Clinical significance of postoperative complications after pancreatic surgery in time-to-complication and length of postoperative hospital stay: a retrospective study.

PURPOSE: We retrospectively analyzed pancreatectomy patients and examined the occurrence rate and timing of postoperative complications (time-to-complication; TTC) and their impact on the length of postoperative hospital stay (POHS) to clarify their characteristics, provide appropriate postoperative management, and improve short-term outcomes in the future. METHODS: A total of 227 patients, composed of 118 pancreaticoduodenectomy (PD) and 109 distal pancreatectomy (DP) cases, were analyzed. We examined the frequency of occurrence, TTC, and POHS of each type of postoperative complication, and these were analyzed for each surgical procedure. Complications of the Clavien-Dindo (CD) classification Grade II or higher were considered clinically significant. RESULTS: Clinically significant complications were observed in 70.3% and 36.7% of the patients with PD and DP, respectively. Complications occurred at a median of 10 days in patients with PD and 6 days in patients with DP. Postoperative pancreatic fistula (POPF) occurred approximately 7 days postoperatively in both groups. For the POHS, in cases without significant postoperative complications (CD ≤ I), it was approximately 22 days for PD and 11 days for DP. In contrast, when any complications occurred, POHS increased to 30 days for PD and 19 days for DP (each with additional 8 days), respectively. In particular, POPF prolonged the hospital stay by approximately 11 days for both procedures. CONCLUSION: Each postoperative complication after pancreatectomy has its own characteristics in terms of the frequency of occurrence, TTC, and impact on POHS. A correct understanding of these factors will enable timely therapeutic intervention and improve short-term outcomes after pancreatectomy.

Changes in and clinical utility of maximum phonation time and repetitive saliva swallowing test scores after esophagectomy.

BACKGROUND: Postoperative pneumonia in patients with esophageal cancer occurs due to swallowing dysfunction and aspiration. Recently, maximum phonation time (MPT) assessment and repetitive saliva swallowing test (RSST) have been focused on as swallowing function assessment methods that can identify patients as high risk for pneumonia. We aimed to evaluate the clinical utility of MPT assessment and RSST in patients undergoing oncological esophagectomy. METHODS: In total, 47 consecutive patients who underwent esophagectomy for esophageal cancer between August 2020 and July 2023 were eligible. The perioperative changes in MPTs and RSST scores were examined. In addition, univariate and multivariate analyses were performed to identify the predictive factors of postoperative pneumonia. RESULTS: The median MPTs before surgery and on postoperative days (PODs) 3, 6, and 10 were 18.4, 7.2, 10.6, and 12.4 s, respectively; postoperative MPTs were significantly lower than preoperative MPT. In addition, the MPT of POD 6 was significantly longer than that of POD 3 (P < 0.05). Meanwhile, there were no significant changes in perioperative RSST scores. Overall, 8 of 47 patients (17.0%) developed pneumonia postoperatively. A short MPT on POD 6 was one of the independent predictive factors for the incidence of postoperative pneumonia (odds ratio: 12.6, 95% confidence interval: 1.29-123, P = 0.03) in the multivariate analysis. CONCLUSIONS: The MPT significantly decreased after esophagectomy. However, the RSST score did not. The MPT on POD6 can be a predictor of postoperative pneumonia.

Re-consideration of Lymph Node Metastasis in Pancreatic Cancer Patients Following Radical Resection: A Retrospective Study.

BACKGROUND/AIM: Perioperative chemotherapy has become more common in patients with pancreatic cancer (PC), and the significance of lymph node (LN) metastasis and the role of surgical resection in PC have gradually evolved. In the present study, we reconsidered the significance of LN metastasis for patients with PC. PATIENTS AND METHODS: We analyzed 142 PC patients who underwent radical resection at our hospital between September 2012 and December 2021. Patients were divided into three groups based on the performance of preoperative chemotherapy, as follows: up-front surgery (US, n=109), neoadjuvant chemotherapy (NAC, n=22), and conversion surgery (CS, n=11). The characteristics of patients with LN metastasis in the US group were clarified, and a prognostic analysis was performed. The prognostic impact of LN metastasis in the NAC/CS group was examined and compared to that in the US group. RESULTS: Multivariate analysis revealed that high CA19-9 levels, large tumor size, and positive lymphatic invasion were significantly associated with LN metastasis. LN metastasis and portal vein invasion were independent poor prognostic factors in multivariate analysis. Patients without LN metastasis in the NAC group tended to have a better prognosis than those in the US group; however, the prognosis of patients with LN metastasis was similar between the two groups. In the CS and US groups, the prognosis was comparable for patients with and without LN metastasis. CONCLUSION: LN metastasis is a notably poor prognostic factor for PC patients, even after NAC, and more aggressive perioperative treatments may be considered for these patients.

