Impact of radiological and pathological splenic vein involvement in patients with resectable pancreatic body or tail cancer.

PURPOSE: Several studies have reported a negative impact on survival associated with splenic vessel involvement, especially splenic artery (SpA) involvement, in patients diagnosed with pancreatic body or tail cancer. However, there is limited research on splenic vein (SpV) involvement. Therefore, we aimed to elucidate the significance of splenic vessel involvement, especially SpV involvement, in patients with resectable pancreatic body or tail cancer. METHODS: Between January 2007 and December 2021, 116 consecutive patients underwent distal pancreatectomies for pancreatic body or tail cancer. Among them, this study specifically examined 88 patients with resectable pancreatic body or tail cancer to elucidate prognostic factors using a multivariable Cox proportional analysis. The Kaplan-Meier method evaluated the impact of SpV involvement in terms of both radiological and pathological aspects and the efficacy of neoadjuvant therapy. RESULTS: Higher pre-operative carcinoembryonic antigen levels, larger tumour size, pathological SpV invasion, and non-completion of adjuvant therapy were identified as independent poor prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Additionally, patients with radiological SpV encasement had significantly worse prognoses in terms of OS (p = 0.039) and RFS (p < 0.001). The sensitivity and specificity of multidetector-row computed tomography for detecting pathological SpV invasion were 81.0% and 61.2%, respectively. However, the prognostic impact of neoadjuvant therapy could not be determined, regardless of radiological SpV involvement. CONCLUSION: Radiological and pathological SpV involvement is a poor prognostic factor for patients with resectable pancreatic body or tail cancer. New innovative treatments and effective neoadjuvant therapy regimens are required for patients with SpV involvement.

Radiomics-based prediction of nonalcoholic fatty liver disease following pancreatoduodenectomy.

PURPOSE: Predicting nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy (PD) is challenging, which delays therapeutic intervention and makes its prevention difficult. We conducted this study to assess the potential application of preoperative computed tomography (CT) radiomics for predicting NAFLD. METHODS: The subjects of this retrospective study were 186 patients with PD from a single institution. We extracted the predictors of NAFLD after PD statistically from conventional clinical and radiomic features of the estimated remnant pancreas and whole liver region on preoperative nonenhanced CT images. Based on these predictors, we developed a machine-learning predictive model, which integrated clinical and radiomic features. A comparative model used only clinical features as predictors. RESULTS: The incidence of NAFLD after PD was 43.5%. The variables of the clinicoradiomic model included one shape feature of the pancreas, two texture features of the liver, and sex; the variables of the clinical model were age, sex, and chemoradiotherapy. The accuracy%, precision%, recall%, F1 score, and area under the curve of the two models were 75.0, 72.7, 66.7, 69.6, and 0.80; and 69.6, 68.4, 54.2, 60.5, and 0.69, respectively. CONCLUSIONS: Preoperative CT-derived radiomic features from the pancreatic and liver regions are promising for the prediction of NAFLD post-PD. Using these features enhances the predictive model, enabling earlier intervention for high-risk patients.

A comparison of pancreatojejunostomy using the modified Blumgart anastomosis with or without a four-needle three-loop suture device and continuous sutures for duct-to-mucosa anastomosis in robotic pancreaticoduodenectomy.

PURPOSE: Despite descriptions of different pancreatojejunostomy procedures using robotic pancreaticoduodenectomy (RPD), a standardized procedure has not yet been established. No prior report has described pancreatojejunostomy by RPD combined with modified Blumgart anastomosis with continuous suturing for duct-to-mucosa anastomosis. This study investigated this surgical technique and evaluated the short-term outcomes of the simplified pancreatojejunostomy procedure. METHODS: Between December 2021 and March 2024, 36 patients underwent pancreatojejunostomy using modified Blumgart anastomosis with continuous suturing for duct-to-mucosa anastomosis using RPD. Patients were divided into an early group (n = 15), without the use of the new four-needle three-loop suture device during the modified Blumgart anastomosis and a late group (n = 21) that did use this device. RESULTS: The late group had a significantly shorter pancreatojejunostomy duration (60 min vs. 49 min, p = 0.004) than the early group. Both groups showed equivalent postoperative outcomes; however, the late group exhibited a trend toward a lower rate of postoperative pancreatic fistula grade ≥ B (26.7% vs. 4.8%, p = 0.138). CONCLUSIONS: Pancreatojejunostomy using modified Blumgart anastomosis with a four-needle three-loop suture device and continuous suture for duct-to-mucosa anastomosis in patients undergoing RPD is simple and effective. This new suturing device may further reduce the incidence of postoperative pancreatic fistulas.

Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy. METHODS: Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis. RESULTS: The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001). CONCLUSIONS: Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Safety and efficacy of neoadjuvant chemotherapy based on our resectability criteria for locally advanced perihilar cholangiocarcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study evaluated the safety and efficacy of NAC for PHC. METHODS: Ninety-one PHC patients without metastases were treated at our department. Patients were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC patients without regional lymph node metastases (LNM) or those unable to tolerate NAC. The NAC regimen comprised two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. RESULTS: US and NAC were performed on 32 and 59 patients, respectively. For US, 31 patients underwent curative intent surgery (upfront-CIS). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo curative intent surgery (NAC-CIS) without impairing liver function, and spared 23/59 (39%) from undergoing resection (NAC-UR). Overall survival was better in the upfront-CIS and NAC-CIS groups than in the NAC-UR group (MST: 74 vs 57 vs 17 months, p < 0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was the highest in the LA group (27% [3/11] than in R, 30% [10/33] in BR, and 67% [10/15] in LA, p = 0.039). Multivariate analyses revealed that LA and age were independent risk factors for non-resection after NAC. CONCLUSION: was safe and contributed to improving survival in advanced PHC patients. R-PHC was responsive to NAC, but LA remains a risk factor for non-resection through NAC.

Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma.

BACKGROUND: The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). RESULTS: PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). CONCLUSION: These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.

Anterior versus posterior radical antegrade modular pancreatosplenectomy for pancreatic body and tail cancer: an inverse probability of treatment weighting with survival analysis.

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) is a standard procedure for patients with pancreatic body and tail cancer. There are two types of RAMPS: anterior and posterior, but their indications and surgical outcomes remain unclear. We compared the surgical outcomes, postoperative course, and prognosis between anterior and posterior RAMPS. METHODS: Between 2007 and 2020, 105 consecutive patients who underwent RAMPS for pancreatic body and tail cancers were divided into an anterior RAMPS group (n = 30) and a posterior RAMPS group (n = 75). To adjust for differences in preoperative characteristics and intraoperative procedures, an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. RESULTS: After IPTW adjustment, the postoperative body temperature of the posterior RAMPS group and the amount of drain discharge in the anterior RAMPS group were significantly lower, from postoperative days (PODs) 1 to 3, but there were no differences in postoperative complications, recurrence patterns, or prognosis between the two groups. Regarding the diagnostic ability of multidetector-row computed tomography (MD-CT) for direct tumor involvement of the left adrenal gland, the sensitivity and specificity were 100% and 90.0%, respectively. CONCLUSION: Pancreatic body and tail cancer without apparent preoperative direct tumor involvement of the left adrenal gland on MD-CT may be sufficient indication for anterior RAMPS.

Surgical outcomes of the Frey procedure for chronic pancreatitis: correlation between preoperative characteristics and the histological severity of pancreatic fibrosis.

