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The prognostic value of the perioperative carbohydrate antigen 19-9 (CA19-9) value and the prognostic relationship between the CA19-9 value and the surgical margin in extrahepatic cholangiocarcinoma (EHCC) have not been fully discussed.A total of 390 patients who underwent curative resection for EHCC between 2002 and 2018 were retrospectively analyzed. According to the perioperative CA19-9 value, patients were divided into three groups: preoperative normal (Normal, n = 178), preoperative high and postoperative normal (Normalization, n = 155), and preoperative high and postoperative high (Nonnormalization, n = 57). Survival was analyzed according to the perioperative CA19-9 value and surgical margin.The optimal cutoff value of CA19-9 was 37 U/mL. Overall survival (OS) was significantly stratified according to the perioperative CA19-9 value. The 5-y OS rates in the Normal, Normalization, and Nonnormalization groups were 53%, 38%, and 23%, respectively (The perioperative CA19-9 value was related to the prognosis of resectable EHCC. A preoperative CA19-9 value of ≥37 U/mL reflected systemic disease. R0 resection did not affect the survival in this patient group.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Background The 7th and 8th editions of the American Joint Committee on Cancer (AJCC) tumor (T) classification of distal cholangiocarcinoma (DCC), which are based on either layer or depth, may not accurately stratify patient survival. Methods A total of 121 patients who underwent resection for DCC between 2002 and 2016 were analyzed. The impact of the AJCC staging system on survival was examined and a new T classification was established based on independent prognostic factors. Results Regarding overall survival, the optimal depth of invasion (DOI) cut-off value (8 mm) was the only independent prognostic factor. Regarding the relapse-free survival (RFS), a DOI >8 mm, portal vein (PV) invasion, and duodenal or pancreatic invasion were independent prognostic factors. A new T classification was developed as follows: T1, no invasion of adjacent organs; T2, invasion of the duodenum or pancreas; T3, invasion >8 mm into the bile duct wall; and T4, invasion of the PV or arteries. There were no significant differences in RFS according to the 8th edition of the AJCC. However, significant differences were observed in the RFS between T1 and T2 and between T2 and T3. Conclusion A new T classification based on the layer and depth may be more feasible.

To the best of our knowledge, the prognostic impact of distal pancreatectomy (DP) for pancreatic body and/or tail cancer involving portal vein (PV) has not been analyzed.A total of 155 patients with pancreatic body and/or tail cancer who were eligible candidates for resection between 2002 and 2017 were analyzed.Twenty-seven patients had PV contact ≤180°. Fifteen patients underwent preoperative treatment; finally, 132 patients underwent DP, and 21 underwent DP with celiac axis resection. The overall survival (OS) of the PV contact group (n = 27, median survival time [MST], 25.6 months) was worse than the non-PV contact group (n = 128; MST, 58.4 months; P = 0.002); however, it was better than the unresectable group (MST, 14.2 months; P = 0.011). The OS of the PV contact with preoperative chemotherapy group (MST, not available) was comparable to the non-PV contact group and better than the PV contact without preoperative chemotherapy group (MST, 13.4 months; P = 0.017). The multivariate analysis identified PV contact ( P = 0.046) as one of the independent prognostic factors of OS.Pancreatic body and/or tail cancer contact with PV ≤180° should be considered borderline resectable because of poor survival.

To evaluate differences in the safety line of the future liver remnant plasma clearance rate of indocyanine green (RemK) necessary to prevent posthepatectomy liver failure (PHLF) associated with liver tumors and comorbidities. The subjects of this retrospective study were patients who underwent trisectionectomy, hemihepatectomy, or sectionectomy, other than left lateral sectionectomy, between 2011 and 2018, at the Shizuoka Cancer Center. We analyzed the risk factors for PHLF grades B and C and then evaluated the RemK in these groups, according to various risk factors. A total of 463 patients were selected for the analyses. Among the patients with PHLF grades B and C, those with diabetes mellitus (DM), liver cirrhosis (LC), or hepatocellular carcinoma (HCC) had significantly higher RemK than those without these diseases. Multivariate analysis identified RemK ≤ 0.078, DM, and creatinine clearance rate

The purpose of this study was to evaluate changes in the body composition and nutritional status after total pancreatectomy (TP). Consecutive 45 patients underwent TP between February 2003 and July 2018. Among them, 32 had computed tomography images available before TP and at 6 and 12 months after TP. The skeletal muscle index (SMI), visceral fat tissue index (VFI), and subcutaneous fat tissue index (SFI) were measured using images at each time. Body mass index (BMI), serum albumin levels (Alb), hemoglobin A1c levels (HbA1c), and daily insulin use were also recorded. There were significant reductions in SMI (median, 38.7 vs. 36.6 cm2/m2, P = 0.030), VFI (12.4 vs. 5.1 cm2/m2, P < 0.001), SFI (26.5 vs. 9.2 cm2/m2, P < 0.001), BMI (20.3 vs. 18.7 kg/m2, P < 0.001), and Alb (4.2 vs. 3.7 g/dL, P = 0.031) at 6 months after TP compared with preoperative period. HbA1c significantly increased at 6 months after TP compared with postoperative discharge (6.7 vs. 7.3%, P < 0.001). The daily insulin use significantly increased at 12 months after TP compared with 6 months after TP (22 vs. 26 units/day, P < 0.001), whereas there were no significant changes in other parameters. Significant losses in fat and skeletal muscle mass as well as the BMI and Alb occurred within the first 6 months after TP. A subsequent increase in the daily insulin use occurred during the next six months, which helped preserve the body composition.

