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Purpose: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. Methods: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. Results: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. Conclusion: Early-onset HVOD developing within 14 days after LT has a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of major postoperative complications (POCs) for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. We sought to analyze the relationship between POCs and outcomes relative to lymph node metastases (LNM) and tumor burden score (TBS). Methods: Patients who underwent resection of ICC between 1990–2020 were included from an international database. POCs were defined according to Clavien-Dindo classification ≥ 3. The prognostic impact of POCs was estimated relative to TBS categories (i.e., high and low) and lymph node status (i.e., N0 or N1). Results: Among 553 patients who underwent curative-intent resection for ICC, 128 (23.1%) individuals experienced POCs. Low TBS/N0 patients who experienced POCs presented with a higher risk of recurrence and death (3-year cumulative recurrence rate; POCs: 74.8% vs. no POCs: 43.5%, p = 0.006; 5-year overall survival [OS], POCs 37.8% vs. no POCs 65.8%, p = 0.003), while POCs were not associated with worse outcomes among high TBS and/or N1 patients. The Cox regression analysis confirmed that POCs were significant predictors of poor outcomes in low TBS/N0 patients (OS, hazard ratio [HR] 2.91, 95%CI 1.45–5.82, p = 0.003; recurrence free survival [RFS], HR 2.42, 95%CI 1.28–4.56, p = 0.007). Among low TBS/N0 patients, POCs were associated with early recurrence (within 2 years) (Odds ratio [OR] 2.79 95%CI 1.13–6.93, p = 0.03) and extrahepatic recurrence (OR 3.13, 95%CI 1.14–8.54, p = 0.03), in contrast to patients with high TBS and/or nodal disease. Conclusions: POCs were independent, negative prognostic determinants for both OS and RFS among low TBS/N0 patients. Perioperative strategies that minimize the risk of POCs are critical to improving prognosis, especially among patients harboring favorable clinicopathologic features. [ABSTRACT FROM AUTHOR]

Purpose: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. Methods: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. Results: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3–49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 − 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. Conclusions: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area. Methods: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011–2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus. Results: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830). Conclusions: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: The present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC). Methods: Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort. Results: The DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in the CDK14 gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively. Conclusion: These findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatocellular carcinoma (HCC) may have a heterogeneous presentation, as well as different long-term outcomes following surgical resection. We sought to use machine learning to cluster patients into different prognostic groups based on preoperative characteristics. Methods: Patients who underwent curative-intent liver resection for HCC between 2000 and 2020 were identified from a large international multi-institutional database. A hierarchical cluster analysis was performed based on preoperative factors to characterize patterns of presentation and define disease-free survival (DFS). Results: Among 966 with HCC, 3 distinct clusters were identified: Cluster 1 (n = 160, 16.5%), Cluster 2 (n = 537, 55.6%) and Cluster 3 (n = 269, 27.8%). Cluster 1 (n = 160, 16.5%) consisted of female patients (n = 160, 100%), low inflammation-based scores, intermediate tumor burden score (TBS) (median: 4.71) and high alpha-fetoprotein (AFP) levels (median 41.3 ng/mL); Cluster 2 consisted of male individuals (n = 537, 100%), mainly with a history of HBV infection (n = 429, 79.9%), low inflammation-based scores, intermediate AFP levels (median 26.0 ng/mL) and lower TBS (median 4.49); Cluster 3 was comprised of older patients (median age 68 years) predominantly male (n = 248, 92.2%) who had low incidence of HBV/HCV infection (7.1% and 8.2%, respectively), intermediate AFP levels (median 16.8 ng/mL), high inflammation-based scores and high TBS (median 6.58). Median DFS worsened incrementally among the three different clusters with Cluster 3 having the lowest DFS (Cluster 1: median not reached; Cluster 2: 34 months, 95% CI 23.0–48.0, Cluster 3: 19 months, 95% CI 15.0–29.0, p < 0.05). Conclusion: Cluster analysis classified HCC patients into three distinct prognostic groups. Cluster assignment predicted DFS following resection of HCC with the female cluster having the most favorable prognosis following HCC resection. [ABSTRACT FROM AUTHOR]

Background: We sought to define surgical outcomes among elderly patients with Alzheimer's disease and related dementias (ADRD) following major thoracic and gastrointestinal surgery. Methods: A retrospective cohort study was used to identify patients who underwent coronary artery bypass grafting (CABG), abdominal aortic aneurysm (AAA) repair, pneumonectomy, pancreatectomy, and colectomy. Individuals were identified from the Medicare Standard Analytic Files and multivariable regression was utilized to assess the association of ADRD with textbook outcome (TO), expenditures, and discharge disposition. Results: Among 1,175,010 Medicare beneficiaries, 19,406 (1.7%) patients had a preoperative diagnosis of ADRD (CABG: n = 1,643, 8.5%; AAA repair: n = 5,926, 30.5%; pneumonectomy: n = 590, 3.0%; pancreatectomy: n = 181, 0.9%; and colectomy: n = 11,066, 57.0%). After propensity score matching, patients with ADRD were less likely to achieve a TO (ADRD: 31.2% vs. no ADRD: 40.1%) or be discharged to home (ADRD: 26.7% vs. no ADRD: 46.2%) versus patients who did not have ADRD (both p < 0.001). Median index surgery expenditures were higher among patients with ADRD (ADRD: $28,815 [IQR $14,333–$39,273] vs. no ADRD: $27,101 [IQR $13,433–$38,578]; p < 0.001) (p < 0.001). On multivariable analysis, patients with ADRD had higher odds of postoperative complications (OR 1.32, 95% CI 1.25–1.40), extended length‐of‐stay (OR 1.26, 95% CI 1.21–1.32), 90‐day readmission (OR 1.37, 95% CI 1.31–1.43), and 90‐day mortality (OR 1.76, 95% CI 1.66–1.86) (all p < 0.001). Conclusion: Preoperative diagnosis of ADRD was an independent risk factor for poor postoperative outcomes, discharge to non‐home settings, as well as higher healthcare expenditures. These data should serve to inform discussions and decision‐making about surgery among the growing number of older patients with cognitive deficits. [ABSTRACT FROM AUTHOR]

