Homologous recombination contributes to the repair of acetaldehyde-induced DNA damage.

Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g. in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions among biological substances including DNA, RNA, and protein, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we explored mechanisms involved in the repair of acetaldehyde-induced DNA damage by examining the cellular sensitivity to acetaldehyde in the collection of human TK6 mutant deficient in each genome maintenance system. Among the mutants, mismatch repair mutants did not show hypersensitivity to acetaldehyde, while mutants deficient in base and nucleotide excision repair pathways or homologous recombination (HR) exhibited higher sensitivity to acetaldehyde than did wild-type cells. We found that acetaldehyde-induced RAD51 foci representing HR intermediates were prolonged in HR-deficient cells. These results indicate a pivotal role of HR in the repair of acetaldehyde-induced DNA damage. These results suggest that acetaldehyde causes complex DNA damages that require various types of repair pathways. Mutants deficient in the removal of protein adducts from DNA ends such as TDP1-/- and TDP2-/- cells exhibited hypersensitivity to acetaldehyde. Strikingly, the double mutant deficient in both TDP1 and RAD54 showed similar sensitivity to each single mutant. This epistatic relationship between TDP1-/- and RAD54-/- suggests that the protein-DNA adducts generated by acetaldehyde need to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of the genotoxic and mutagenic effects of acetaldehyde.

Development of predictive score for postoperative dysphagia after emergency abdominal surgery in patients of advanced age.

Aim: Postoperative dysphagia after emergency abdominal surgery (EAS) in patients of advanced age has become problematic, and appropriate dysphagia management is needed. This study was performed to identify predictive factors of dysphagia after EAS and to explore the usefulness of swallowing screening tools (SSTs). Methods: This retrospective study included 267 patients of advanced age who underwent EAS from 2012 to 2022. They were assigned to a dysphagia group and non-dysphagia group using the Food Intake Level Scale (FILS) (dysphagia was defined as a FILS level of <7 on postoperative day 10). From 2018, original SSTs including a modified water swallowing test were performed by nurses. Results: The incidence of postoperative dysphagia was 22.8% (61/267). Patients were significantly older in the dysphagia than non-dysphagia group. The proportions of patients who had poor nutrition, cerebrovascular disorder, Parkinson's disease, dementia, nursing-care service, high intramuscular adipose tissue content (IMAC), and postoperative ventilator management were much higher in the dysphagia than non-dysphagia group. Using logistic regression analysis, high IMAC, postoperative ventilator management, cerebrovascular disorder, and dementia were correlated with postoperative dysphagia and were assigned 10, 4, 3, and 3 points, respectively, according to each odds ratio. The optimal cut-off value was 7 according to a receiver operating characteristics curve. Using 1:1 propensity score matching for high-risk patients, the incidence of postoperative dysphagia was reduced by SSTs. Conclusions: The new prediction score obtained from this study can identify older patients at high risk for dysphagia after EAS, and SSTs may improve these patients' short-term outcomes.

Cachexia index as a prognostic predictor after resection of pancreatic ductal adenocarcinoma.

Aim: This study was performed to investigate the relationship between the preoperative cachexia index (CXI) and long-term outcomes in patients who have undergone radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 144 patients who underwent pancreatic resection for treatment of PDAC were retrospectively analyzed. The relationship between the CXI and the patients' long-term outcomes after PDAC resection was investigated. The CXI was calculated based on the preoperative skeletal muscle index, serum albumin level, and neutrophil-to-lymphocyte ratio. After propensity-score matching, we compared clinicopathological features and outcomes. Results: The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.16-3.23; P = 0.0118), R1 resection (HR, 57.20; 95% CI, 9.39-348.30; P < 0.0001), and a low CXI (HR, 2.10; 95% CI, 1.27-3.46; P = 0.0038) were independent and significant predictors of disease-free survival (DFS) after PDAC resection. Moreover, a low CXI (HR, 3.14; 95% CI, 1.71-5.75; P = 0.0002) was an independent and significant predictor of overall survival (OS) after PDAC resection. After propensity-score matching, the low CXI group had a significantly worse prognosis than the high CXI group for both DFS and OS. Conclusion: The CXI can be a useful prognostic factor for DFS and OS after pancreatic resection for treatment of PDAC.

[A 30-Month Survival Case of Undifferentiated Carcinoma of the Duodenum Treated by Pancreaticoduodenectomy].