A Case of Pathologically Complete Response After Nivolumab Combined with Chemotherapy in a Gastric Cancer Patient with Virchow's Lymph Node Metastasis.

Gastric cancer with Virchow's lymph node metastasis (LNM) is not indicated for initial curative surgery. Although there have been some case reports of curative resections after pre-operative treatment, including immune checkpoint inhibitors (ICIs), there is no consensus regarding the optimal timing of surgery. We describe a rare case of initially unresectable gastric cancer treated preoperatively with nivolumab combined chemotherapy, which achieved a pathologically complete response. An 82-year-old man was referred for gastric cancer treatment. Contrast-enhanced computed tomography revealed stomach wall thickening and swollen left supraclavicular LN. This gastric cancer was assessed as unresectable due to the presence of Virchow's LNM; therefore, chemotherapy and ICI using S-1 plus oxaliplatin plus nivolumab were administered. After three courses of treatment, the primary tumor and Virchow's LN showed a marked reduction in size. The patient underwent Virchow's LNM resection as a preliminary step to determine indications for curative surgery. A pathological examination revealed no viable cancer cells were found inside the resected LN. The patient underwent distal gastrectomy. Pathological examination revealed complete degeneration of the primary tumor and regional LN without residual carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for one year after the initial treatment.

Evaluation of the Significance of Lymphatic, Microvascular and Perineural Invasion in Patients With Pancreatic Neuroendocrine Neoplasms.

Background: Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural invasion remains unclear. We aimed to clarify the role of these factors in PanNEN recurrence. Patients and Methods: We analyzed 138 patients who underwent curative pancreatectomy and were pathologically diagnosed with PanNEN. We evaluated the association between clinicopathological factors and the recurrence of PanNENs. Results: The numbers of patients with lymphatic, microvascular, and perineural invasion were 34 (25%), 43 (31%) and 17 (12%), respectively. Twenty-four patients (17%) had recurrences, and the 3, 5, and 10-year recurrence-free survival (RFS) rates were 88%, 84%, and 76%, respectively. The recurrence sites (with duplication) were mainly the liver (twenty-two patients), followed by the lymph nodes (seven patients), and bone (two patients). In multivariate analyses, grade 2-3 and the presence of microvascular invasion were significant risk factors for RFS (hazard ratio=7.5 and 7.9, respectively). When examining outcomes according to these factors, the 5-year RFS rates of patients with risk scores of 0, 1, and 2 were 100%, 91%, and 32%, respectively (p<0.001). Even in patients with grade 1 (n=97) or limited resection (enucleation, splenic-preserving distal pancreatectomy, central pancreatectomy, and duodenum-preserving pancreatic head resection, n=62), the presence of microvascular invasion was a significant risk factor for RFS (hazard ratio=13.4 and 18.0, respectively). Conclusion: The presence of microvascular invasion is an independent risk factor for recurrence in patients with PanNEN.

A case of pathologically complete response after preoperative chemotherapy in a pancreatic acinar cell carcinoma patient with portal vein tumor thrombosis.

Preoperative treatment is being proposed as a standard treatment for pancreatic ductal adenocarcinoma though few cases show a pathologically complete response. On the other hand, there is no consensus regarding preoperative chemotherapy for pancreatic acinar cell carcinoma (ACC). The present study described a rare case of ACC in the pancreatic head with portal vein tumor thrombosis (PVTT) treated with preoperative chemotherapy using modified FOLFIRINOX, which achieved a pathologically complete response. A 65-year-old man was referred for consideration of treatment strategy. Contrast-enhanced abdominal computed tomography revealed a pancreatic tumor and PVTT. The pancreatic tumor was diagnosed as ACC by an endoscopic ultrasound-guided fine-needle aspiration biopsy. Initially, the tumor was assessed as unresectable due to the presence of PVTT, and therefore, a chemotherapy using modified FOLFIRINOX was administered. After 14 courses of the chemotherapy, imaging studies revealed that the tumor and PVTT showed marked reduction in size; thus, the patient underwent pancreaticoduodenectomy with combined resection of the portal vein (PV). A pathological examination uncovered a complete degeneration of the primary tumor and the PV embolus without any residue of carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for 33 months after surgery. The chemotherapy using modified FOLFIRINOX could give a complete response in patients with pancreatic ACC with PVTT.

