inflammation and oxidative stress. MATERIALS AND METHODS: Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H. bilis infection. RESULTS: Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H. bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4 pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p < .05). MMNK-1 proliferation was also significantly higher in H. bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p < .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H. bilis (1.0 vs. 1.17 ± 0.06, p < .05); however, DNA injury was not observed in cocultures with H. bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/µl, p = .06). CONCLUSIONS: Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.

Risk Factors for Non-Ampullary Duodenal Adenocarcinoma: A Systematic Review.

INTRODUCTION: An increase in the incidence of duodenal adenocarcinoma has been recently reported. However, little is known about the risk factors for duodenal adenocarcinoma, which are important for screening purposes. We, therefore, aimed to conduct a systematic review to identify risk factors for non-ampullary duodenal adenocarcinoma. METHODS: A medical literature search was performed using electronic databases, including PubMed, Cochrane Library, Japan Medical Abstracts Society, and Web of Science. Studies that assessed the association between dietary habits, lifestyle behaviors, comorbidities, and non-ampullary duodenal adenocarcinoma were extracted. The Newcastle-Ottawa Scale was used to assess the risk of bias in individual studies, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the quality of evidence across studies included in this review. RESULTS: Out of 1,244 screened articles, 10 were finally selected for qualitative synthesis. In the general population, no consistent risk factors were identified except for Helicobacter pylori positivity, which was considered a risk factor in 2 studies, but the quality of evidence was considered very low because of the high risk of bias. In patients with familial adenomatous polyposis (FAP), Spigelman stage IV at initial endoscopy was considered a consistent risk factor in 3 studies. CONCLUSIONS: There are currently limited data regarding risk factors for non-ampullary duodenal adenocarcinoma, and no conclusive risk factors were identified in the general population. However, in patients with FAP, Spigelman stage IV was identified as a consistent risk factor. Further studies are needed to improve diagnosis and support effective clinical management of this malignancy.

Highly feasible procedure for laparoscopic transplantation of cell sheets under pneumoperitoneum in porcine model.

INTRODUCTION: Cell sheet technology is one of the most successful methodologies in regenerative medicine. Various applications of cell sheets have been introduced in first-in-human studies in several clinical fields. When transplanting a cell sheet into internal organs, a relatively large incision is required for delivery due to difficulty handling the sheet. We developed a laparoscopic delivery procedure for safe and easy transplantation of cell sheets in a porcine model. METHODS: Pneumoperitoneum was established by inflation with CO2. First, to increase the strength during handling, fibrin was sprayed onto the surface of the cell sheet, and then a myoblast sheet was placed onto the newly developed carrier. The sheets were pinched with laparoscopic forceps to insert into the abdominal cavity through the laparoscopic port. Myoblast sheets were then applied to the surface of the liver, colon, small intestine, and stomach, and procedure times were measured. At three days post transplantation, a histopathological examination was performed to confirm engraftment of the sheet. The function and engraftment were also analyzed in a duodenal endoscopic submucosal dissection (ESD) model. RESULTS: The fibrin-processed myoblast sheet was able to be managed with conventional laparoscopic forceps without breaking. Despite the drastic change in air pressure by passing through the laparoscopic port, the sheets suffered no apparent damage. The transplantation procedure times did not markedly differ among transplant sites. A histopathological examination revealed thin-layered, desmin-positive cells at each transplant site. With transplantation following ESD, the engrafted myoblast sheets effectively prevented delayed perforation. CONCLUSIONS: Our procedure is simple, and the system involves a carrier made of medically fit silicon, commercially available fibrin glue and conventional laparoscopic forceps. Our procedure is a powerful tool for laparoscopical cell sheet transplantation.

Exenatide challenge in oral glucose tolerance test is insufficient for predictions of glucose metabolism and insulin secretion after sleeve gastrectomy (SG) in obese patients with type 2 diabetes: a pilot study to establish a preoperative model to estimate ß-cell function following augmented glucagon-like peptide-1 secretion after SG.

