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Abstract Background Despite improvement of postoperative management, pancreatoduodenectomy still has a high rate of major complications. Therefore, careful assessment is critically important when we consider high risk surgery for extremely elderly patients. Case presentation A 94-year-old man, who suffered dark urine, epigastric pain, and loss of appetite, was diagnosed as bile duct cancer and underwent endoscopic retrograde biliary drainage. He has past history of hypertension and paroxysmal atrial fibrillation. Computed tomography (CT) showed a nodule in the lower bile duct, which was slowly enhanced by dynamic CT. The patient was evaluated whether he overcomes pancreatoduodenectomy by cardiac ultrasonography, brain magnetic resonance angiography, nutritional evaluation (rapid turnover proteins), and CT-based general assessment, including sarcopenia and osteopenia. The patient was independent in activities of daily living and has enough ejection fraction of 65%, and examinations revealed no impairment of cognitive function, sarcopenia, and osteopenia. With a diagnosis of bile duct cancer with no distant metastasis, the patient underwent subtotal stomach-preserving pancreatoduodenectomy with lymph node dissection. Operation time was 299 min and estimated blood loss was 100 ml. Pathological examination revealed papillary adenocarcinoma of the bile duct (pT3N1M0 Stage IIIB). Enteral nutrition was given through jejunostomy and then the patient started oral intake after an evaluation of swallowing function. Postoperative course was uneventful and all drains including pancreatic duct stent, biliary stent, and jejunostomy were removed by 3 weeks after operation. The levels of rapid turnover proteins dropped at postoperative day 7, but recovered at 1 month after operation via appropriate nutrition and rehabilitation. He remains well with no evidence of tumor recurrence as of 1 year after resection. Conclusions We herein report successfully treated cases of bile duct cancer in 94-year-old patient by pancreatoduodenectomy with careful evaluation of osteopenia, sarcopenia and nutrition.

Abstract Background Undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) is a rare subtype of pancreatic cancer (PC), and its clinicopathological characteristics are still unclear. Herein, we report a case of initially unresectable UCOGC that was successfully resected after FOLFIRINOX therapy. Case presentation A 63-year-old man was referred to us for evaluation of a pancreatic mass detected by computed tomography (CT) during a medical checkup. Computed tomography showed a 7.5-cm tumor located in the pancreatic head and body, which involved the common hepatic artery (CHA), gastroduodenal artery (GDA), and main portal vein (PV) with tumor thrombus. UCOGC was suspected by endoscopic ultrasonography-guided fine needle aspiration, and the patient was diagnosed with unresectable locally advanced pancreatic cancer. After ten cycles of FOLFIRINOX, the tumor size decreased to 3 cm and the tumor thrombus in the main portal trunk had disappeared in the follow-up CT scan. However, the patient experienced severe adverse drug reactions, including neutropenia and liver dysfunction. Therefore, we performed pancreatoduodenectomy with portal vein resection. The pathological diagnosis was UCOGC with a negative tumor margin. He was treated with FOLFIRINOX, and remains recurrence-free for 6 months after surgery. Conclusions We experienced a case undergoing conversion surgery for unresectable UCOGC, which resulted in R0 resection. FOLFIRINOX could be a possible regimen to achieve conversion surgery for UCOGC.

Abstract Background The administration of direct-acting antiviral agents in patients with liver cirrhosis and hepatitis C has been shown to improve liver function and long-term prognosis after sustained virological response (SVR) is achieved. However, in patients with portal hypertension (PH) at the time of SVR, PH may persist despite improvement in liver function. Case presentation An 82-year-old woman with liver cirrhosis due to hepatitis C was treated with direct-acting antiviral agents and achieved SVR. During follow-up, computed tomography revealed a low-density tumor in the left lateral region of the liver with dilation of the left intrahepatic bile duct. Considering the patient’s advanced age and PH persistence with a mild decrease in liver reserve function after SVR, preoperative percutaneous transhepatic portal embolization (PTPE) and partial splenic embolization (PSE) were performed concomitantly. Laparoscopic left hemihepatectomy was performed 8 days after the PTPE and PSE. The patient was discharged 8 days after surgery without any postoperative complications. Conclusions Laparoscopic left hemihepatectomy after preoperative management of PH was performed safely in a patient after the elimination of hepatitis C.

