Effect of Risk Factor Score on Early Recurrence After Pancreatectomy for Invasive Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: This study aimed to identify the risk factors for early recurrence (ER) after pancreatic ductal adenocarcinoma (PDAC) resection to create a novel scoring system for ER and analyze their effect on the recurrence pattern. PATIENTS AND METHODS: Sixty patients with PDAC who underwent pancreatectomy were included. The predicted risk factors for ER were analyzed. A new score defining ER was created and analyzed for recurrence pattern and prognosis. RESULTS: Independent predictors included high CA 19-9 (≥147 U/ml), high lymph node ratio (LNR of ≥0.1277), and no adjuvant chemotherapy (AC). The 5-year overall survival rates with a score of 0, 1, and 2 were 55.8%, 11.0%, and 0%, respectively. In the moderate- risk score group, prognosis was improved by induction of AC within 58 days. CONCLUSION: Preoperative high CA19-9, high LNR, and no AC could be ER predictors. Induction of postoperative chemotherapy within 58 days may improve prognosis.

The Gastrohepatic Ligament Approach Using Multiple Traction Tapes in Laparoscopic Spleen-Preserving Distal Pancreatectomy with Preservation of Splenic Vessels (with Video).

BACKGROUND: The gastrohepatic ligament approach is a form of robot-assisted spleen-preserving distal pancreatectomy (SPDP).1,2 This approach does not require omentum transection, peri-splenic dissection, or stomach traction. METHODS: Considering the advantages of preserving collateral pathways around the spleen, the authors performed the gastrohepatic ligament approach in laparoscopic SPDP while preserving splenic vessels (LSPDP), with specific modifications for laparoscopic surgery. The following surgical technique was performed. First, the gastrohepatic ligament was divided extensively, and all subsequent procedures were performed through the gastrohepatic ligament route. The superior and inferior borders of the pancreas then were dissected to encircle the common hepatic and splenic arteries with vessel loops and to expose the superior mesenteric vein (SMV) and portal vein. After taping of the pancreas on the SMV, the pancreas was divided using a linear stapler. Next, the pancreas was dissected from proximal to distal with preservation of the splenic vessels. Re-taping and traction of the splenic vessels and pancreas could facilitate the dissection of the pancreas body, especially at the splenic hilum. The appropriate counter traction using traction tapes allowed efficient laparoscopic procedures. The LSPDP was performed for three patients, including one obese patient (body mass index, 36 kg/m2) and two patients with an anomalous left hepatic artery branching from the left gastric artery. RESULTS: The mean operation time was 186 min, and the intraoperative blood loss was 37 mL. CONCLUSION: The gastrohepatic ligament approach could be an option for performing LSPDP with the counter traction technique for low-grade malignant tumors.

The postoperative platelet-to-lymphocyte ratio predicts the outcome of patients undergoing pancreaticoduodenectomy for pancreatic head cancer.

PURPOSE: The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated. METHODS: We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed. RESULTS: A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028). CONCLUSIONS: The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection.

Superior mesenteric vein/portal vein contact in preoperative imaging indicates biological malignancy in anatomically resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer in contact with the superior mesenteric vein/portal vein is classified as resectable pancreatic cancer; however, the biological malignancy and treatment strategy have not been clarified. METHODS: Data from 186 patients who underwent pancreatectomy for pancreatic cancer were evaluated using a prospectively maintained database. The patients were classified as having resectable tumors without superior mesenteric vein/portal vein contact and with superior mesenteric vein/portal vein contact of ≤180°. Disease-free survival, overall survival, and prognostic factors were analyzed. RESULTS: In the univariate analysis, superior mesenteric vein/portal vein contact in resectable pancreatic cancer was a significant prognostic index for disease-free survival and overall survival. In the multivariate analysis for poor disease-free survival, the superior mesenteric vein/portal vein contact remained significant (hazard ratio = 2.13, 95% confidence interval: 1.29-3.51; p < 0.01). In the multivariate analysis, superior mesenteric vein/portal vein contact was a significant independent prognostic index for overall survival (hazard ratio = 2.17, 95% confidence interval: 1.27-3.70; p < 0.01), along with sex, tumor differentiation, nodal involvement, and adjuvant chemotherapy. Portal vein resection for superior mesenteric vein/portal vein contact did not improve the overall survival (p = 0.86). CONCLUSIONS: Superior mesenteric vein/portal vein contact in resectable pancreatic cancer was found to be an independent predictor of disease-free survival and overall survival after elective resection. Thus, pancreatic cancer in contact with the superior mesenteric vein/portal vein may be considered as borderline resectable pancreatic cancer.