The postoperative increase in glucagon-like peptide-1 (GLP-1) is the main factor to improve glucose metabolism following sleeve gastrectomy (SG) in obese patients with type 2 diabetes. We investigated whether the ß-cell responsiveness to an injection of exogenous GLP-1 in the preoperative period could determine the postoperative glucose tolerance in 18 patients underwent SG. In the preoperative period, a regular oral glucose tolerance test (OGTT) and an exenatide-challenge during OGTT (Ex-OGTT) were performed to evaluate the ß-cell function and its responsiveness to GLP-1. The postoperative glucose tolerance was evaluated by another regular OGTT performed at 3 months after SG. The significant decrease in glucose levels with enhanced secretions of insulin and GLP-1 was observed in OGTT at 3 months after SG. The area under the curve of glucose from 0 to 120 minutes (AUC glucose0-120 min) and the insulinogenic index (I.I.) in OGTT at 3 months post-SG were significantly improved compared to those in preoperative period, but comparable with those in Ex-OGTT. AUC glucose0-120 min and I.I. in OGTT at 3 months post-SG were significantly correlated with not only those in Ex-OGTT, but also those in the preoperative regular OGTT. Conversely, the correlations calculated by the Spearman's ρ were stronger in the latter than the former. This exenatide-challenge protocol might be useful to estimate glucose tolerance and insulin secretion after SG, however, it may be insufficient to improve predictability of a patient who is likely to achieve a significant benefit on glucose metabolism from receiving SG.

Bioengineering of a CLiP-derived tubular biliary-duct-like structure for bile transport in vitro.

The integration of a bile drainage structure into engineered liver tissues is an important issue in the advancement of liver regenerative medicine. Primary biliary cells, which play a vital role in bile metabolite accumulation, are challenging to obtain in vitro because of their low density in the liver. In contrast, large amounts of purified hepatocytes can be easily acquired from rodents. The in vitro chemically induced liver progenitors (CLiPs) from primary mature hepatocytes offer a platform to produce biliary cells abundantly. Here, we generated a functional CLiP-derived tubular bile duct-like structure using the chemical conversion technology. We obtained an integrated tubule-hepatocyte tissue via the direct coculture of hepatocytes on the established tubular biliary-duct-like structure. This integrated tubule-hepatocyte tissue was able to transport the bile, as quantified by the cholyl-lysyl-fluorescein assay, which was not observed in the un-cocultured structure or in the biliary cell monolayer. Furthermore, this in vitro integrated tubule-hepatocyte tissue exhibited an upregulation of hepatic marker genes. Together, these findings demonstrated the efficiency of the CLiP-derived tubular biliary-duct-like structures regarding the accumulation and transport of bile.

Efficacy of endoscopic preventive procedures to reduce delayed adverse events after endoscopic resection of superficial nonampullary duodenal epithelial tumors: a meta-analysis of observational comparative trials.

BACKGROUND AND AIMS: Although various procedures have been used to prevent serious adverse events after endoscopic resection of the duodenum, their effectiveness has not been determined. In this study, we conducted a systematic review and meta-analysis to determine whether endoscopic preventive procedures reduce delayed adverse events. METHODS: Studies on endoscopic treatment for superficial nonampullary duodenal tumors were selected. We compared the following 2 groups: the closure group, which underwent mucosal sutures and coverage of mucosal defects after resection, and the unclosed group, which did not. The primary outcome was the rate of delayed adverse events, including perforation and bleeding. The pooled risk ratios (RRs) of all outcomes investigated, the 95% confidence intervals (CIs), and P values were calculated. RESULTS: A total of 438 patients from 4 studies were included in the meta-analysis. The pooled overall adverse event rates in the closure group and unclosed group were 3.6% and 21.1%, respectively. This rate was significantly lower in the closure group (RR, 0.19; 95% CI, 0.10-0.38; P < .01; I2 = 0%), and the rate of delayed bleeding was significantly lower in the closure group (RR, 0.14; 95% CI, 0.06-0.33; P < .01; I2 = 0%). Regarding delayed perforation, the RR in the closure group was 0.39 (95% CI, 0.12-1.32; P = .13; I2 = 0%). CONCLUSIONS: Preventive procedures significantly reduced the risk of delayed adverse events by more than 80%. After endoscopic resection of the duodenum, the implementation of preventive procedures, including mucosal sutures and coverage of mucosal defects, to delay adverse events is strongly recommended.

Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Although aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer. MATERIALS AND METHODS: This prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia. RESULTS: Twenty women were included (median age 57.5 years; range 55-72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius - 5.3%, p < 0.01; distal tibia - 3.2%, p < 0.01), Tb.vBMD (- 3.2%, p < 0.01; - 1.0%, p < 0.05, respectively), and Ct.vBMD (- 3.2%, p < 0.01; - 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  - 0.53, r =  - 0.47, respectively) CONCLUSION: Postmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.

Chemical conversion of aged hepatocytes into bipotent liver progenitor cells.

AIM: In the aging society, understanding the influence of hepatocyte age on hepatocyte donation may inform efforts to expand alternative cell sources to mitigate liver donor shortage. A combination of the molecules Y27632, A-83-01, and CHIR99021 has been used to reprogram rodent young hepatocytes into chemically induced liver progenitor (CLiP) cells; however, whether it could also reprogram aged hepatocytes has not yet been elucidated. METHODS: Primary hepatocytes were isolated from aged and young donor rats, respectively. Hepatic histological changes were evaluated. Differences in gene expression in hepatocytes were identified. The in vitro reprogramming plasticity of hepatocytes as evidenced by CLiP conversion and the hepatocyte and cholangiocyte maturation capacity of reprogrammed CLIPs were analyzed. The effect of hepatocyte growth factor (HGF) on cell propagation was also investigated. RESULTS: The histological findings revealed ongoing liver damage with inflammation, fibrosis, senescence, and ductular reaction in aged livers. Microarray analysis showed altered gene expression profiles in hepatocytes from aged donors, especially with regard to metabolic pathways. Aged hepatocytes could be converted into CLiPs (Aged-CLiPs) expressing progenitor cell markers, but with a relatively low proliferative rate compared with young hepatocytes. Aged-CLiPs possessed both hepatocyte and cholangiocyte maturation capacity. HGF facilitated CLiP conversion in aged hepatocytes, which was partly related to the activation of Erk1 and Akt1 signaling. CONCLUSIONS: Aged rat hepatocytes have retained reprogramming plasticity as evidenced by CLiP conversion in culture. HGF promoted proliferation and CLiP conversion in aged hepatocytes. Hepatocytes from aged donors may be used as an alternative cell source to mitigate donor shortage.

The incidence of non-ampullary duodenal cancer in Japan: The first analysis of a national cancer registry.

BACKGROUND AND AIM: Although duodenal cancer is rare, no epidemiological research on this disease has been conducted in Asian countries. We aimed to elucidate the incidence and clinical features of duodenal cancer in Japan using a large-scale national database. METHODS: Data of patients with primary duodenal cancer diagnosed from January 1, 2016, to December 31, 2016, were extracted from the Japanese national cancer registry. Excluding malignant neoplasm of the Vater's ampulla, we calculated the incidence among the population as a crude number of patients with duodenal cancer divided by the total Japanese population in 2016. We performed multivariate analyses using logistic regression models to identify risk factors for advanced cancer, defined as metastatic cancer or local invasion to adjacent organs. RESULTS: Data on 3005 patients were included. The incidence of duodenal cancer was 23.7 per 1 000 000 person-years. In total, 56.4% of cases were detected at the localized stage. In the localized cancer group, endoscopic resection was more frequently performed (48.0%), whereas in the advanced cancer group, surgery and chemotherapy were the major treatment options (39.3% and 41.5%, respectively). Multivariate analyses identified age ≥80 years (odds ratio [OR], 1.489; 95% confidence interval [CI], 1.113-1.992; P = 0.007), incidental detection (OR, 2.325; CI, 1.623-3.331; P < 0.0001), and precise examination for symptomatic patients (OR, 10.561; CI, 7.416-15.042; P < 0.0001) as independent risk factors for advanced cancer. CONCLUSIONS: Our study revealed the incidence of duodenal cancer in Japan. However, localized cancer was the major tumor stage at detection, resulting in a high rate of endoscopic resection.