The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM). This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared. Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors. The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM.

Aim Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) in Japan. However, the cause and prognosis of HCC may be dramatically changed by direct acting antiviral agents (DAAs). Although the 2015 nationwide survey used a large cohort, its findings may be outdated. The present study therefore aimed to show the latest outcomes by patients’ hepatitis virus infection status. Methods We included 552 patients who underwent hepatectomy for primary HCC between 2002 and 2018 and compared clinical factors between those treated before 2014 (n = 380) and after 2014 (n = 172), when DAAs became available. Results Distribution of hepatitis virus infection status between the two groups differed significantly (P, The present study showed that C‐HCC patients who underwent surgery after 2014, when DAAs became available, had significantly better relapse‐free survival than the C‐HCC patients who underwent surgery before 2014 (P = 0.032). However, relapse‐free survival did not significantly differ between the earlier and latter NBNC‐HCC patients. The present study suggested that treatment strategies for NBNC‐HCC should be established because the rate of NBNC‐HCC patients has increased, but their prognosis has not been improved.

No study has clarified the clinical significance of albumin–bilirubin (ALBI) grade in a large cohort of pancreatic cancer patients. A total of 1006 consecutive patients diagnosed with pancreatic cancer and deemed eligible for surgical resection were analyzed. The ALBI score was calculated as: ALBI score = (log10 bilirubin [µmol/L] × 0.66) + (albumin [g/L] × − 0.0852). ALBI grade was assigned as grade 1, 2a, 2b, and 3. ALBI grade 1 was assigned to the ALBI low group (N = 566), and grades 2a, 2b, and 3 to the ALBI high group (N = 440). The primary lesion could not be resected in 129 patients. Among all patients, overall survival (OS) was significantly worse in the ALBI high group than in the ALBI low group (P = 0.024). Overall, 877 patients underwent pancreatectomy. In these patients, the ALBI high group was associated with high CA19-9 level (P

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood. This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients. FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P

Lymph node metastasis (LNM) has been regarded as one of the prognostic factors in patients with ampulla of Vater carcinoma (AC). However, the consensus about an optimal cutoff value of the number of LNMs and the definition of the regional lymph nodes (RLNs) has not been achieved. This study included 114 consecutive patients who underwent pancreatoduodenectomy for AC between January 2002 and March 2019. The minimum p value approach for the greatest difference in the overall survival classified the number of LNM into none (N0, n = 66), from 1 to 2 (N1, n = 32), and ≥3 LNM (N2, n = 11) (p = 0.004). Distant LNM was defined as M1 (n = 5). Significant differences in relapse-free survival (RFS) were found between N0 and N1 (p

The clinical impact of abutment to an artery and its branch on resectability and prognosis in patients with borderline resectable pancreatic cancer is unclear. Patients diagnosed with borderline resectable pancreatic cancer due to artery abutment between April 2012 and December 2018 were enrolled. Contact between arteries and the tumour was assessed by computed tomography (CT). A primary lesion was resected in 63 patients (R group) and unresected in 19 patients (UR group). Overall survival (OS) was worse in the UR group than in the R group (P

Some clinical studies have suggested that metformin improved prognoses in several cancers. This study aimed to identify prognostic factors for pancreatic ductal adenocarcinoma (PDAC) and determine the utility of metformin administration. Between January 2007 and December 2015, 373 consecutive patients underwent curative surgery for PDAC. Among the patients, 121 were diagnosed as having diabetes mellitus (DM) before surgery. The characteristics and overall survival (OS) between patients with and without DM were compared retrospectively. Based on their metformin intake, patients with DM were divided into two groups. OS rates between patients with and without metformin intake were compared. Univariate and multivariate analyses were performed to identify prognostic factors for OS among all patients and those with PDAC and DM. No significant differences in the 5-year survival rates between patients with and without DM were observed. Among the 121 patients with DM, 18 received metformin and 103 did not (other medications group). The 5-year survival rate was significantly better in the metformin group than in the other medications group (66.7% and 24.4%, respectively; p = 0.034). Multivariate analysis identified pN1 (p = 0.002), metformin administration (p = 0.022), and microvascular invasion (p = 0.023) as independent prognostic factors for OS in the patients with DM. Matched-pair analysis showed that OS tended to be better in the metformin group than in the other medications group (p = 0.067). History of metformin intake may contribute to favorable prognosis in patients with PDAC and pre-existing DM.