PURPOSE: To evaluate the efficacy of the Frey procedure and clarify the relationship between preoperative characteristics and the histological severity of chronic pancreatitis (CP). METHODS: Thirty patients who underwent the Frey procedure for CP between January, 2002 and December, 2020, at our hospital, were enrolled in this study. The specimen cored out of the pancreatic head was assessed for CP severity. We evaluated preoperative status and surgical outcomes according to CP severity. RESULTS: Long-term pain relief was achieved in all 26 patients with sustained long-term follow-up, with complete pain relief attained in 19 (63%). Albumin levels were significantly higher 1 year postoperatively than preoperatively (p = 0.038). Histological fibrosis was assessed in the 26 patients as follows: normal (n = 4; 15%), mild (n = 8; 31%), moderate (n = 2; 8%), and severe (n = 12; 46%). These patients were divided into two groups according to the severity of fibrosis: normal/mild (n = 12) and moderate/severe (n = 14). The rates of diffuse calcification on preoperative computed tomography (CT) (71% vs. 17%, p = 0.008) and islet atrophy on insulin immunohistochemistry (100% vs. 33%, p < 0.001) were significantly higher in the moderate/severe group than in the normal/mild group. CONCLUSION: The Frey procedure can achieve good pain relief and improve nutritional status. The severity of fibrosis can be predicted based on the extent of calcification on preoperative imaging studies.

Extrapancreatic extension is a better adverse prognostic factor than tumor size in patients with localized pancreatic ductal adenocarcinoma treated with chemoradiotherapy - comparison of T category between the American Joint Committee on Cancer and Japan Pancreas Society.

BACKGROUND: T category classification for pancreatic ductal adenocarcinoma (PDAC) in the Classification of Pancreatic Cancer by the Japan Pancreas Society (JPS) is quite different from that of the American Joint Committee on Cancer (AJCC). The JPS classification focuses on extrapancreatic extension, while the AJCC focuses mainly on tumor size. This study aimed at identifying prognostic factors in PDAC patients undergoing chemoradiotherapy (CRT) by comparing the differences of T categories in these two classifications. METHODS: This retrospective study involved 344 PDAC patients who underwent CRT from 2005 to 2019 and their T-category variables were re-evaluated on computed tomography (CT) images. Disease-specific survival (DSS) was compared based on the JPS and AJCC T categories, while multivariate analysis was performed to identify prognostic factors. RESULTS: Based on the AJCC, 5-year DSS of T3 was better than those of T1 and T2 (57.1% vs. 47.7% and 37.4%). In multivariate analysis, performance status, CEA, the involvement of superior mesenteric vein and superior mesenteric artery, the JPS stage before CRT, and regimen of chemotherapy were identified as independent prognostic factors. CONCLUSIONS: In localized PDAC patients treated with chemoradiotherapy, extrapancreatic extension, as while as biological, conditional and therapeutic factors, is a better prognostic factor than tumor size.

Role of Serum Carcinoma Embryonic Antigen (CEA) Level in Localized Pancreatic Adenocarcinoma: CEA Level Before Operation is a Significant Prognostic Indicator in Patients With Locally Advanced Pancreatic Cancer Treated With Neoadjuvant Therapy Followed by Surgical Resection: A Retrospective Analysis.

OBJECTIVE: The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. SUMMARY OF BACKGROUND DATA: Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. MATERIALS AND METHOD: From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. RESULTS: In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CONCLUSIONS: CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

Resection type is a predictor of postoperative complications in laparoscopic partial liver resection.

BACKGROUND: Partial laparoscopic liver resection (LLR) is a procedure that can have varying levels of surgical difficulty depending on the tumor status and procedure. Therefore, we aimed to evaluate the surgical outcomes of partial LLR using a new resection classification system. METHODS: From January 2009 to May 2021, 156 patients underwent LLR; of them, 87 patients who underwent pure partial LLR were included in this study. They were classified according to the IWATE criteria as the low (n = 56) and intermediate (n = 31) difficulty groups and reclassified according to the resection type as the edge (ER, n = 45), bowl-shaped (BSR, n = 27), and dome-shaped resection (DSR, n = 15) groups. The following surgical outcomes were comparatively analyzed among the groups: intraoperative blood loss, the operation time, and complication rates. Preoperative risk factors for intraoperative blood transfusion and complications were evaluated. RESULTS: In the IWATE criteria-based analysis, the intermediate-difficulty group had significantly higher intraoperative blood loss (p = 0.005), operation time (p = 0.005), and Clavien-Dindo (CD) grade-based complication rates (CD grade 2 or higher, p = 0.03) than the low-difficulty group. When analyzing the resection type, the CD grade-based complication rate (p = 0.013) and surgical site infection (SSI, p = 0.005) were significantly higher and the postoperative hospitalization was significantly longer (p = 0.028) in the bowl-shaped resection (BSR) group than in the edge- (ER) and dome-shaped resection (DSR) groups. The tumor size (p = 0.011) and IWATE criteria score (p = 0.006) were independent risk factors for intraoperative blood transfusion in the multivariate analysis. The tumor depth (p = 0.011) and BSR (p = 0.002) were independent risk factors for complications of CD grade 2 or higher in the multivariate analysis. BSR was an independent risk factor for SSI in the multivariate analysis (p = 0.017). CONCLUSIONS: Resection type could predict the rate of postoperative complications, while the IWATE criteria could predict the intraoperative surgical difficulty.