Osteosarcopenia is a significant predictor of recurrence and the prognosis after resection for extrahepatic bile duct cancer.

PURPOSE: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC). METHODS: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. RESULTS: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively). CONCLUSIONS: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC.

The Impact of Fibrinogen to Prognostic Nutritional Index Rate on Prognosis of Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: The aim of the present study was to evaluate the prognostic value of the ratio of serum fibrinogen to prognostic nutritional index (PNI; Fbg/PNI) in patients undergoing resection for pancreatic ductal adenocarcinoma. METHODS: A total of 140 patients who had undergone resection for pancreatic cancer were included. Patients were divided into two groups according to a Fbg/PNI ≥8.8 or <8.8. Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis. RESULTS: Fbg/PNI was a significant prognostic indicator in univariate analysis for overall survival (OS) and disease-free survival (DFS). Fbg/PNI retained significance in multivariate analysis for OS (hazard ratio, 1.81; 95% confidence interval, 1.19-2.77; P < .01) in addition to tumor differentiation and nodal involvement. Fbg/PNI was a significant independent prognostic indicator of poor DFS on multivariate analysis (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26; P = .03). CONCLUSION: Preoperative Fbg/PNI is a novel significant independent prognostic indicator for OS and DFS following resection of pancreatic cancer with curative intent.

Preoperative Therapy for Unresectable Locally Advanced Pancreatic Cancer for ≥6 Months Improves Prognosis After Pancreatectomy.

BACKGROUND/AIM: This study aimed to identify the optimal duration of pretreatment for unresectable locally advanced (UR-LA) pancreatic cancer and analyze its effect on the prognosis. PATIENTS AND METHODS: This retrospective study included 39 patients with UR-LA pancreatic cancer after pancreatectomy. The cutoff period of preoperative therapy was determined using a receiver operating characteristic curve. We investigated the relationship between preoperative and intraoperative clinical variables and overall survival (OS) in univariate and multivariate analyses. The relationship between the preoperative therapy duration and the clinicopathological variables was investigated. OS was compared according to preoperative therapy duration and the presence or absence of adjuvant surgery. RESULTS: After pretreatment, 15 patients underwent adjuvant surgery and 24 patients continued on chemotherapy without surgery. The multivariate analysis demonstrated preoperative therapy duration ≥6 months was an independent prognostic factor [hazard ratio (HR)=0.10, p=0.04]. No significant difference in the clinicopathological variables was observed between the two groups according to preoperative therapy duration. The OS was significantly better in patients who underwent adjuvant surgery after preoperative therapy duration ≥6 months than in those after preoperative therapy duration <6 months and in those without adjuvant surgery (5-year OS rates: 80% vs. 0%; p=0.01 and 5-year OS rates: 80% vs. 0%; p=0.004, respectively). The OS was not significantly better in patients with adjuvant surgery after preoperative therapy duration <6 months than in those without adjuvant surgery (2-year OS rates: 45.7% vs. 38.1%; p=0.98). CONCLUSION: Preoperative therapy for UR-LA pancreatic cancer for ≥6 months is necessary to improve prognosis after adjuvant surgery.

Open Thoracic Drainage Followed by Proximal Splenic Artery Embolization for Massive Hydrothorax Before Living Donor Liver Transplantation.