Abstract Aim The prognostic impact of postoperative systemic inflammatory response using an intra/post‐operative prognostic scoring system in patients with colorectal liver metastases (CRLM) after hepatic resection had never been investigated previously. Methods In total, 149 patients who underwent hepatic resection for CRLM were analyzed retrospectively. Intra/post‐operative prognostic scoring was performed using the postoperative modified Glasgow Prognostic Score (mGPS) at the first visit, after discharge, or a month after surgery during hospitalization. We investigated the association between clinicopathologic variables and disease‐free survival or overall survival by univariate and multivariate analyses. Results The median evaluation period of postoperative mGPS was 30 (26‐36) days after hepatectomy. Seventy‐one patients (48%) were classified as postoperative day 30 mGPS 1 or 2. In multivariate analysis, an extrahepatic lesion (P = .02), multiple tumors (P = .05), and postoperative day 30 mGPS 1 or 2 (P

Abstract Background Pancreatic cancer is one of the most aggressive digestive cancers. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not been confirmed in hepato‐pancreato‐biliary cancer. The aim of this study was to evaluate the prognostic value of TM expression in resected pancreatic ductal adenocarcinoma. Methods The data of patients who underwent pancreatic resection for pancreatic invasive ductal adenocarcinoma were obtained from a prospectively maintained database. A total of 131 patients were included. Paraffin sections of tumor tissues were stained immunohistochemically using TM antibody. The patients were divided into two groups: the TM‐positive or TM‐negative group. Results The specimens were TM‐positive in 72 cases. TM expression was a significant factor of favorable prognosis in univariate analysis for disease‐free (DFS) and overall survival (OS). The median OS in the TM‐positive patients was 32.9 mo, which was better than the 20.0 mo in TM‐negative patients (P =.006). TM positivity retained its significance on multivariate analysis for DFS (hazard ratio [HR] 0.651, 95% confidence interval [CI] 0.433–0.979, P =.039) and OS (HR 0.569, 95% CI 0.376–0.862, P =.008). Conclusions The tumor expression of TM is a favorable factor for OS in resected pancreatic invasive ductal adenocarcinoma.

Abstract Aim We investigated the prognostic impact of osteosarcopenia, which is the combination of osteopenia and sarcopenia, in patients with colorectal liver metastases (CRLM) after hepatic resection. Methods One hundred and eighteen patients were analyzed retrospectively. Osteopenia was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated with psoas muscle areas at the third lumbar vertebra. Osteosarcopenia was defined as the concomitant occurrence of osteopenia and sarcopenia. Results Osteosarcopenia was identified in 38 (32%) of the patients. In univariate analysis, the overall survival was significantly worse in patients with lymph node metastases (P = .01), extrahepatic lesion (P = .01), sarcopenia (P = .02), osteosarcopenia (P

Abstract Background Cholesterol crystal embolism (CCE) following transcatheter arterial chemoembolization (TACE) is rare. Case presentation A 71-year-old man underwent TACE for recurrence of hepatocellular carcinoma (HCC). On postoperative day (POD) 5, he developed abdominal pain and fever. Computed tomography revealed intraperitoneal free air. The patient was diagnosed with gastrointestinal perforation with peritonitis, for which partial intestinal resection and covering ileostomy were performed. Histological examination revealed perforation of the small intestine caused by CCE. The patient made a satisfactory recovery and was discharged on POD 30. The patient showed no recurrence of cholesterol crystal embolism or HCC for 2 years after surgery. Conclusion We reported a successfully treated case of ischemic small bowel perforation due to cholesterol crystal embolism following transcatheter arterial chemoembolization for recurrent HCC.

Abstract Aim This study sought to evaluate the incidence, risk factors, and clinical outcomes of portal vein thrombosis after hepatectomy. Furthermore, we proposed a novel classification and treatment strategy for portal vein thrombosis after hepatectomy. Methods We retrospectively analyzed 398 patients who underwent hepatectomy and enhanced computed tomography imaging within 14 days after surgery in our hospital from 2009 to 2019. Portal vein thrombosis was classified into three categories according to the location of the thrombus – main, hilar, and peripheral – with main portal vein thrombosis further subclassified into three grades. Each patient's treatment strategy was determined based on their portal vein thrombosis classification and grading. From 2015, enhanced computed tomography imaging was performed routinely on patients who underwent anatomical hepatectomy on postoperative day 7. Results Portal vein thrombosis was diagnosed in 57 patients (14.3%) during the study period. Multivariate analysis revealed that a Pringle maneuver time of 75 minutes or longer was a significant predictor of portal vein thrombosis (P = .012). In total, 52 patients (91%) with portal vein thrombosis recovered by surgery, anticoagulant therapy, or without specific treatment. There was no instance of mortality recorded. Conclusions Patients who undergo hepatectomy are at high risk for portal vein thrombosis, especially when the Pringle maneuver time is long. The proposed classification and treatment strategy may be useful for clinical management of patients with portal vein thrombosis after hepatectomy.