The usefulness of modified splenic hilum hanging maneuver in laparoscopic splenectomy, especially for patients with huge spleen: a case-control study with propensity score matching.

BACKGROUND: Although Laparoscopic splenectomy (LS) have been proven to the standard operation for removal of spleen, the rate of conversion to open surgery is still higher than those of other laparoscopic surgeries, especially for huge spleen. In order to reduce the rate of conversion to open surgery, we had developed LS using modified splenic hilum hanging (MSHH) maneuver: the splenic pedicle was transected en bloc using a surgical stapler after hanging splenic hilum with an atraumatic penrose drain tube. METHODS: Between January 2005 and December 2019, we retrospectively assessed 94 patients who underwent LS. MSHH maneuver was performed in 37 patients (39.4%). We compared the intra- and postoperative outcomes between patients with or without MSHH maneuver. To adjust for differences in preoperative characteristics and blood examination, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 29 patients per group. Predictive factors of conversion from LS to open surgery were elucidated using the uni- and multi-variate analyses. RESULTS: After the propensity score matching, blood loss (268 ml vs. 50 ml), the rate of conversion to open surgery (27.6% vs. 0%), and postoperative hospital stays (15 days vs. 10 days) were significantly decreased in patients with MSHH maneuver, respectively. Among 94 patients, 19 patients (20.2%) underwent conversion to open surgery. In multivariate analysis, spleen volume (SV) and LS without MSHH maneuver were independent predictive factors of conversion to open surgery, respectively. Additionally, cut-off value of SV for conversion to open surgery was 802 ml (sensitivity: 0.684, specificity: 0.827, p < 0.001). CONCLUSIONS: LS using MSHH maneuver seems to be useful surgical technique to improve intraoperative outcomes and reduce the rate of conversion from LS to open surgery resulting in shorten postoperative hospital stay.

Safety and benefits of major hepatectomy with extrahepatic bile duct resection in older perihilar cholangiocarcinoma patients.

PURPOSE: To evaluate the safety and benefits of major hepatectomy with extrahepatic bile duct resection in older perihilar cholangiocarcinoma patients and to identify possible predictors of surgical mortality. METHODS: We retrospectively analyzed the data of 102 consecutive patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma in our institution between 2004 and 2021. The patients were included and divided into two groups: older patients ≥ 75 years and non-older patients < 75 years. Patient characteristics, preoperative nutritional and operative risk scores, intraoperative details, postoperative outcomes, and long-term prognosis were compared between the groups. Univariate and multivariate analyses were used to identify the predictors of 90-day mortality after major hepatectomy with extrahepatic bile duct resection. RESULTS: Significant differences were identified for some preoperative surgical risk scores, but not for nutritional scores. Older patients had a higher morbidity rate of respiratory complications (p = 0.016), but there were no significant differences in overall (p = 0.735) or disease-specific survival (p = 0.858). A high Dasari's score was identified as an independent predictive factor of 90-day mortality. CONCLUSIONS: Major hepatectomy with extrahepatic bile duct resection can be performed for optimally selected older and younger patients with perihilar cholangiocarcinoma, resulting in a good prognosis. However, indications for extended surgery should be recognized. Dasari's preoperative risk score may be a good predictor of 90-day mortality.