Hepatic artery resection without reconstruction in pancreatoduodenectomy.

PURPOSE: It has been reported that there are left and right hepatic arterial arcades via the blood vessels around the hilar bile duct; therefore, when the hilar bile duct is preserved, hepatic artery reconstruction may not be necessary. We compared the short-term and long-term outcomes in patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy (PD) with right hepatic artery resection without right hepatic artery reconstruction (RHAR group) with those patients who underwent conventional PD. METHODS: All data were retrospectively collected from patient records. A 1:4-propensity score-matched case-control study was conducted in patients with distal cholangiocarcinoma who received treatment at Tokyo Women's Medical University from February 1985 to April 2015. RESULTS: There was no statistical difference in the overall morbidity rate between the two groups. No patient in the RHAR group (10 patients) had liver failure, liver abscess, or cholangitis in the postoperative period; one patient died postoperatively because of a bleeding pseudoaneurysm in the gastroduodenal artery. The PD group (40 patients) had a significantly better median time regarding the recurrence (34 vs. 11 months, p=0.027) and 5-year disease-free survival (35% vs. 10%, p=0.027) rates than the RHAR group, which may be attributed to the presence of a more severe disease in patients in the RHAR group. CONCLUSION: We concluded that pancreaticoduodenectomy with right hepatic artery resection without reconstruction has a comparable overall morbidity rate with that of a conventional pancreaticoduodenectomy surgery and may be performed as an alternative procedure when tumor invasion of the right hepatic artery is suspected.

Impact of the controlling nutritional status score on severe postoperative complications of pancreaticoduodenectomy for pancreatic cancer.

PURPOSE: The controlling nutritional status (CONUT) score is a useful biomarker to evaluate undernutrition. However, there have been few reports describing the correlation between postoperative complications and the CONUT score for pancreatic cancer. Therefore, this study aimed to assess the impact of the CONUT score on the postoperative complications of pancreaticoduodenectomy (PD) in patients with pancreatic cancer. METHODS: We retrospectively analyzed 206 consecutive patients with pancreatic cancer who underwent PD over a 12-year duration at our institution. The patients were divided into two groups based on preoperative CONUT scores; their clinicopathological characteristics and surgical outcomes were compared. Furthermore, we compared the CONUT score with preoperative clinical factors and several nutritional biomarkers for postoperative complications using univariate and multivariate analyses. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ IIIa and those of Clavien-Dindo grade ≥ IIIb occurred in 29 (14.1%) and 9 (4.4%) patients, respectively. The high CONUT score (≥5) group indicated that patients with an undernutrition status had a higher postoperative complication rate, poorer relapse-free survival, and overall survival rates than the low CONUT score (≤4) group. Among preoperative clinical factors, a high CONUT score was an independent risk factor for severe postoperative complications. CONCLUSIONS: The CONUT score may be a useful parameter in the identification of patients undergoing pancreatic surgery who are susceptible to postoperative complications.

Evaluation of the validity of pancreatectomy for very elderly patients with pancreatic ductal adenocarcinoma.

PURPOSE: The role of pancreatectomy for very elderly patients with pancreatic adenocarcinoma is controversial. This study aimed to clarify the validity of pancreatic resection in octogenarian patients with pancreatic ductal adenocarcinoma. METHODS: We compared 31 patients aged ≥ 80 years and 548 patients aged < 80 years who underwent pancreatectomy for pancreatic ductal adenocarcinoma and evaluated the relationship between age, clinicopathological factors, recurrence, and outcomes. RESULTS: Postoperative mortality, morbidity, and completion of adjuvant chemotherapy rates did not differ between groups. There were no significant differences in median recurrence-free survival, disease-specific survival, and overall survival between groups (1.0, 2.3, and 2.2 years in patients ≥ 80 years and 1.2, 2.8, and 2.7 years in patients < 80 years; P = 0.67, 0.47, and 0.46, respectively). The median time from recurrence to death of octogenarian patients was significantly shorter than that of younger patients (0.6 vs. 1.1 years, P = 0.0070). In multivariate analysis, age ≥ 80 years (hazard ratio, 1.5), resection of other organs (hazard ratio, 1.8), pathological grade 2/3 (hazard ratio, 1.6), and failure to implement of treatment after recurrence (hazard ratio, 3.6) were independent risk factors for a short time from recurrence to death. Furthermore, age ≥ 80 years (odds ratio, 0.32) was an independent risk factor for the implementation of treatment after recurrence. CONCLUSIONS: Pancreatectomy for octogenarians may be acceptable, but median survival time from recurrence to death was shorter due to lower rates of implementation of treatment after recurrence in octogenarian patients.