Background. Acute necrotizing esophagitis (ANE) is a rarely described entity that is thought to be a cause of upper gastrointestinal (UGI) bleeding, The present study examined the incidence of ANE among patients with UGI bleeding, as well as the clinical features of ANE, and the coexisting illnesses and medication histories of ANE patients. Methods. A retrospective analysis of clinical and endoscopic findings and the clinical course in 16 patients with ANE was carried out over a 3-year period. Results. We observed 16 patients (6%) of ANE in 239 patients with UGI bleeding during the 3-year period. The average age of the patients was 62.5 years. The lesions predominantly affected the lower third of the esophagus, and hiatal hernia was the most common (63%) coexisting endoscopic finding. All patients had coexisting disease. Fifty percent of patients with ANE (eight patients) had taken nonsteroidal anti-inflammatory drugs (NSAIDs). ANE also occurred in four patients with diabetic ketoacidosis. Supportive therapy, including parenteral nutrition and administration of a proton pump inhibitor, was effective. Conclusions. ANE is more common than has been previously reported, and it should be included in the differential diagnosis of UGI bleeding. ANE could be characterized as an ‘acute esophageal mucosal lesion,’ particularly in aged patients with hiatal hernia and among those who consume NSAIDs. [ABSTRACT FROM AUTHOR]

Background. Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro. Methods. Tumor sections from 79 patients who underwent endoscopic mucosal resection for early intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on COX-2 expression and activity in human gastric cell lines. Results. Among the 79 early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions) and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2 immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in early gastric cancer located in the gastric pylorus, compared with that in the other locations. In human gastric cell lines, bile acids induced COX-2 expression, mediated by the ERK 1/2 mitogenactivated protein kinase pathway. Conclusions. COX-2 expression is elevated in early gastric cancer of the gastric pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in human gastric cell lines, suggesting a role of bile reflux in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Sunitinib is approved for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable, locally advanced or metastatic disease. Safety and efficacy data in Japanese patients are limited. We report outcomes from a post-marketing surveillance study of sunitinib treatment in Japanese patients.Methods: Sunitinib 37.5 mg once daily was orally administered in Japanese patients aged ≥ 15 years with pNETs. The primary endpoints included adverse events (AEs) occurring during the observation period of 168 days and objective response rate (ORR).Results: Sunitinib was administered in 62 patients with pNETs. The median duration of treatment was 165 days. At 168 days from the start of treatment, 31 patients were still receiving sunitinib treatment and treatment continuation rate was 50.0%. Of the 31 patients who discontinued treatment, 18 (58.1%) discontinued because of AEs and 16 (51.6%) patients discontinued due to insufficient clinical effect. Of the 18 patients who discontinued due to AEs, 10 did so within 42 days of treatment initiation. The most common all-grade AEs were platelet count decreased (33.9%), diarrhea (29.0%), neutrophil count decreased (27.4%), hypertension (24.2%), and palmar-plantar erythrodysesthesia syndrome (24.2%). In the 51 patients eligible for the efficacy analysis, ORR was 13.7% (95% confidence interval, 5.7-26.3) and clinical benefit rate was 70.6%.Conclusions: There were no new safety concerns in real-world use of sunitinib in Japanese patients with pNETs. The short treatment duration likely led to low tumor response. Appropriate AEs management through dose interruption/reduction is essential for sunitinib treatment success in this patient population. [ABSTRACT FROM AUTHOR]

Background:Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery.Methods:Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA.Results:Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival.Conclusions:Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response. [ABSTRACT FROM AUTHOR]

Abstract: Gastrointestinal stromal tumor (GIST) in the distal third of the rectum was detected in a 57-year-old man who underwent an abdominoperineal resection of the rectum. Because the tumor expressed CD34 and c-kit gene product, but did not express smooth muscle actin or S-100 protein, it was diagnosed as an uncommitted type of GIST. Moreover, a specific mutation in the sequence coding the juxtamembrane domain in exon 11 of the c-kit proto-oncogene was revealed by a polymerase chain reaction-single-strand conformation polymorphism method. One year after resection, the patient developed multiple liver metastases. It is suggested that a specific mutation in exon 11 of the c-kit proto-oncogene may have played an essential role in the development of the liver metastases. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery.Methods: Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA.Results: Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival.Conclusions: Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response. [ABSTRACT FROM AUTHOR]