BACKGROUND: Hepatic hydrothorax is associated with postoperative infectious complications and mortality in patients undergoing living-donor liver transplantation (LDLT). Thus, preoperative management of massive hepatic hydrothorax is essential for improving the outcomes of LDLT. This study aimed to demonstrate our successful cases and strategy for treating massive hepatic hydrothorax. METHODS: Our strategy for hepatic hydrothorax includes (a) mini-thoracotomy under general anesthesia for the drainage of hydrothorax, (b) preoperative hepatic inflow modulation by proximal splenic arterial embolization, and (c) nutritional and physical intervention to improve the general condition. RESULTS: Two patients with massive hepatic hydrothorax were treated with our strategy. Both patients had end-stage liver disease secondary to primary biliary cholangitis. Their performance status deteriorated due to massive hydrothorax. After the intervention, their performance status significantly improved. After that, LDLTs with right lobe grafts were performed. The duration of the operation was 440 and 343 minutes, with an intraoperative blood loss of 1,700 and 1,600 g, respectively. Their postoperative courses were uneventful, and they were discharged on postoperative days 16 and 14. CONCLUSION: Our pre-LDLT multimodal management strategy for massive hepatic hydrothorax, including preoperative open thoracic drainage, pre-LDLT portal inflow modulation, and nutritional intervention, improved the preoperative condition of patients undergoing LDLT, resulting in successful outcomes.

Multimodal Management for Refractory Biliary Stricture After Living Donor Liver Transplantation.

BACKGROUND: Biliary stricture is a common complication of living donor liver transplantation (LDLT). Endoscopic retrograde biliary drainage (ERBD) is the primary treatment of biliary stricture, which is sometimes refractory. This study aimed to evaluate the risk factors for biliary stricture after LDLT and present successful management for refractory biliary stricture. METHODS: Data from 26 patients who underwent LDLT were retrospectively analyzed. The relationship between the incidence of biliary strictures and clinical variables, including pre/intra/postoperative factors, was assessed. RESULTS: Univariate analysis showed that ABO incompatibility (P = .037) was a significant risk factor for biliary strictures. Case 1 was a 57-year-old woman who underwent LDLT using a left-lobe graft for primary biliary cholangitis (PBC) and developed a biliary stricture 1 month after surgery. Percutaneous transhepatic cholangiodrainage (PTCD) and embolization of the portal vein and hepatic artery were performed. Thereafter, ethanol was injected into the biliary duct, and the intervention was successfully completed. Case 2 was a 54-year-old woman who underwent LDLT using a right-lobe graft and duct-to-duct biliary reconstruction for PBC. Internal plastic stent insertion by ERBD was unsuccessful due to the significantly bending bile duct. After PTCD, the gun-site technique for the posterior branch and dual hepatic vascular embolization of the anterior branch was performed. The patient was followed up without an external fistula tube. CONCLUSION: ABO incompatibility was a risk factor for refractory biliary stricture. Appropriate procedures should be chosen based on stricture types.

The Japanese 5-5-500 Rule Predicts Prognosis of Hepatocellular Carcinoma After Hepatic Resection.

BACKGROUND: The 5-5-500 rule has been proposed to increase the candidates of liver transplantation for patients with hepatocellular carcinoma with reasonable recurrence rates. However, the clinical significance of the 5-5-500 rule in patients who underwent hepatic resection for hepatocellular carcinoma has not been fully investigated. PATIENTS AND METHODS: The study comprised 206 patients who had undergone primary hepatic resection for hepatocellular carcinoma between 2008 and 2018. We retrospectively investigated prognostic significance of the 5-5-500 rule and disease-free, as well as overall, survival and further prognostic stratification using inflammatory-based biomarkers. RESULTS: 132 patients (64%) were classified within the 5-5-500 rule, while 74 patients (36%) were classified outside the 5-5-500 rule. Among the patients outside the 5-5-500 rule, 62 patients had tumors greater than 5 cm, and 23 patients showed serum AFP levels greater than 500 ng/ml. In the multivariate analysis, being female (p<0.01), HBs-Ag positive (p<0.01), having an ICGR15 ≥15% (p=0.03), and being outside the 5-5-500 rule (p=0.01) were independent and significant predictors of disease-free survival, while being HBs-Ag positive (p=0.04), having poor tumor differentiation (p=0.03), and residing outside the 5-5-500 rule (p=0.01) were independent and negative predictors of overall survival. Elevated CRP-to-albumin ratio was associated with poor overall survival in the patients outside the 5-5-500 rule, but not in patients within the 5-5-500 rule (p=0.17). CONCLUSION: The 5-5-500 rule can be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. CRP-to-albumin ratio might be useful to stratify the outcomes in patients outside the 5-5-500 rule.