Aim This study evaluated the effects of postoperative adjuvant chemoradiotherapy (A‐CRT) for positive hepatic ductal margin (HM+) in extrahepatic cholangiocarcinoma (EHCC). Methods Patients with EHCC who underwent surgical resection between 2002 and 2014 were included in this retrospective study. For patients with HM+, A‐CRT was conducted. The clinical effect of A‐CRT for HM+ on the survival and recurrence and prognostic factors of EHCC was reviewed. Results Among 340 patients, the hepatic ductal margin was negative in 296 and positive in 44. Of the 44 patients with HM+, 22 received postoperative A‐CRT, and 22 did not. Hepatic stump recurrence occurred in 19 patients. The incidence was significantly higher in patients with HM+ (20%, 9/44) than in those with negative hepatic ductal margin (HM−) (3%, 10/296) (P, Adjuvant chemoradiotherapy was delivered for positive hepatic ductal margin in cholangiocarcinoma. However, this treatment did not affect the survival or stump recurrence.

Biliary confluence is sometimes involved in colorectal liver metastasis (CRLM), and therefore bile duct resection (BDR) is occasionally necessary for complete resection. However, the utility of hepatectomy with combined BDR is unclear. The safety and survival outcome of hepatectomy with combined BDR for CRLM was assessed. Patients who underwent hepatectomy for CRLM between 2002 and 2017 were identified from a prospectively compiled database. Postoperative outcomes were compared between patients undergoing hepatectomy alone and with combined BDR for CRLM. A total of 734 patients who underwent hepatectomy for CRLM were included. Hepatectomy with combined BDR was performed in 16 (2.1%) patients. The postoperative complications rate (Clavien–Dindo ≥ 3) of patients undergoing hepatectomy with BDR was 31.2%, which was higher than that without BDR (P = 0.001) for CRLM. The mortality rate of surgery for CRLM was 0%. The 5- and 10-year relapse-free survival (RFS) rates for hepatectomy with BDR were 45.0% and 30.0%, respectively. Patients undergoing hepatectomy with BDR had a similar RFS to those without BDR for CRLM (P = 0.351). The 5- and 10-year overall survival (OS) rates for hepatectomy with BDR were 62.6% and 62.6%, respectively. Patients undergoing hepatectomy with BDR had a similar OS to those without BDR for CRLM (P = 0.738). In conclusion, hepatectomy with combined BDR was a potentially feasible treatment option that obtained favorable survival outcomes in patients with invasion of the biliary confluence by CRLM, although BDR with hepatectomy for CRLM was associated with a high rate of morbidity.

Several indicators of systemic inflammation and nutritional status were recently shown to serve as novel prognostic factors for certain cancers. Here, we aimed to investigate the prognostic impact of preoperative indicators of systemic inflammation and nutritional status associated with the survival of patients with resected ampulla of Vater carcinoma (AC). We retrospectively analyzed the records of 91 patients who underwent pancreatoduodenectomy (PD) for AC from January 2002 through December 2018. Indices for systemic inflammation and nutritional status (Systemic immune-inflammation index [SII], Prognostic nutritional index [PNI], modified Glasgow prognostic score [mGPS], and Controlling nutritional status score [CONUT]) were determined using preoperative blood tests. Clinicopathological factors and these indices were analyzed to identify predictors of overall survival (OS). The median preoperative SII and PNI values were 456.7 and 47.5, respectively, and their optimal cut-off values were 670.0 and 50.0, respectively. Univariate analysis revealed that high SII, low PNI, mGPS ≥ 1, and malnutrition, assessed using the CONUT, were significant predictors of shorter OS. Multivariate analysis revealed that high SII (HR = 2.71, p = 0.023) and malnutrition assessed using the CONUT (hazard ratio = 3.98, p = 0.006) were independent predictors of shorter OS. SII and the CONUT predicted the survival of patients with AC after radical resection. These indicators are easily calculated using preoperative blood tests and may contribute to the development of improved strategies to treat AC.

Postoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM).Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS).One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004).Among the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors.

Adenosquamous carcinoma (ASC) of the pancreas is a rare malignancy, associated with a poor prognosis after surgical resection, with reported median survival times (MSTs) ranging from 4.4 to 13.1 months. We conducted this study to investigate the long-term outcomes of patients after the resection for ASC.Between 2002 and 2016, a total of 456 patients underwent resection for ASC or adenocarcinoma (AC) of the pancreas. ASC was confirmed in 17 (3.7%) of these patients. We analyzed the clinicopathological characteristics and survival of these 17 patients in comparison with those of patients with AC of the pancreas.The operative procedures performed were pancreaticoduodenectomy (n = 6) and distal pancreatectomy (n = 11). Seven (41.2%) of the 17 patients underwent combined organ resection. R0 resection was achieved in 16 (94.1%) patients. The 5-year overall survival (OS) rate and MST were 40.3% and 20.9 months, respectively. A squamous component of ≥ 60% (P = 0.001) and R1 resection (P 0.001) were significantly associated with poor OS for patients with ASC CONCLUSION: This study revealed longer survival and a higher R0 resection rate after aggressive combined resection in our ASC patients than those in previous studies. Although this was only a small series, our findings suggest that local control with aggressive resection may be an effective treatment protocol for ASC patients.