Risk factor analysis of postoperative pancreatic fistula after distal pancreatectomy, with a focus on pancreas-visceral fat CT value ratio and serrated pancreatic contour.

BACKGROUND: In pancreaticoduodenectomy, the pancreas-visceral fat CT value ratio and serrated pancreatic contour on preoperative CT have been revealed as risk factors for postoperative pancreatic fistulas. We aimed to evaluate whether they could also serve as risk factors for postoperative pancreatic fistulas after distal pancreatectomy. METHODS: A total of 251 patients that underwent distal pancreatectomy at our department from 2006 to 2020 were enrolled for the study. We retrospectively analyzed risk factors for postoperative pancreatic fistulas after distal pancreatectomy using various pre and intraoperative factors, including preoperative CT findings, such as pancreas-visceral fat CT value ratio and serrated pancreatic contour. RESULTS: The study population included 147 male and 104 female participants (median age, 68 years; median body mass index, 21.4 kg/m2), including 64 patients with diabetes mellitus (25.5%). Preoperative CT evaluation showed a serrated pancreatic contour in 80 patients (31.9%), a pancreatic thickness of 9.3 mm (4.0-22.0 mm), pancreatic parenchymal CT value of 41.8 HU (4.3-22.0 HU), and pancreas-visceral fat CT value ratio of - 0.41 (- 4.88 to - 0.04). Postoperative pancreatic fistulas were developed in 34.2% of the patients. Univariate analysis of risk factors for postoperative pancreatic fistulas showed that younger age (P = 0.005), high body mass index (P = 0.001), absence of diabetes mellitus (P = 0.002), high preoperative C-reactive protein level (P = 0.024), pancreatic thickness (P < 0.001), and high pancreatic parenchymal CT value (P = 0.018) were significant risk factors; however, pancreas-visceral fat CT value ratio (P = 0.337) and a serrated pancreatic contour (P = 0.122) did not serve as risk factors. Multivariate analysis showed that high body mass index (P = 0.032), absence of diabetes mellitus (P = 0.001), and pancreatic thickness (P < 0.001) were independent risk factors. CONCLUSION: The pancreas-visceral fat CT value ratio and serrated pancreatic contour evaluated using preoperative CT were not risk factors for postoperative pancreatic fistulas after distal pancreatectomy. High body mass index, absence of diabetes mellitus, and pancreatic thickness were independent risk factors, and a close-to-normal pancreas with minimal fat deposition or atrophy is thought to indicate a higher risk of postoperative pancreatic fistulas after distal pancreatectomy.

The Impact of Dabigatran Treatment on Sinusoidal Protection Against Hepatic Ischemia/Reperfusion Injury in Mice.

Thrombin is a key player in the coagulation cascade, and it is attracting much attention as a promotor of cellular injured signaling. In ischemia/reperfusion injury (IRI), which is a severe complication of liver transplantation, thrombin may also promote tissue damage. The aim of this study is to reveal whether dabigatran, a direct thrombin inhibitor, can attenuate hepatic IRI with focusing on a protection of sinusoidal endothelial cells (SECs). Both clinical patients who underwent hepatectomy and in vivo mice model of 60-minute hepatic partial-warm IRII, thrombin generation was evaluated before and after IRI. In next study, IRI mice were treated with or without dabigatran. In addition, hepatic SECs and hepatocytes pretreated with or without dabigatran were incubated in hypoxia/reoxygenation (H-R) environment in vitro. Thrombin generation evaluated by thrombin-antithrombin complex (TAT) was significantly enhanced after IRI in the clinical study and in vivo study. Thrombin exacerbated lactate dehydrogenase cytotoxicity levels in a dose-dependent manner in vitro. In an IRI model of mice, dabigatran treatment significantly improved liver histological damage, induced sinusoidal protection, and provided both antiapoptotic and anti-inflammatory effects. Furthermore, dabigatran not only enhanced endogenous thrombomodulin (TM) but also reduced excessive serum high-mobility group box-1 (HMGB-1). In H-R models of SECs, not hepatocytes, pretreatment with dabigatran markedly attenuated H-R damage, enhanced TM expression in cell lysate, and decreased extracellular HMGB-1. The supernatant of SECs pretreated with dabigatran protected hepatocytes from H-R damage and cellular death. Thrombin exacerbated hepatic IRI, and excessive extracellular HMGB-1 caused severe inflammation-induced and apoptosis-induced liver damage. In this situation, dabigatran treatment improved vascular integrity via sinusoidal protection and degraded HMGB-1 by endogenous TM enhancement on SECs, greatly ameliorating hepatic IRI.