Negative prognostic outcomes of percutaneous transhepatic biliary drainage in distal cholangiocarcinoma: a retrospective analysis using propensity score matching.

BACKGROUND: The efficacy of different types of preoperative biliary drainage for cholangiocarcinoma has been debated over the past two decades. Controversy concerning the use of percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD) still exists. This study aimed to compare the long-term outcomes between PTBD and EBD in patients with distal cholangiocarcinoma. METHODS: Data of patients diagnosed with distal cholangiocarcinoma who underwent preoperative PTBD or EBD from January 1999 to December 2017 were analyzed retrospectively. Post-surgical outcomes, including the incidence of post-operative complications, peritoneal metastasis, disease-free survival, and overall survival, were analyzed. Survival analyses were also performed after propensity score matching in the PTBD and EBD groups. RESULTS: The incidence of post-operative complications was similar in both groups. The 5-year estimated cumulative incidences for peritoneal metastasis were 14.7% and 7.2% in the PTBD and EBD groups, respectively (p = 0.192). The 5-year disease-free survival rates were 23.7% and 47.3% in the PTBD and EBD groups, respectively (p = 0.015). In the multi-variate analysis for overall survival, PTBD was an independent poor prognostic factor. The 5-year overall survival rates were 35.9% and 56.3% in the PTBD and EBD groups, respectively (hazard ratio 1.85, confidence interval 1.05-3.26, p = 0.035). The results after propensity score matching indicated a poorer prognosis in the PTBD group, with a 5-year survival rate of 35.9% in the PTBD group vs 56.0% in the EBD group (p = 0.044). CONCLUSION: PTBD should be considered as a negative prognostic factor in distal cholangiocarcinoma patients.

Drain Lipase Levels and Decreased Rate of Drain Amylase Levels as Independent Predictors of Pancreatic Fistula with Nomogram After Pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy (PD) has recently been improved due to its increased safety. However, postoperative pancreatic fistula (POPF) remains a lethal complication of PD. Identifying novel clinicophysiological risk factors for POPF during the early post-PD period would help improve patient morbidity and mortality. Therefore, this retrospective study aimed to evaluate possible risk factors during the early postoperative period after pancreaticoduodenectomy (PD). METHODS: Data from 349 patients who underwent PD between 2007 and 2012 were examined retrospectively. All patients were classified into 2 groups: group A, patients without fistulae or biochemical leaks (288 patients), and group B, those with grade B or C POPF (61 patients). Data on various clinicophysiological parameters, including serum and drain laboratory data, were collected. Univariate and multivariate analyses were performed to evaluate POPF predictors. A predictive nomogram was established for these results. RESULTS: Univariate analysis showed that various serum and drain-related factors, such as white blood cell count, C-reactive protein levels, drain amylase (DAMY) levels, and drain lipase (DLIP) levels, were possible POPF risk factors. Multivariate analysis confirmed that postoperative day (POD) 1 DLIP levels (hazard ratio, 15.393; p = 0.037) and decreased rate (POD3/1) of DAMY levels (hazard ratio, 4.415; p = 0.028) were independent risk factors. Further, POD1 DLIP levels and decreased rate of DAMY levels were significantly lower in group A than in group B. The accuracy of nomogram was 0.810. CONCLUSIONS: POD1 DLIP levels (> 245 U/mL) and decreased rate of DAMY levels (> 0.44) were POPF risk factors, making them possible biomarkers for POPF.

Evaluation of the significance of adjuvant chemotherapy in patients with stage â A pancreatic ductal adenocarcinoma.

BACKGROUND: Although adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC. METHODS: We retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively). RESULTS: The 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) < 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0-1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2-3 risk factors (high-risk group; n = 26) (80% vs. 23%; P < 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045). CONCLUSIONS: In stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.

Resectional surgery in gallbladder cancer with jaundice-how to improve the outcome?

PURPOSE: To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors. METHODS: A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature. RESULTS: The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-à-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien-Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD. CONCLUSION: M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

Narrowing of the remnant portal vein diameter and decreased portal vein angle are risk factors for portal vein thrombosis after perihilar cholangiocarcinoma surgery.