Background The classification of intrahepatic cholangiocarcinomas (ICCs) has been reported in several studies, however, it remains controversial. Materials and methods Between January 2003 and December 2015, 94 patients underwent hepatectomy for ICC. The ICCs of 63 of these patients were classified as predominantly small bile duct type or bile ductular type ICC and were included in this analysis. Results Thirty-seven patients (58.7%) were classified into the small bile duct ICC group, and 26 (41.3%) into the bile ductular ICC group. A multivariate analysis identified intrahepatic metastasis [hazard ratio (HR)=2.53, p=0.011], small bile duct ICC (HR=2.05, p=0.046) and portal vein invasion (HR 2.05, p=0.047) as independent prognostic factors for poorer survival. Conclusion It is important to correctly distinguish between small bile duct and bile ductular ICC types because these two types clearly have different clinicopathological and prognostic features.

This study aimed to develop the prognostic score (PS) based on clinical factors to stratify the prognosis in borderline resectable pancreatic cancer (BRPC) patients treated with neoadjuvant therapy (NAT).This retrospective study included 57 BRPC patients who received NAT between April 2012 and December 2017. A score was assigned to each prognostic factor available before and after NAT, according to their β coefficients.Multivariate analysis identified the following six prognostic factors, and scores were assigned as follows: being a familial PC patient (HR 4.98, p = 0.029), post-NAT CA19-9 ≥37 U/ml (HR 3.08, p = 0.020), reduction rate of CA19-970% (HR 3.71, p = 0.008), pre-NAT neutrophil-to-lymphocyte ratio ≥2.8 (HR 4.32, p = 0.003), and non-resection (HR 3.98, p = 0.009) were scored as 1; and post-NAT albumin-to-globulin ratio1.33 (HR 8.31, p 0.001) was scored as 2. The PS was calculated by summing the scores assigned to each prognostic factor. Patients were then classified into three risk groups (low- [0-1 points], moderate- [2-3 points], and high-risk [4-6 points] groups). Median overall survival in the low-, moderate-, and high-risk groups were not reached, 37.5 months, and 11.8 months, respectively, and there were significant differences in survival among the three groups (p 0.01 in each group).This study showed that the PS may be useful for predicting the prognosis of BRPC patients treated with NAT.

The systemic immune-inflammation index (SII) is a new marker, defined as the platelet count × neutrophil-to-lymphocyte ratio. This study evaluates the SII as a prognostic marker for the overall survival (OS) of patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma (DCC). One hundred and forty patients who underwent PD for DCC between September, 2002 and December, 2015 at our hospital were divided into a low SII (SII

A 77-year-old woman with a solitary existence was referred to our hospital for the treatment of pancreatic tumors. Computed tomography revealed an 18-mm mass in the pancreatic head that had invaded the right side of the superior mesenteric vein (SMV) and a 32-mm mass in the pancreatic tail. We performed middle segment-preserving pancreatectomy (MSPP) with SMV resection and reconstruction. The TNM classifications were T2, N1, M0, stage IIB in the pancreatic head, and T2, N0, M0, stage IB in the pancreatic tail, respectively. Postoperatively, the blood glucose was well controlled using only hypoglycemic drug, and insulin preparation was not necessary. No fatty diarrhea was found using a pancreatic enzyme supplement. After 9 months of follow-up, no recurrence was found. MSPP for pancreatic head and tail carcinomas seemed acceptable for both preserving the postoperative quality of life and ensuring curative resection especially in elderly patient with a solitary existence.

Background Hepatectomy with extrahepatic bile duct resection is associated with a high risk of posthepatectomy liver failure (PHLF). However, the utility of the remnant liver volume (RLV) in cholangiocarcinoma has not been studied intensively. Methods Patients who underwent major hepatectomy with extrahepatic bile duct resection between 2002 and 2018 were reviewed. The RLV was divided by body surface area (BSA) to normalize individual physical differences. Risk factors for clinically relevant PHLF were evaluated with special reference to the RLV/BSA. Results A total of 289 patients were included. The optimal cut-off value for RLV/BSA was determined to be 300 ml/m2. Thirty-two patients (11.1 per cent) developed PHLF. PHLF was more frequent in patients with an RLV/BSA below 300 ml/m2 than in those with a value of 300 ml/m2 or greater: 19 of 87 (22 per cent) versus 13 of 202 (6.4 per cent) (P, The present study showed the importance of considering the remnant liver volume (RLV) / body surface area (BSA) in addition to indocyanine green test for hepatectomy with extrahepatic bile duct resection. An RLV/BSA of 300 mL/m2 is a simple and useful cut-off value to predict posthepatectomy liver failure in patients who undergo major hepatectomy for cholangiocarcinoma. Remnant liver volume normalized using body surface area is a potential tool for predicting postoperative liver failure.