Laparoscopic cholecystectomy with the Pringle maneuver for acute cholecystitis (with video).

Horiuchi and colleagues assessed the benefits of adding the Pringle maneuver to laparoscopic cholecystectomy for acute cholecystitis. Compared with laparoscopic cholecystectomy without the Pringle maneuver, including it reduced intraoperative bleeding. Laparoscopic cholecystectomy with the Pringle maneuver is a safe and feasible option that avoids conversion to open laparotomy and prevents serious complications.

D1 Distal Pancreatectomy for Left-sided Pancreatic Ductal Adenocarcinoma Is Justifiable: A Propensity-score Matched Multicenter Study.

BACKGROUND/AIM: Evidence on the optimal extent of lymph node dissection for left-sided pancreatic ductal adenocarcinoma (PDAC) is scarce. The aim of the current study was to compare the long-term outcomes of patients who underwent D1 distal pancreatectomy (DP) with D2 DP for left-sided PDAC. PATIENTS AND METHODS: Patients undergoing DP for left-sided PDAC at the four institutions affiliated to The Jikei University were enrolled in this study. Patients were divided into D1 and D2 groups. Patients' clinical characteristics, overall survival (OS), and relapse-free survival (RFS) were compared between the two groups before and after propensity-score matched (PSM) analysis. RESULTS: Of 145 patients with left-sided PDAC, 55 patients underwent D1 DP and 90 underwent D2 DP, of whom 38 matched pairs were included in the PSM analytic cohort. In the unmatched cohort, no significant difference was found between the D1 and D2 groups for both OS (median 2.51 vs. 3.07 years; p=0.709) and RFS (median 1.47 vs. 1.27 years; p=0.565). After PSM, OS (median 2.37 vs. 3.56 years; p=0.407) and RFS (median 1.35 vs. 1.11 years; p=0.542) were not significantly different between the two groups. In a comparison of regional and systemic recurrence sites, no significant difference was observed between the two groups (p=0.500). CONCLUSION: The long-term survival of D1 DP for left-sided PDAC was not inferior to D2 DP. In an era in which the importance of multidisciplinary treatment for PDAC has been documented, unnecessary extended surgery should be avoided.

The effectiveness of adjuvant chemotherapy for Stage I pancreatic cancer based on the UICC 8th edition.

BACKGROUND: Adjuvant chemotherapy is recommended for patients with pancreatic cancer after curative resection. However, there is limited evidence regarding the efficacy and prognostic factors for adjuvant chemotherapy in patients with stage I pancreatic cancer. This study aimed to identify patients in whom chemotherapy was effective and to detect prognostic factors for stage I pancreatic cancer based on guidelines of the 8th edition of the Union for International Cancer Control (UICC). METHODS: Between 2009 and 2017, 108 patients diagnosed with stage I pancreatic cancer were enrolled in this study. They were distributed into invasion (n = 68) and non-invasion (n = 40) groups. The relationship between clinicopathological variables, including various prognostic factors, disease-free survival (DFS), and overall survival (OS), were investigated by univariate and multivariate analyses. RESULTS: Five-year survival in all patients with stage I pancreatic cancer was 38.9%. Adjuvant chemotherapy failed to improve DFS or OS in patients with stage I cancer (DFS, p = 0.26; OS, p = 0.30). In subgroup analysis, adjuvant chemotherapy significantly improved DFS (multivariate-adjusted hazard ratio (HR), 0.40; 95% confidence interval [CI], 0.21-0.78; p = 0.007) and OS (multivariate-adjusted HR, 0.32; 95% CI, 0.15-0.68; p = 0.003) in the invasion group than in non-invasion group. In contrast, in the non-invasion group, adjuvant chemotherapy failed to improve DFS and OS in univariate analysis (DFS, p = 0.992; OS, p = 0.808). CONCLUSION: For stage I pancreatic cancer, based on guidelines of the UICC 8th edition, adjuvant chemotherapy may benefit patients with extrapancreatic invasion.