Changes in the Role and Mode of Liver Resection for Hepatocellular Carcinoma Over 20 Years: A Single-Center Analysis.

INTRODUCTION: The aim of this study was to analyze changes in characteristics of HCC and the modes of LR over 20 years in order to show the impact of those changes in the outcome of LR. In addition, BCLC staging was used to assess the limitations of this classification system and changes over the decade. PATIENTS AND METHODS: In our department, 500 liver resections (LR) were performed for hepatocellular carcinoma (HCC) over the 20 years between January 2000 and February 2020. The 208 cases performed through 2009 were designated as Era 1, and the 292 cases between 2010 and February 2020 were termed Era 2. We analyzed changes in the characteristics of HCC and mode of LR (Study 1), and final outcomes of LR are shown according to the BCLC staging classifications and eras using data from the 5 years after LR (Study 2). RESULTS: In Era 1, the mean age of the patients was 68, while in Era 2 the mean age was 71, which was significantly older than the patients in Era 1. HCC that developed from non-B, non-C liver cirrhosis was significantly increased in Era 2 (45%) as compared to that in Era 1 (34%). Laboratory data were all comparable between the eras in patients undergoing LR for HCC. The size and numbers of the HCC as well as tumor markers were similar between the eras. As to the mode of LR, although the extent of LR was similar between the eras, the laparoscopic method was significantly increased in Era 2. Blood loss was significantly lower in Era 2 (mean 519 g) than in Era 1 (1,085 g). Patient survival and recurrence-free survival (RFS) were similar between the two eras, while RFS at 5 years after LR was better in Era 2. Even in the BCLC A category, only patients with a single HCC less than 5 cm showed best results, while patients with HCC within the rest of BCLC A and BCLC B showed a dismal outcome. There was no difference in OS and RFS between the eras after stratification by BCLC. CONCLUSION: There are conspicuous changes in the baseline characteristics and mode of LR over 20 years, which should be taken into account for patient care and informed consent for patients undergoing LR going forward.

Limited resection vs. pancreaticoduodenectomy for primary duodenal adenocarcinoma: a systematic review and meta-analysis.

It is well known that surgery is the mainstay treatment for duodenal adenocarcinoma. However, the optimal extent of surgery is still under debate. We aimed to systematically review and perform a meta-analysis of limited resection (LR) and pancreatoduodenectomy for patients with duodenal adenocarcinoma. A systematic electronic database search of the literature was performed using PubMed and the Cochrane Library. All studies comparing LR and pancreatoduodenectomy for patients with duodenal adenocarcinoma were selected. Long-term overall survival was considered as the primary outcome, and perioperative morbidity and mortality as the secondary outcomes. Fifteen studies with a total of 3166 patients were analyzed; 995 and 1498 patients were treated with limited resection and pancreatoduodenectomy, respectively. Eight and 7 studies scored a low and intermediate risk of publication bias, respectively. The LR group had a more favorable result than the pancreatoduodenectomy group in overall morbidity (odd ratio [OR]: 0.33, 95% confidence interval [CI] 0.17-0.65) and postoperative pancreatic fistula (OR: 0.13, 95% CI 0.04-0.43). Mortality (OR: 0.96, 95% CI 0.70-1.33) and overall survival (OR: 0.61, 95% CI 0.33-1.13) were not significantly different between the two groups, although comparison of the two groups stratified by prognostic factors, such as T categories, was not possible due to a lack of detailed data. LR showed long-term outcomes equivalent to those of pancreatoduodenectomy, while the perioperative morbidity rates were lower. LR could be an option for selected duodenal adenocarcinoma patients with appropriate location or depth of invasion, although further studies are required.

Establishment of an in-vivo porcine delayed perforation model after duodenal endoscopic submucosal dissection.