(Background)Recent studies have revealed that colorectal cancer (CRC) displays intratumor genetic heterogeneity, and the cancer microenvironment play an important role in the proliferation, invasion, and metastasis of CRC.(Methods)We performed genomic analysis on 22 paired patients with primary CRC and synchronous colorectal liver metastasis (CRLM) using whole-exome sequencing, cancer gene panels, and microarray gene expression profiling. In addition, immunohistochemical analysis was used to confirm the protein expression of genes identified as highly expressed in CRLM by DNA microarray analysis.(Results)A total of 22 paired patients were enrolled in this study, including 13 (59.1%) colon and 9 (40.9%) rectal cancer patients. All patients had synchronous liver metastasis and did not have any other extrahepatic metastases. We identified 11 probes (10 genes) that were highly expressed in CRLM compared to CRC, from 36022 probes obtained from primary CRC, CRLM, and normal liver tissues, using gene expression analysis with DNA microarray. Of the 11 probes (10 genes), 5 genes classified as encoding “matricellular proteins” (osteopontin, periostin, thrombospondin-2, MGP, and GPNMB) were selected for immunohistochemical analysis.Osteopontin was strongly expressed in CRLM (6 of 22 cases: 27.3%) but not in CRC (0 of 22: 0%; p=0.02). Periostin also showed strong immunoreactivity in CRLM (17 of 22: 68.2%) compared to 7 of 22 (31.8%) in CRC (p=0.006). Thrombospondin-2 showed strong immunoreactivity both in CRC and CRLM (54.5% in CRC, 45.5% in CRLM; p=0.55). GPNMB and MGP were rarely positive for both CRC and CRLM. A comparison of immunoreactive positive factors for these 5 genes revealed the complexities of gene expression in CRLM. Of the cases, 16 (72.7%) CRC revealed zero or only one positive immunoreactivity. On the other hand, CRLM revealed more frequent multiple immunoreactivity; 16 cases (72.7%) shared 2 or more factors, which was statistically more frequent in CRLM than in CRC (p=0.007).(Conclusions)This study revealed the genomic heterogeneity between paired primary CRC and CRLM in terms of cancer cell microenvironment. This finding will lead to new diagnostic and therapeutic targets in the era of genome-guided personalized cancer treatment.(Trial registration)This study was retrospectively registered.

Background Latent pancreatic fistula (LPF) is difficult to diagnose during the early postoperative phase because of initially normal drain fluid amylase (DFA) levels. The present study investigated the clinical significance and risk factors of LPF after pancreatoduodenectomy. Methods A total of 662 patients who underwent pancreatoduodenectomy between 2010 and 2018 were retrospectively analyzed. LPF was defined as pancreatic fistula that developed later regardless of initially low DFA levels. Results Among the 372 patients with DFA ≤375 U/L (three times the upper limit for serum) on postoperative day (POD) 3, LPF occurred in 37 (10%). The rates of postoperative hemorrhaging (11% vs 1.5%), intraabdominal abscess (57% vs 7.2%) and reintervention (46% vs 2.7%) were significantly higher in the patients with LPF than in those without LPF. A multivariate analysis revealed that a body mass index ≥25 kg/m2 , a non-combined portal vein resection, a DFA on POD 1 ≥650 U/L and a C-reactive protein level on POD 3 ≥11 mg/dL were independent risk factors for LPF. Conclusions Latent pancreatic fistula was significantly associated with severe complications and worse outcomes after pancreatoduodenectomy. Early drain removal may be unfavorable for patients with some of these risk factors.

The controlling nutritional status (CONUT) score can be easily calculated from the serum albumin concentration, total cholesterol concentration, and total lymphocyte count. The study aim was to assess the preoperative prognostic factors for the overall survival (OS) of distal cholangiocarcinoma (DCC) following pancreatoduodenectomy (PD) and to demonstrate the utility of the CONUT score. A total of 149 consecutive patients who underwent PD for DCC between September 2002 and December 2016 were divided into a low-CONUT (LC) group (CONUT scores ≤ 2) and a high-CONUT (HC) group (CONUT scores ≥ 3). The clinicopathological characteristics and OS of the patients were evaluated retrospectively. Prognostic factors of DCC were identified by multivariate analyses. The LC and HC groups included 113 and 36 patients, respectively. The OS was better in the LC group than in the HC group (median survival time and 5 year survival rate: 82 months and 56.8% vs. 38 months and 27.6%, P = 0.005). Multivariate analyses for the OS in all patients showed that the tumor differentiation, perineural invasion, residual tumor status, portal vein resection, blood transfusion, and preoperative CONUT score ≥ 3 were independently associated with a poor survival. The CONUT score may be a useful preoperative factor for predicting the long-term survival in patients with DCC.

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI P = 0.011) and a carbohydrate antigen (CA) 19–9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73–25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.