The patient was an elderly man in his early 80s who was admitted to our hospital due to anemia and tarry stools. An upper gastrointestinal endoscopy revealed a type 2 tumor in the second portion of the duodenum. An endoscopic biopsy revealed poorly differentiated adenocarcinoma. We performed a pancreaticoduodenectomy because neither lymphadenopathy nor distant metastases were found. Macroscopic findings revealed that the lesion was mainly in the second portion of the duodenum, and there was no evidence of invasion of the main pancreatic duct, the bile duct, or the ampulla of Vater. Histologically, the tumor was composed of atypical cells with polymorphic or spindle-shaped nuclei proliferating in a scattered fashion, and immunohistological examinations showed weakly positive results for cytokeratin(CK)AE1/AE3 and CK20 and positive results for vimentin but negative results for CK7. The tumor was diagnosed as undifferentiated carcinoma of the duodenum(pT4N0M0, pStage ⅡB). The patient recovered enough to be discharged and was followed up without postoperative adjuvant chemotherapy. He maintained recurrence-free survival for 27 months, after which lymph node and lung metastases reoccurred. This is a rare case of undifferentiated carcinoma of the duodenum treated by curative resection with a relatively favorable prognosis.

Effect of Early Enteral Nutrition on Graft Loss After Living Donor Liver Transplantation: A Propensity Score Matching Analysis.

BACKGROUND: This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT. METHODS: We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss. RESULTS: The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P = .067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P = .12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P = .034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P = .43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P = .038). CONCLUSION: Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis.

Textbook outcome in the laparoscopic cholecystectomy of acute cholecystitis.

PURPOSE: Textbook outcome (TO) is a novel composite measure of clinical outcomes that can be used to measure the quality of surgical outcomes. The aim of this cohort study was to propose TO criteria for laparoscopic cholecystectomy for acute cholecystitis and to identify reasons for TO failure and individual patient factors that predispose to failure. METHODS: We retrospectively analyzed data for 189 patients with acute cholecystitis who underwent laparoscopic cholecystectomy. TO was defined as laparoscopic cholecystectomy without conversion to open cholecystectomy, intraoperative complications, postoperative complications (Clavien-Dindo classification ≥2), prolonged length of stay (≥10 days), readmission within 30 days, or mortality. RESULTS: TO was achieved in 154 of 189 patients who underwent laparoscopic cholecystectomy for acute cholecystitis. Medical costs were lower in the TO-achieved group than in the TO-failure group. Factors associated with TO failure on multivariate analysis were age > 70 years, hemoglobin <11.9 g/dL, and white blood cells >18 000 / µL (all P < .05). CONCLUSIONS: Applying TO to patients with acute cholecystitis allowed us to evaluate the overall quality of care related to hospitalization. TO may provide better assessment of the quality of care and help determine the treatment choice and reduce costs.

Cdc7 kinase is required for postnatal brain development.

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7Fl/Fl NestinCre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7Fl/F l NestinCre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.

Safety of laparoscopic cholecystectomy in patients with a cerebrospinal fluid shunt in the peritoneal cavity.

INTRODUCTION: The management of patients with a cerebrospinal fluid (CSF) shunt located in the peritoneal cavity undergoing laparoscopic surgery is an issue that has not yet been settled. These patients are at risk of increased intracranial pressure caused by peritoneal insufflation, shunt dysfunction, and shunt infection/retrograde meningitis. This study aimed to determine the need for perioperative shunt intervention in CSF shunt patients undergoing laparoscopic cholecystectomy. METHODS: We reviewed and analyzed five shunt patients who underwent laparoscopic cholecystectomy in our institution between 2012 and 2022, as well as 17 patients described in previous reports. RESULTS: Among the 22 patients, shunt type was ventriculoperitoneal in 14 and lumboperitoneal in eight. The most common indication for CSF shunt was hydrocephalus caused by cerebral vascular accident (50.0%). Laparoscopic cholecystectomy was performed for cholecystolithiasis in 13 patients (59.1%), acute cholecystitis in eight (36.4%), and gallbladder polyp in one (4.5%). Shunt clamping or externalization was performed in six patients. Two patients in the group that did not undergo shunt clamping or externalization experienced complications (intra abdominal abscess and subcutaneous emphysema). However, the incidence of short-term complications (both overall and shunt-related) and median length of hospital stay did not significantly differ between the two groups. CONCLUSION: Routine shunt clamping, externalization, or removal might not be necessarily required in patients with a ventriculoperitoneal or lumboperitoneal shunt undergoing laparoscopic cholecystectomy.