OBJECTIVES: Duodenal endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal epithelial tumors has a significant incidence rate of delayed perforation. Although several methods have been proposed to prevent delayed perforation, the most appropriate methods remain unclear. Currently, there is no appropriate animal model to validate methods for preventing duodenal delayed perforation. This study aimed to establish an in-vivo porcine delayed perforation model after duodenal submucosal dissection. METHODS: Two porcine models underwent either ESD or surgical submucosal dissection. In the surgical dissection model, an inverted duodenal mucosa was resected with electrosurgical energy. In the ESD model, a gauze was placed behind the duodenum with grasped transverse part to improve endoscopic maneuverability. The mucosal defects after dissection were treated with omental coverage without suture in both models. All models were euthanized 0-5 days after procedure. Body weight; resection size; procedure dissection time; presence of intraoperative perforation and delayed perforation; and adhesion score were assessed. RESULTS: There were no significant differences in body weight and adhesion score between the two models. Resection size was significantly larger in the surgical dissection models than in the ESD models (19 mm vs 14.3 mm, P < 0.01). Procedure time was significantly longer in the ESD models than in the surgical models (45.2 minutes vs 4.5 minutes, P < 0.01). Delayed perforation rates in the surgical dissection models and the ESD models were 0% (0/5) and 100% (5/5), respectively (P < 0.01). CONCLUSIONS: This study indicated that our in-vivo porcine duodenal ESD model is beneficial to evaluate a prevention strategy for delayed perforation.

[A Case of Unresectable Gastric Cancer with Paraaortic Lymph Node Metastasis Treated with Conversion Therapy].

We present a case of advanced gastric cancer with paraaortic lymph node metastasis successfully treated by conversion therapy. The patient was a 71‒year‒old male. Because of paraaortic lymph node metastasis, we initiated intensive chemotherapy with S‒1, oxaliplatin, and trastuzumab. After 6 courses, CT examination revealed that the size of the primary tumor decreased, suggesting a complete response(CR). Furthermore, the metastatic lymph nodes decreased in both number and size, suggesting a partial response(PR). We continued chemotherapy, changing to S‒1 and trastuzumab only because of Grade 3 neutropenia, and conducted continuous infusion chemotherapy. After 5 courses, we performed an upper gastrointestinal endoscopy. The primary tumor recurred, suggesting a progressive disease(PD), while metastasis to the paraaortic lymph nodes disappeared. We decided that a curative resection was possible and performed distal gastrectomy with D2 and paraaortic lymph node dissection. The postoperative courses were uneventful, and the patient was discharged from the hospital 12 days postoperation. The patient is well without any recurrence of cancer at 1 year 3 months postoperation. Conversion therapy may offer the possibility of prolonged survival for patients with gastric cancer previously considered unresectable.

Study Protocol for Assessing the Efficacy of Compression Therapy Using Stockings and Sleeves to Prevent Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients.

Taxanes are key drugs for patients with breast cancer. A major adverse effect associated with the administration of the taxane docetaxel is chemotherapy-induced peripheral neuropathy (CIPN). We are conducting a singlecenter, single-arm, open-label historical control trial to evaluate the ability of compression therapy using stockings or sleeves to prevent CIPN due to docetaxel treatment. The primary endpoint is the incidence of all-grade CIPN according to patients' records until 3 weeks after the fourth docetaxel administration. This study's results will clarify whether compression therapy using stockings or sleeves can prevent CIPN in breast cancer patients.

The Efficacy of Software to Help Patients Understand Drug for Adjuvant Treatment for Breast Cancer: A Pilot Randomized Controlled Trial.

We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants' understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients' perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs.

Packing procedure effective for liver transplantation in hemophilic patients with HIV/HCV coinfection.

We herein report an effective procedure for liver transplantation (LT) for severe cirrhotic patients with hemophilia. Three hemophilic patients suffering from liver cirrhosis due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection underwent deceased donor LT in our institute. Basic clotting parameters were measured and evaluated during LT to determine the optimal packing procedure. All patients were treated with a gauze packing procedure to ensure stable hemostasis in relation to hemophilia during the peri-transplant period. The graft function of all patients recovered well upon gauze removal (depacking) procedure and the patients were finally discharged to home. The administration of clotting factor was discontinued on day 3 after deceased donor LT. No infectious complications occurred in any of the 3 patients. This technique could be an option for achieving successful LT in these patients. Cooperation between transplant surgeons and anesthesiologists can make this challenging operation possible.