Lymph node metastasis is one of the strongest prognostic factors of pancreatic cancer. However, the clinical implication of pathologically node-negative pancreatic cancer (pN0-PC) has not been fully investigated. Patients who underwent surgical resection for radiologically resectable pancreatic cancer between 2002 and 2018 were included in this study. A clinicopathological examination focusing on pN0-PC was performed. Of all 533 patients, 155 (29.1%) were diagnosed with pN0-PC and 378 (70.9%) were diagnosed with node-positive pancreatic cancer (pN1/2-PC). The 5-year survival rates of patients with pN0-PC and pN1/2-PC were 57.1% and 25.0%, respectively (p

The prognostic factors for duodenal carcinoma (DC) remain unclear because of its rarity. This study aimed to investigate the prognostic impact of pancreatic invasion (PI) on postoperative survival for patients with DC. This study retrospectively analyzed 86 patients with DC, including 18 patients with PI, who underwent surgical resection between October 2002 and March 2018. The clinicopathologic features and survival outcomes of these patients were investigated to identify the prognostic factors in DC. The long-term survival for the DC patients with PI was compared with that for the patients who underwent resection for resectable pancreatic head carcinoma (RPHC) during the same period. The median survival time (MST) for the DC patients with PI was 25.7 months, which was significantly worse than for the patients with T2 or deeper DC without PI (p = 0.010). The multivariate analysis showed that the independent prognostic factors were PI (hazard ratio [HR] 7.59; p = 0.019) and lymph node metastasis (LNM) (HR 5.01; p = 0.026). The MST for the DC patients with PI did not differ significantly from that for the RPHC patients treated without adjuvant chemotherapy (p = 0.135). Comparable rates of microscopic venous invasion and hematogenous metastasis were observed for the DC patients with PI and the RPHC patients. Pancreatic invasion was an independent prognostic factor in DC. The survival outcomes for the DC patients with PI did not differ from those for the patients with RPHC, which was associated with a high rate of hematogenous recurrence.

Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history. This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging. MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27 mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27 mm) in HCC with a treatment history was smaller than in primary HCC (37 mm). The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history.

Background Circumportal pancreas (CP) is an anatomical anomaly in the form of abnormal parenchymal fusion between the uncinate process and the pancreatic body, and it requires an additional parenchymal dissection during pancreaticoduodenectomy (PD). This study aimed to investigate the prevalence of CP in PD and to evaluate the incidence of postoperative pancreatic fistula (POPF) among CP patients. Methods Patients who underwent PD from 2002 to 2012 (n = 552) were included. Operative records and preoperative images were independently reviewed to identify the presence of CP. The incidence of POPF was compared between CP and non-CP patients and was evaluated via multivariate analysis. Results CP was confirmed from operative records in 7 (1.3%) patients, and abnormal parenchymal fusion was identified from preoperative images in 8 (1.4%) patients. The incidence of POPF was significantly higher in CP patients than in non-CP patients (71% vs 32%, P = 0.039). On multivariate analysis, CP was an independent predictive factor for POPF (odds ratio, 9.97; 95% confidence interval, 1.76–56.6; P = 0.009). Discussion Surgeons should heed the presence of CP in PD because this rare anomaly requires an additional parenchymal dissection and may increase the incidence of POPF.

// Ryo Ashida 1 , Yukiyasu Okamura 1 , Keiichi Ohshima 2 , Yuko Kakuda 3 , Katsuhiko Uesaka 1 , Teiichi Sugiura 1 , Takaaki Ito 1 , Yusuke Yamamoto 1 , Takashi Sugino 3 , Kenichi Urakami 4 , Masatoshi Kusuhara 5 and Ken Yamaguchi 6 1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan 2 Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan 3 Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan 4 Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan 5 Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan 6 Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan Correspondence to: Yukiyasu Okamura, email: yu.okamura@scchr.jp Keywords: hepatocellular carcinoma; integrated gene expression profiling; CYP2C19 gene; down-regulation; recurrence-free survival Received: February 05, 2018 Accepted: April 05, 2018 Published: April 24, 2018 ABSTRACT Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues. The GEP analysis showed that the down-regulated genes in tumor tissue were CYP3A4 in 56 patients (61%), CYP2C8 in 44 patients (48%), CYP2C19 in 30 patients (33%), CYP2D6 in 11 patients (12%), CYP3A5 in 7 patients (8%) and CYP1B1 in 2 patients (2%). There was no patients with down-regulation of the CYP17A1 gene. A multivariate analysis revealed that the presence of microscopic portal invasion (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.30–5.05 P = 0.006), the presence of intrahepatic-metastasis (HR 3.09 95% CI 1.52–6.29 P = 0.002) and down-regulation of the CYP2C19 gene (HR 3.69 95% CI 1.83–7.46 P < 0.001) were independent predictors for the recurrence-free survival (RFS). The down-regulation of the CYP2C19 gene were correlated with the RFS in HCC.

The indication of surgery in intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM), macroscopic periductal infiltration (PI), and intrahepatic metastasis (IM) remains unclear.Patients who underwent resection for mass-forming (MF) dominant ICC and unresected patients caused by LNM, IM, or locally advanced tumors (UR group) were enrolled. The significance of CA19-9 was investigated in advanced ICC.Seventy-three patients who underwent resection and 20 UR patients were analyzed. Using the minimum p value approach based on the overall survival, the optimal CA19-9 cutoff value was 300 U/mL. The OS of the patients with CA19-9 37 U/mL (n = 26; MST, 49.6 months) and 37-300 U/mL (n = 28; MST, 45.1 months) was comparable (P = 0.842); however, the OS of the patients with CA19-9 = 37-300 U/mL was significantly better than that with CA19-9 ≥ 300 U/mL (n = 19; MST, 15.3 months; P 0.001). CA19-9 300 U/mL, MF + PI, and IM were independently associated with OS. The OS of the patients with CA19-9 300 U/mL who developed LNM (MST, 34.0 months), MF + PI (MST, 32.9 months), or IM (MST, 35.2 months), or who required major vascular resection (MST, 45.1 months) was better than those with CA19-9 ≥ 300 U/mL who developed LNM (MST, 8.7 months; P = 0.005), MF + PI (MST, 7.5 months; P = 0.040), or IM (MST, 8.7 months; P = 0.001), or who required major vascular resection (MST, 14.8 months; P = 0.015); their prognosis was similar with the UR group.Even if patients had ICC developing LNM, PI, or IM, or require major vascular resection, surgical resection can be indicated for patients with CA19-9 300 U/mL. However, the indications for either adjuvant therapy or resection should be carefully determined in patients with CA19-9 ≥ 300 U/mL.