Successful laparoscopic cholecystectomy for gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis: a case report.

BACKGROUND: Patients on long-term dialysis are prone to hemorrhagic complications, particularly uremic bleeding, but gallbladder hemorrhage is rare, even in patients on dialysis. There have been occasional reports of a Dieulafoy lesion being a cause of gastrointestinal hemorrhage, but its occurrence within the gallbladder is quite rare. This report describes a case of gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis that was diagnosed early and successfully treated by laparoscopic cholecystectomy. CASE PRESENTATION: The patient was a 68-year-old woman on long-term hemodialysis with end-stage renal failure who presented with epigastralgia and back pain. There was no history of trauma or oral administration of antiplatelet or anticoagulant agents. There were no signs of an inflammatory reaction or hyperbilirubinemia. Contrast-enhanced computed tomography revealed a slightly hyperdense area in the distended gallbladder and extravasation within the gallbladder lumen but no gallstones. A severe atherosclerotic lesion was also found. She was diagnosed to have gallbladder hemorrhage and emergency laparoscopic cholecystectomy was performed. Although the postoperative course was complicated by drug fever, she was discharged on postoperative day 10 in a satisfactory condition. Histology revealed hemorrhagic ulceration with an exposed blood vessel accompanied by abnormal arteries in the submucosa. Arteriosclerosis with eccentric intimal hyperplasia in a small-sized artery was also seen. The diagnosis was gallbladder hemorrhage from a Dieulafoy lesion. CONCLUSIONS: A Dieulafoy lesion should be kept in mind as a cause of gallbladder hemorrhage in a patient with severe arteriosclerosis and a bleeding diathesis, particularly if on dialysis, and treated as early as possible.

Prognostic Impact of the Preoperative Systemic Inflammation Score in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUD: The systemic inflammation score (SIS), which is based on the preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb) level, is a prognostic indicator for several cancer types. However, the prognostic significance of the SIS in pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Seventy-eight patients who underwent radical surgery for PDAC were categorized as follows: SIS 0 (LMR ≥3.51 and Alb ≥4.0 g/dl), n = 26; SIS 1 (LMR <3.51 or Alb <4.0 g/dl), n = 29 and SIS 2 (LMR <3.51 and Alb <4.0 g/dl), n=23. RESULTS: The tumour size sequentially increased in SIS 0, 1 and 2 groups. A higher SIS was associated with increased vascular invasion, perineural invasion and surgical margin positivity rate. Recurrence-free survival (RFS) rates between the SIS 1 and 2 groups showed no significant difference However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for RFS. Overall survival (OS) rates between the SIS 1 and 2 groups also showed no significant difference. However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for OS. The SIS was an independent prognostic factor for RFS and OS. DISCUSSION: The SIS is a simplified prognostic factor for patients with PDAC.

Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer.

BACKGROUND/AIM: Peritoneal metastasis (PM) of gastric cancer (GC) leads to poor clinical outcomes. Tumor-derived exosomes promote metastasis via communication between tumor cells and host cells. In this study, we investigated the effect of Rab27, which is required for exosome secretion, on the PM of GC. MATERIALS AND METHODS: We established a stable knockdown of two Rab27 homologs, Rab27a and Rab27b, in human GC cells (58As9) with a high potential of PM. We examined the level of exosome secretion from Rab27-knockdown 58As9 cells by Western blotting and the ability of Rab27b knockdown to suppress PM in 58As9 cells using a mouse xenograft model. In vitro proliferation and invasion assays were performed in the Rab27b-knockdown cells. Next, Rab27b expression was evaluated in human GC tissues by immunohistochemistry. Finally, we assessed the clinicopathological and prognostic significance of Rab27b expression by RT-qPCR in both our and other TCGA datasets of GC. RESULTS: Rab27a and Rab27b knockdown in 58As9 cells decreased the secretion of exosomes, characterized by the endocytic marker CD63. Rab27b knockdown decreased PM in vivo without affecting the in vitro proliferation or invasion ability of 58As9 cells. In human GC tissues, Rab27b was overexpressed in tumor cells. The overall and recurrence-free survival rates were significantly lower in GC patients with high compared to low Rab27b mRNA expression in our and other TCGA datasets. CONCLUSION: Rab27b expression potentially serves as a poor prognostic biomarker, possibly affecting PM via exosome secretion from GC cells.