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined. OBJECTIVE: To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC. METHODS: The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis. RESULTS: Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR. CONCLUSIONS: pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.

Association between gastric Candida colonization and surgical site infections after high-level hepatobiliary pancreatic surgeries: the results of prospective observational study.

AIM: High-level hepatobiliary pancreatic (HBP) surgeries are highly associated with surgical site infections (SSIs), in which microorganisms have a significant role. In the present study, we investigated whether gastric Candida colonization had a significant role in SSIs after high-level HBP surgeries. METHODS: Between May 2016 and February 2017, the 66 patients who underwent high-level HBP surgeries were enrolled in the present study. The gastric juice was prospectively collected through nasogastric tube after general anesthesia induction and was incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. First of all, we compared the incidence of SSIs according to the presence or absence of Candida species in gastric juice. Secondly, we evaluated the variables contributing to the development of SSIs by multivariate analysis. The protocol was approved by the medical ethics committee of Mie University Hospital (No.2987). RESULTS: Gastric Candida colonization was identified in 21 patients (group GC) and was not identified in the other 45 patients (group NGC). There were no differences in preoperative variables including compromised status, such as age, nutritional markers, complications of diabetes mellitus, and types of primary disease between the two groups. SSIs occurred in 57.1% (12/21) of group GC and in 17.8% (8/45) of group NGC, showing a significant difference (p = 0.001). Multivariate analysis revealed gastric Candida colonization as a significant risk factor of SSIs (OR 6.17, p = 0.002). CONCLUSION: Gastric Candida colonization, which is not a result of immunocompromised status, is highly associated with SSIs after high-level HBP surgeries. TRIAL REGISTRATION: Japan Primary Registries Network; UMIN-CTR ID: UMIN000040486 (retrospectively registered on 22nd May, 2020).

Proximal subtotal pancreatectomy as an alternative to total pancreatectomy for malnourished patients.

PURPOSE: To investigate whether proximal subtotal pancreatectomy (PSTP) is superior to total pancreatectomy (TP) for preserving postoperative endocrine function, and to identify the pre-operative risk factors influencing prognosis after TP and PSTP. METHODS: The subjects of this retrospective study were patients who underwent TP (n = 15) or PSTP (n = 16) between 2008 and 2018 in our hospital. First, we compared the incidence of hypoglycemia within 30 days after surgery and the total daily amount of insulin needed in the 30 days after TP vs. PSTP. Then, we compared the prognoses between the groups. RESULTS: The incidence of hypoglycemia in the 30 days after surgery was significantly lower in the PSTP group than in the TP group (n = 0 vs. n = 5; p < 0.001). The total amount of daily insulin given was also significantly lower after PSTP than after TP: (0 units vs. 18 units, p = 0.001). Lower lymphocyte counts (p = 0.014), lower cholinesterase (p = 0.021), and lower prognostic nutrition index (p = 0.021) were identified as significant risk factors for hypoglycemia in the TP group. Low cholinesterase (p = 0.015) and a low prognostic nutrition index (p = 0.048) were significantly associated with an unfavorable prognosis in the TP group, but not in the PSTP group. CONCLUSIONS: PSTP may be a feasible alternative to TP to preserve endocrine function, especially for malnourished patients.

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status.

BACKGROUND: The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. METHODS: Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. RESULTS: Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. CONCLUSION: Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection.

BACKGROUND: Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. METHODS: Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). RESULTS: In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). CONCLUSION: This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.