Background: With aging populations increasing in developed countries, the prevalence of elderly patients with hepatocellular carcinoma (HCC) is expected to rise. The aim of this study was to determine the short- and long-term outcomes of HCC surgery in elderly patients (≥75 years) using propensity score matching. Methods: The study group included 421 patients who underwent hepatectomy as their initial treatment with curative intent. The patients were divided into elderly (n = 111) and non-elderly (n = 310) groups. We applied propensity score matching – taking into consideration patient background, blood examination, and tumor factors – to minimize the effect of potential confounders. We then compared the results before and after the propensity matching. Results: Before propensity matching, the elderly group included significantly more patients with a high American Society of Anesthesiologists physical status (p < 0.001). In addition, they were taking antihypertensive drugs or an anticoagulant (both p < 0.001). The severe postoperative complications and the overall survival rates for these elderly patients were significantly poorer than for the non-elderly patients (p = 0.015 and p = 0.030, respectively). We then chose 70 patients from each group for whom the preoperative confounding factors were balanced and compared the two groups. The factors identified before matching (severe complications and overall survival rates) were no longer relevant, i.e. there were no significant differences between the two groups. Conclusion: Hepatectomy for HCC in elderly patients is justified.

Background/Aims: Several tumor factors seem to be related to the hepatocellular carcinoma (HCC) prognosis, but they are not definitive, except for major vascular invasion. We analyzed the impact of serosal invasion, which is histologically classified into four groups according to the definition of the Liver Cancer Study Group of Japan - S0: no tumor invasion of serosa, S1: tumor invasion of serosa, S2: tumor invasion of adjacent organs, S3: tumor rupture with intraperitoneal bleeding. Methods: This retrospective study included 421 consecutive patients who underwent hepatectomy as an initial treatment for HCC between September 2002 and December 2014. Results: Kaplan-Meier analysis and log-rank tests revealed that both recurrence-free survival (RFS) and disease-specific survival (DSS) worsened as the serosal invasion status advanced. Multivariate analyses showed that S2/S3 was independently correlated with RFS (hazard ratio [HR] 3.52; p < 0.001) and DSS (HR 2.58; p = 0.039). Another multivariate analysis showed that serosal invasion (S1-S3) was independently correlated with RFS (HR 1.70; p = 0.015) but not with DSS (HR 1.38; p = 0.27). Conclusion: Invasion to adjacent organs and tumor rupture were crucial prognostic factors for both DSS and RFS. Serosal invasion was an independent prognostic factor only for RFS.

Some reports have stated that pancreatoduodenectomy for elderly patients have comparable morbidity and mortality to that of young patients. However, the long-term outcomes of these patients have not been fully evaluated, especially for pancreatic head cancer. A total of 227 patients who underwent pancreatoduodenectomy for pancreatic head cancer between 2007 and 2014 were included. They were stratified according to age: young (

It remains controversial whether the degree of venous involvement really is associated with borderline resectability of pancreatic cancer. A single-center retrospective review of patients who underwent upfront pancreaticoduodenectomy for T3 pancreatic cancer without arterial involvement was performed. The patients were classified as having resectable tumors without venous contact (R group), resectable tumors with venous contact of 180° or less (R-PV group), and borderline resectable tumors with venous contact greater than 180° (BR-PV group). The unresectable group included those who had unresected tumors with paraaortic lymph node metastasis, positive peritoneal lavage cytology, or locally advanced disease. The overall survival and prognostic factors were analyzed. The study enrolled 299 resected patients, including 141 patients in the R group, 119 patients in the R-PV group, and 39 patients in the BR-PV group. The overall survival did not differ significantly between the R-PV group and the BR-PV group (median survival, 20.7 vs 18.6 months; P = 0.807). Among the 158 patients who had tumors with venous contact, only a tumor size of 50 mm or larger (P = 0.041) was an independent prognostic factor in a multivariate analysis, and the overall survival for the patients with both venous contact and tumor size 50 mm or larger was comparable with that for the unresectable group (P = 0.547). The degree of venous involvement may not be associated with the resectability of pancreatic head cancer, whereas tumors 50 mm in size or larger that develop venous invasion may be categorized as borderline resectable pancreatic cancers.