Purpose To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients. Materials and methods The study was conducted as a single-arm, single center, institutional review board-approved phase II trial. Patients received nafamosntat mesilate (4.8 mg/kg continuous transregional arterial infusion) with gemcitabine (1000 mg/m2 transvenous) on days 1 and15, and with oral S-1 [(80 mg/day (BSAResults Forty-seven evaluable patients (Male/Female: 31/16, Age (median): 66 (range 35–78) yrs, Stage III/IV 10/37.) were candidates in this study. Two patients in stage III (20%) could undergo conversion surgery. Twenty-four patients (51%) underwent subsequent treatment (1st line/ 2nd line / 4th line, 13/ 10/ 1, FOLFIRINOX: 12, GEM/nab-PTX: 18, TAS-118: 3, chemoradiation with S-1: 2, GEM/Erlotinib: 1, nal-IRI: 1, surgery: 2). Median PFS and OS were 9.7 (95% CI, 8.9–14.7 mo) and 14.2 months (99% CI, 13.3–23.9 mo), respectively. Median PFS in stage IV patients was 9.2 months (95% CI, 8.4–12.0 mo). Median OS in patients without subsequent treatment was 10.8 months (95% CI, 9.1–13.8 mo). Median OS in patients with subsequent treatment was 19.3 months (95% CI, 18.9–31.9 mo). Grade 4 treatment-related hematological toxicities were encountered in 7 patients. Two patients developed grade 3 allergic reaction after 6 cycles or later. No febrile neutropenia has been observed. Conclusion NAM/GEM/S-1 therapy is safe and could be promising option for unresectable pancreatic cancer, especially for stage IV cancer.

Abstract Background Calcifying fibrous tumor (CFT) is a rare benign soft tissue lesion. Case presentation A 30-year-old woman was admitted to our hospital with complaints of epigastralgia. A 15-mm submucosal tumor was identified in the greater curvature of the superior body of the stomach by upper gastrointestinal endoscopy. Endoscopic ultrasonography revealed a hypoechoic lesion with an acoustic shadow consistent with calcification. Computed tomography showed a gastric tumor with calcification. A gastrointestinal stromal tumor was diagnosed, and gastric wedge resection was performed by laparoscopy and endoscopy cooperative surgery. On pathological examination, the tumor was identified to be a CFT. Postoperative serum IgG4 levels were 26.0 mg/dl, which supported the diagnosis of probable immunoglobulin G (IgG) 4-related disease, according to the comprehensive diagnostic criteria of IgG4-related disease. The patient was discharged on postoperative day 7 and remains well with no evidence of tumor recurrence for 2 years after resection. Conclusion We herein reported a patient with a gastric CFT suspected to be complicated with immunoglobulin G4-related disease that was successfully treated by laparoscopy and endoscopy cooperative surgery.

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 μg/mL and 40 μg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.

Although the inhibition of acid ceramidase (AC) is known to induce antitumor effects in various cancers, there are few reports in pancreatic cancer, and the underlying mechanisms remain unclear. Moreover, there is currently no safe administration method of AC inhibitor. Here the effects of gene therapy using siRNA and shRNA for AC inhibition with its mechanisms for pancreatic cancer were investigated. The inhibition of AC by siRNA and shRNA using an adeno-associated virus 8 (AAV8) vector had antiproliferative effects by inducing apoptosis in pancreatic cancer cells and xenograft mouse model. Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. These results elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background/Aim: Useful prophylaxes of chyle leak (CL) after pancreatic surgery have not been established. The aim of the study was to identify an early clinical predictor for CL. Patients and Methods: Fifty-five patients who underwent subtotal stomach preserved pancreaticoduodenectomy (SSPPD) were included. Clinical factors associated with postoperative CL were evaluated. Results: Eleven patients (20%) developed a CL after SSPPD. Shorter operative time, absent pancreatic fistula, and triglyceride output volume at postoperative day (POD) two were independent risk factors for CL. The receiver operating characteristics curve of the daily triglyceride output volume at POD two indicated a cutoff point of 177 mg (AUC=0.782; p=0.004; 95% CI=0.639- 0.925). CL was significantly associated with prolonged postoperative hospital stay in patients who did not develop a pancreatic fistula (p=0.003). Conclusion: Daily triglyceride output volume of >177 mg at POD two may be a predictor of CL following pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]