Prognostic Impact of Lymphocyte-to-C-Reactive Protein Ratio in Patients Who Underwent Surgical Resection for Pancreatic Cancer.

BACKGROUND: Increasing evidence indicates that increased systemic inflammation is correlated with poorer cancer-specific survival in various cancer types. This study aimed to evaluate the prognostic value of various combinations of inflammatory factors in patients who underwent surgical resection for pancreatic cancer (PC). METHODS: We retrospectively analyzed 97 consecutive patients with PC who underwent pancreatectomy. We assessed the predictive impact for recurrence using a combination of 5 inflammatory markers and focused on the lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: Low preoperative LCR was correlated with low serum hemoglobin, low serum albumin concentration, high frequency of microscopic vascular invasion, and high frequency of microscopic perineural invasion. The low LCR group had significantly worse RFS and OS. Lower preoperative LCR was an independent predictor of shorter RFS and OS in this cohort. DISCUSSION: Preoperative LCR is a novel and convenient prognostic marker for patients with PC. Patients with low LCR may require more favorable intensive therapy.

Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma.

Background and Aim: The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. Methods: Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. Results: The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. Conclusion: This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.

Simple systemic index associated with oxaliplatin-induced liver damage can be a novel biomarker to predict prognosis after resection of colorectal liver metastasis.

Aim: Oxaliplatin, an anticancer drug for advanced colorectal cancer, causes liver sinusoidal damage, sometimes with portal hypertension. We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM). Methods: In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy-associated liver damage on the prognosis was examined. Results: Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL). In a comparison of the BL group (n = 26) and non-BL group (n = 132), patients in the BL group had a significantly lower serum albumin concentration and a significantly higher indocyanine green test result, aspartate aminotransferase-to-platelet ratio index (APRI), and FIB-4 score. Operative morbidities were not significantly different between the two groups. The overall survival rate after hepatectomy was significantly worse in the BL group than in the non-BL group. In the univariate analysis, the serum albumin concentration, indocyanine green test, a high tumor burden score (TBS), and the APRI were statistically significant poor prognostic factors. In the multivariate analysis, the APRI and a high TBS were independent poor prognostic factors. Conclusion: The APRI and TBS in patients with CRLM are prognostic predictors after hepatectomy for metastatic liver cancer. This study indicated that liver damage in patients treated with preoperative oxaliplatin has an effect on the prognosis.

Phosphacan acts as a repulsive cue in murine and rat cerebellar granule cells in a TAG-1/GD3 rafts-dependent manner.

Phosphacan, a chondroitin sulfate proteoglycan, is a repulsive cue of cerebellar granule cells. This study aims to explore the molecular mechanism. The glycosylphosphatidylinositol-anchored neural adhesion molecule TAG-1 is a binding partner of phosphacan, suggesting that the repulsive effect of phosphacan is possibly because of its interaction with TAG-1. The repulsive effect was greatly reduced on primary cerebellar granule cells of TAG-1-deficient mice. Surface plasmon resonance analysis confirmed the direct interaction of TAG-1 with chondroitin sulfate C. On postnatal days 1, 4, 7, 11, 15, and 20 and in adulthood, phosphacan was present in the molecular layer and internal granular layer, but not in the external granular layer. In contrast, transient TAG-1 expression was observed exclusively within the premigratory zone of the external granular layer on postnatal days 1, 4, 7, and 11. Boyden chamber cell migration assay demonstrated that phosphacan exerted its repulsive effect on the spontaneous and brain-derived neurotrophic factor (BDNF)-induced migration of cerebellar granule cells. The BDNF-induced migration was inhibited by MK-2206, an Akt inhibitor. The pre-treatment with a raft-disrupting agent, methyl-ß-cyclodextrin, also inhibited the BDNF-induced migration, suggesting that lipid rafts are involved in the migration of cerebellar granule cells. In primary cerebellar granule cells obtained on postnatal day 7 and cultured for 7 days, the ganglioside GD3 and TAG-1 preferentially localized in the cell body, whereas the ganglioside GD1b and NB-3 localized in not only the cell body but also neurites. Pre-treatment with the anti-GD3 antibody R24, but not the anti-GD1b antibody GGR12, inhibited the spontaneous and BDNF-induced migration, and attenuated BDNF-induced Akt activation. These findings suggest that phosphacan is responsible for the repulsion of TAG-1-expressing cerebellar granule cells via GD3 rafts to attenuate BDNF-induced migration signaling.