Preoperative cachexia index can predict the prognosis of extrahepatic biliary tract cancer after resection.

INTRODUCTION: Cachexia is associated with poor survival of patients with bile duct cancer. The cachexia index (CXI), which comprises skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cancer cachexia. In this study, we investigated the prognostic significance of the cachexia index after surgical resection of extrahepatic biliary tract cancer. METHODS: Between January 2008 and December 2020, 124 patients underwent radical resection of extrahepatic biliary tract cancer. The skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(height)2. CXI was calculated using as: SMI × serum albumin level/neutrophil-to-lymphocyte ratio. We performed univariate and multivariate analyses of the relationships between clinicopathological variables and disease-free and overall survival. RESULTS: The CXI-low group included 57 patients. CXI-low was associated with poor disease-free (p < 0.01) and overall survival (p < 0.01) after curative resection. Preoperative bile duct drainage (p = 0.01), poor tumor differentiation (p = 0.04), advanced Tumor-Nodes-Metastasis (TNM) stage (II or III) (p < 0.01), and CXI-low (p = 0.03) were independent and significant predictors of disease-free survival. Age > 70 years (p = 0.03), preoperative bile duct drainage (p < 0.01), poor tumor differentiation (p = 0.01), advanced TNM stage (II or III) (p = 0.03), and CXI-low (p = 0.04) were independent and significant predictors of overall survival. CONCLUSION: In extrahepatic biliary tract cancer, preoperative CXI-low was an independent and significant risk factor for recurrence and poor prognosis, suggesting that cancer cachexia may progress to tumor development and recurrence.

Inhibition of lysosomal acid ß-glucosidase induces cell apoptosis via impairing mitochondrial clearance in pancreatic cancer.

Sphingolipid metabolism plays an important role in the formation of cellular membranes and is associated with malignant potential and chemosensitivity of cancer cells. Sphingolipid degradation depends on multiple lysosomal glucosidases. We focused on acid ß-glucosidase (GBA), a lysosomal enzyme the deficiency of which is related to mitochondrial dysfunction. We analyzed the function of GBA in pancreatic ductal adenocarcinoma (PDAC). Human PDAC cell lines (PANC-1, BxPC-3 and AsPC-1) were examined under conditions of GBA knockdown via the short interfering RNA (siRNA) method. We assessed the morphological changes, GBA enzyme activity, GBA protein expression, cell viability, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) and mitophagy flux of PDAC cells. The GBA protein level and enzyme activity differed among cell lines. GBA knockdown suppressed cell proliferation and induced apoptosis, especially in PANC-1 and BxPC-3 cells, with low GBA enzyme activity. GBA knockdown also decreased the MMP and impaired mitochondrial clearance. This impaired mitochondrial clearance further induced dysfunctional mitochondria accumulation and ROS generation in PDAC cells, inducing apoptosis. The antiproliferative effects of the combination of GBA suppression and gemcitabine were higher than those of gemcitabine alone. These results showed that GBA suppression exerts a significant antitumor effect and may have therapeutic potential in the clinical treatment of PDAC.

Phase II trial of nafamostat mesilate/gemcitabin/S-1 for unresectable pancreatic cancer.