PURPOSE: To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma. METHODS: A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle < 100°, remnant portal vein diameter < 5.77 mm, main portal vein diameter > 13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p < 0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively. CONCLUSION: Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

Evaluation of Early Prognostic Factors in Patients With Pancreatic Ductal Adenocarcinoma Receiving Gemcitabine Together With Nab-paclitaxel.

Background: Gemcitabine together with nab-paclitaxel (GnP) has been shown to improve outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). However, the predictive markers for treatment effects remain unclear. This study aimed to identify early prognostic factors in patients with PDAC receiving GnP. Patients and Methods: We analyzed 113 patients who received GnP for PDAC and evaluated the relationship between clinical factors and outcomes. Results: The median survival time (MST) was 1.2 years. In multivariate analysis, baseline carbohydrate antigen 19-9 (CA19-9) ≥747 U/ml [hazard ratio (HR)=1.9], baseline controlling nutrition status (CONUT) score ≥5 (HR=3.7) and changing rate of CA19-9 after two GnP cycles ≥0.69 (HR=3.7) were independent risk factors for poor prognosis. When examining outcomes according to pre-chemotherapeutic measurable factors (baseline CA19-9 and CONUT), the MSTs of patients with pre-chemotherapeutic zero risk factors (pre-low-risk group, n=63) and one or more risk factors (pre-high-risk group, n=50) were 1.7 and 0.65 years (p<0.001), respectively. The MST for those with a changing rate of CA19-9 after two GnP cycles <0.69 and ≥0.69 was significantly different in both groups (2.0 and 1.2 years in the pre-low-risk group, p<0.001; 1.0 and 0.52 years in the pre-high-risk group, p<0.001). Conclusion: These results may be useful for decision-making regarding treatment strategies in patients with PDAC receiving GnP.

Prognostic Factors for Surgically Resected Intraductal Papillary Neoplasm of the Bile Duct: A Retrospective Cohort Study.

BACKGROUND: To date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors' experience at a single institution. METHODS: The study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors' institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses. RESULTS: More than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002). CONCLUSIONS: Evaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Comparison of Clinicopathological Features of Biliary Neuroendocrine Carcinoma with Adenocarcinoma.

OBJECTIVE: This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. METHODS: We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. RESULTS: Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, p = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, p = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, p = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, p < 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (p = 0.022, hazard ratio: 6.09). CONCLUSIONS: Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.

Evaluation of allowable pancreatic resection rate depending on preoperative risk factors for new-onset diabetes mellitus after distal pancreatectomy.

BACKGROUND: Although more patients have long-term survival after pancreatectomy, the details of pancreatogenic diabetes mellitus (DM) are still unclear. We aimed to investigate the incidence of new-onset DM (NODM) after distal pancreatectomy (DP) and to clarify the risk factors, including allowable pancreatic resection rate (PR), for NODM. METHODS: The incidence, onset time, and risk factors for NODM were retrospectively evaluated in 150 patients who underwent DP without preoperative DM and with >5 years of postoperative follow-up between 2005 and 2015. RESULTS: The incidence rate of NODM was 39%, and 60% of this incidence was noted within 6 months postoperatively. In the multivariate analysis, hemoglobin A1c ≥ 5.8% (odds ratio [OR] 7.6), impaired glucose tolerance and/or impaired fasting glucose (OR 4.2), homeostasis model assessment of insulin resistance ≥1.4 (OR 5.5), and insulinogenic index <0.7 (OR 3.9) were the preoperative risk factors for NODM. Based on these four preoperative risk factors of NODM, we made the new scoring system to predict the NODM after DP. The NODM incidence was 0%, 8%, 48%, 60%, and 86% in patients with risk scores 0 (n = 25), 1 (n = 36), 2 (n = 33), 3 (n = 35), and 4 (n = 21), respectively. PRs ≥42.1% and ≥30.9% were allowable in the preoperative risk-score 0-1 and 2-4 groups. In the former group, the NODM incidence for PR ≥ 42.1% and <42.1% was significantly different (20% vs 0%, P < 0.05). In the latter group, the NODM incidence for PR ≥ 30.9% vs <30.9% was significantly different (75% vs 23%, P < 0.05). CONCLUSIONS: We clarified the preoperative risk factors and allowable PR for NODM and recommended the use of a risk scoring system for predicting NODM preoperatively.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.