Delayed laparoscopic cholecystectomy for a patient with coronavirus disease 2019 who developed gangrenous cholecystitis: a case report.

BACKGROUND: Gangrenous cholecystitis has a high risk of perforation and sepsis; therefore, cholecystectomy in the early stage of the disease is recommended. However, during the novel coronavirus disease 2019 (COVID-19) pandemic, the management of emergent surgeries changed to avoid contagion exposure among medical workers and poor postoperative outcomes. CASE PRESENTATION: A 56-year-old man presented to our hospital with abdominal pain. Computed tomography revealed intraluminal membranes, an irregular or absent wall, and an abscess of the gallbladder, indicating acute gangrenous cholecystitis. Early laparoscopic cholecystectomy seemed to be indicated; however, a COVID-19 antigen test was positive despite no obvious pneumonia on chest computed tomography and no symptoms. After discussion among the multidisciplinary team, antibiotic therapy was started and percutaneous transhepatic gallbladder drainage (PTGBD) was planned for the following day because the patient's vital signs were stable and his abdominal pain was localized. Fortunately, the antibiotic therapy was very effective, and PTGBD was not needed. The cholecystitis improved and the patient was discharged from the hospital on day 10. One month later, laparoscopic delayed cholecystectomy was performed after confirming a negative COVID-19 polymerase chain reaction test result. The postoperative course was uneventful, and the patient was discharged on postoperative day 2 in satisfactory condition. CONCLUSION: We have reported a case of acute gangrenous cholecystitis in a patient with asymptomatic COVID-19 disease. This report can help to determine treatment strategies for patients with gangrenous cholecystitis during future pandemics.

A case of successful conversion surgery for locally advanced pancreatic cancer with synchronous triple cancer of the lung and esophagus: a case report.

BACKGROUND: The number of reports of multiple primary cancer (MPC) is increasing because of the advancement in diagnostic imaging technology. However, the treatment strategy for MPCs involving pancreatic cancer is controversial because of the extremely poor prognosis. We herein report a patient with synchronous triple cancer involving the pancreas, esophagus, and lung who underwent conversion surgery after intensive chemotherapy for unresectable locally advanced pancreatic cancer. CASE PRESENTATION: A 59-year-old man was admitted to our hospital with epigastric pain, anorexia, and weight loss. Computed tomography and upper gastrointestinal endoscopy revealed that the patient had synchronous triple cancer of the pancreas, esophagus, and lung. While the esophageal and lung cancer were relatively non-progressive, the pancreatic tail cancer had invaded the aorta, celiac axis, and left kidney, and the patient was diagnosed with unresectable locally advanced disease. Because the described lesion could have been the prognostic determinant for this patient, we initiated intensive chemotherapy (gemcitabine plus nab-paclitaxel) for pancreatic cancer. After six courses of chemotherapy, the tumor size shrank remarkably and no invasion to the aorta or celiac axis was observed. No significant changes were observed in the esophageal and lung cancers; endoscopic submucosal dissection could be still a curative treatment for the esophageal cancer. Therefore, we performed curative resection for pancreatic cancer (distal pancreatomy, splenectomy, and left nephrectomy; ypT3N0cM0, ypStage IIA, UICC 8th). Pathologically, complete resection was achieved. The patient then underwent endoscopic submucosal dissection for early esophageal cancer (pT1a[M]-LPM) and video-assisted thoracoscopic right upper lobectomy in combination with right lower partial resection for early lung cancer (pT2aN0M0, pStage IB, UICC 8th). Eight months after pancreatic cancer surgery, the patient is alive and has no sign of recurrence; as a result of the successful treatment, the patient has a good quality of life. CONCLUSIONS: Treatment of MPC is challenging, especially for cases with unresectable tumors. Although synchronous triple cancer can involve unresectable pancreatic cancer, radical resection may be possible after careful assessment of the appropriate treatment strategy and downstaging of unresectable tumors.

Laparoscopic delayed and interval appendectomy in the workstyle reform era.