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 (BSA<1.25 m2), 100 mg/day (1.25 ≤ BSA<1.5 m2), or 120 mg/day (BSA ≥1.5 m2)] on days 1-14 or, days 1-7 and 15-21. This regimen was repeated at 28-day intervals. RESULTS: 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.

The impact of S-1 for the patient with lymph nodal metastasis biliary tract cancer as adjuvant chemotherapy: a multicenter database analysis.

INTRODUCTION: Although adjuvant chemotherapy is expected to improve the prognosis for patients with biliary tract cancer after curative resection, there is limited evidence regarding the efficacy and prognostic factors of adjuvant chemotherapy. We investigated the effective subgroups for whom adjuvant chemotherapy with S-1 in biliary tract cancer patients. METHODS: 413 patients who underwent curative resection for biliary tract cancer at our four affiliated hospitals between 2009 and 2019 were included in this study. The association of adjuvant chemotherapy with long-term outcomes in overall and patient subgroups were investigated by univariate and multivariate analyses. RESULTS: Among overall patients, adjuvant chemotherapy with S-1 did not improve disease free survival (p = 0.29) and overall survival (p = 0.83). In the subgroup analysis, adjuvant chemotherapy with S-1 improved both disease-free and overall survival in patients with lymph node metastasis, advanced Stage (III and IV), and microscopic residual tumor. In 135 patients with lymph node metastasis, adjuvant chemotherapy with S-1 was given in 67 patients (50%). In the patients with lymph node metastasis, preoperative bile duct drainage (p = 0.01) and adjuvant chemotherapy (p = 0.04) were independent and significant predictors of disease-free survival, while preoperative bile duct drainage (p = 0.03), tumor differentiation (p = 0.03), and adjuvant chemotherapy (p = 0.03) were independent and significant predictors of overall survival. CONCLUSION: After resection of biliary tract cancer, adjuvant chemotherapy with S-1 appears to benefit those who had lymph node metastasis.

Effects of an enteral nutrient-rich therapy with omega-3 fatty acids in patients with unresectable or recurrent biliary tract cancer or pancreatic cancer during chemotherapy: a case-control study.

To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric nutritional supplements containing omega-3 fatty acids (Racol®) was administered to aforementioned patients with cancers during chemotherapy. The skeletal muscle mass and blood test data were obtained pre-administration and 28 and 56 days after. Patients with pancreatic cancer were administered the digestive enzyme supplement pancrelipase (LipaCreon®) 28 days after the start of Racol® administration. The number of chemotherapies skipped due to neutropenia was recorded for 2 months before and after enteral nutrient initiation. In all 39 patients, the skeletal muscle mass increased on day 56 versus baseline (median 17.3 kg vs. 14.8 kg, p < 0.01), number of chemotherapies skipped decreased (mean: 0.65 times/month vs. 1.3 times/month, p = 0.03), and retinol-binding protein (mean: 2.56 mg/dL vs. 2.42 mg/dL, p = 0.05) increased. Patients with pancreatic cancer showed increased blood eicosapentaenoic acid concentration on day 56 versus baseline (median: 48.1 µg/mL vs. 37.0 µg/mL, p = 0.04) and increased skeletal muscle mass (median 16.8 kg vs. 14.4 kg, p = 0.006). Baseline median neutrophil count increased significantly from 2200/µL at baseline to 2500/µL (p = 0.04). Patients with biliary tract cancer during chemotherapy also exhibited increased skeletal muscle mass following omega-3 supplementation (median 17.3 kg vs. 15.8 kg, p = 0.01). In patients undergoing chemotherapy for unresectable or post-recurrence pancreatic and biliary tract cancers, high-omega-3 fatty acid nutrition therapy use improved skeletal muscle maintenance and chemotherapy dosing intensity.

Conversion surgery for undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a case report.

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.

Strategies and tactics to perform safe pancreaticoduodenectomy for 94-year-old patient: report of a case.

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.