PURPOSE: Excessive working hours have been reported to contribute to burnout among surgeons. In Japan, work-style reform is a problem that needs immediate attention. Acute appendectomy, which often occurs at nighttime, is one of the most common emergency surgeries. The feasibility of delayed and interval appendectomy remains to be investigated. METHODS: Two hundred forty-five consecutive patients who underwent laparoscopic appendectomy in our hospital were enrolled. They were divided into three groups: emergency appendectomy (immediate surgery, soon after the diagnosis [EA group], n = 153), delayed appendectomy (surgery during daytime the following day [DA group], n = 38) and interval appendectomy (antibiotics treatment followed by selective surgery three to four months later [IA group], n = 54). The clinical background and surgical outcomes were compared. Next, the residents' excess working time per month was calculated. RESULTS: The surgical outcomes (operation time, blood loss, length of hospital stay, postoperative complications) were similar between the EA and DA groups. However, no DA was performed during nighttime hours whereas 15.7% of EA was performed during nighttime hours (p = 0.0007). The surgical outcomes of the IA group were also comparable. The residents' excess working time declined following the introduction of DA and workstyle reform. CONCLUSION: Delayed and interval laparoscopic appendectomy are feasible, and can be performed to promote workstyle reform without impairing patient safety.

Indocyanine green fluorescence to ensure perfusion in middle segment-preserving pancreatectomy: a case report.

BACKGROUND: Middle segment-preserving pancreatectomy (MSPP) is an alternative to total pancreatectomy that allows for the preservation of the endocrine and exocrine functions of the pancreas. However, maintaining perfusion to the pancreatic remnant is of critical importance. We describe the first case to our knowledge in which indocyanine green (ICG) fluorescence was used to confirm perfusion to the pancreatic remnant during MSPP. CASE PRESENTATION: A 79-year-old man with diabetes mellitus was referred to our hospital for treatment of a pancreatic tumor. Computed tomography revealed a hypovascular mass in the uncus of the pancreas and dilatation of the main pancreatic duct, measuring 13 mm in the tail of the pancreas. He was diagnosed with cancer of the pancreatic uncus via endoscopic ultrasound and fine-needle aspiration revealed a mixed-type intraductal papillary mucinous neoplasm (IPMN), along with high-risk stigmata in the tail of the pancreas. We performed MSPP and the length of the pancreatic remnant was 4.6 cm. The dorsal pancreatic artery was preserved and perfusion to the pancreatic remnant was confirmed by ICG fluorescence. Histopathological examination showed a pancreatic ductal adenocarcinoma in the uncus (pT1cN1M0, pStage 2B) and IPMN in the tail of the pancreas. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. The patient was transferred to a hospital 33 days after surgery. Insulin administration was necessary, but C-peptide was detectable and blood glucose was relatively well-controlled. He did not exhibit any exocrine dysfunction when pancreatic enzyme supplementation was administered. CONCLUSION: ICG fluorescence can be used to evaluate perfusion to the pancreatic remnant during MSPP.

Impact of a 7.5-Fr Pancreatic Stent for Preventing Pancreatic Fistula after Pancreaticoduodenectomy.

INTRODUCTION: Pancreatic duct stents are widely used to reduce the incidence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD); however, small stents may cause adverse effects, such as occlusion. Recently, we have tried placing a 7.5-Fr pancreatic duct stent to achieve more effective exocrine output from the pancreas; however, the association between pancreatic duct stent size and POPF remains unknown. METHODS: Sixty-five patients with soft pancreatic texture who underwent PD were retrospectively analyzed. After dividing the pancreas, a pancreatic duct stent (stent size 4.0 in 29 patients, 5.0 in 18, and 7.5 Fr in 18) was placed in the main pancreatic duct. RESULTS: Twenty-five of 65 patients with soft pancreatic texture (38.5%) developed POPF. POPF became less frequent as the pancreatic duct stent size increased (p = 0.003). The factors associated with POPF development were a 7.5-Fr pancreatic duct stent (p = 0.005), 5.0-Fr pancreatic duct stent (p = 0.031), and male sex (p = 0.008). Pancreatic duct stent size and pancreatic duct diameter did not differ between the POPF and non-POPF groups. DISCUSSION/CONCLUSIONS: In patients with a soft pancreas, the placement of a 7.5-Fr pancreatic duct stent may reduce the incidence of POPF.