Background: There are a few reports that compare the rate of postoperative complications between subtotal stomach-preserving pancreatoduodenectomy (SSPPD) and antrectomy-combined pancreatoduodenectomy (ACPD), especially with respect to delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). Methods: From 2002 to 2013, 628 patients who underwent SSPPD (n = 78) or ACPD (n = 550) were enrolled in this study. The rate of DGE and the nutritional status were compared between patients receiving ACPD and SSPPD. Results: The overall morbidity rate (p = 0.830) was comparable between both groups; however, the incidence of DGE grade B or C was significantly higher in the SSPPD group than that in the ACPD group (16 vs. 7%, p = 0.007). A multivariate analysis identified SSPPD rather than ACPD (p = 0.007) and portal vein resection and reconstruction (p = 0.028) to be independent risk factors for DGE grade B or C. The changes in the body weight and nutritional parameters 3, 6, and 12 months after surgery were comparable between 2 groups. Conclusions: SSPPD and not ACPD was an independent risk factor for grade B or C DGE, but the postoperative nutritional status was comparable between the 2 groups based on the limited nutritional data. Combined resection of antrum will help reduce the risk of DGE after PD.

Gastroenterostomy and stent placement are the most common palliative procedures for patients with a gastric outlet obstruction caused by advanced pancreatic adenocarcinoma. Gastroenterostomy is regarded as the optimum treatment for patients in whom a longer survival is expected, while stent placement is preferred for patients whose survival is likely to be relatively short. However, prognosis of such patients has not been fully evaluated.This study included patients undergoing gastroenterostomy or duodenal stent placement for gastric outlet obstruction caused by advanced pancreatic adenocarcinoma between 2002 and 2015. Prognostic factors found to be significant based on a multivariate analysis were given a prognostic score according to their hazard ratios (HR). The overall survivals stratified according to the total prognostic score were compared.The median survival time of all cohorts was 4.2 months. The multivariate analyses demonstrated a neutrophil-to-lymphocyte ratio (NLR) ≥ 4 (HR = 4.01, p 0.001), presence of liver metastases (HR = 1.90, p = 0.002), and presence of cancer pain (HR = 2.08, p 0.001) to be significant prognostic factors. Regarding the HR, NLR ≥ 4, liver metastases and cancer pain were subsequently scored as 2, 1, and 1, respectively. The median survival time was 9.4 months in patients with a score of 0 or 1 and 3.3 months in patients with a score of 2-4, respectively.The scoring system clearly demonstrates the patient survival. Patients with scores of 0 or 1 are favorable candidates for gastroenterostomy, while patients with scores of 2-4 are candidates for stent placement.

A duodenal polyp was found during a health check of a 71-year-old asymptomatic man. Duodenoscopy demonstrated a pedunculated, smooth-surfaced tumor of 18 mm in size, protruding from the minor papilla. Endoscopic ultrasonography demonstrated a homogeneously low-echoic submucosal tumor. Enhanced computed tomography and magnetic resonance imaging demonstrated a well-enhanced duodenal tumor without obvious metastasis. A tumor biopsy revealed a well-differentiated neuroendocrine tumor, and laparotomic transduodenal polypectomy with regional lymph node dissection was performed. The histology of the surgical specimen revealed gangliocytic paraganglioma consisting of three cell types: endocrine, ganglion, and spindle cells. There has been no recurrence in >5 years after surgery.

Background: Selecting patients who will benefit from resection among those with advanced gallbladder cancer (GBCa) having poor prognostic factors is difficult. Methods: One hundred twenty-one patients who underwent resection for stage II–IV GBCa and 19 unresected patients (unresectable group) were enrolled. The clinical impact of carbohydrate antigen 19-9 (CA19-9) and advanced surgical procedures for GBCa was evaluated. Results: The optimal CA19-9 cutoff value (based on the greatest difference in overall survival) was 250 U/mL. CA19-9 ≥250 U/mL was found to be an independent prognostic factor. Patients with CA19-9 p = 0.061) or who required major hepatectomy (MST, 9.2 months; p = 0.066) or PD (MST, 8.6 months; p = 0.025); their prognosis was comparable to that of the unresectable group (jaundice: p = 0.145, major hepatectomy: p = 0.292, PD: p = 0.756). Conclusions: Even if GBCa patients develop jaundice or require major hepatectomy, or combined PD, resection can be considered for those with CA19-9

There are many treatment choices for hepatocellular carcinoma (HCC), one of which is proton beam therapy (PBT). The purpose of this study was to compare surgical resection (SR) and PBT to clarify the prognostic factors for operable HCC based on a single institution’s database. Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status were excluded. There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099). The RFS was comparable between the PBT and SR groups. However, the PBT group had a significantly worse overall survival than the SR group. SR may therefore be favorable as an initial treatment for HCC compared to PBT.

Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC). Achieving a sustained virological response (SVR) is associated with a reduced risk of recurrence. The recent introduction of direct acting antivirals (DAAs) has resulted in SVR rates of nearly 100% in treated patients. The purpose of the present study was to clarify the outcomes in patients who underwent antiviral therapy and patients without antiviral therapy. This retrospective study included 220 patients with primary HCV-related HCC who underwent hepatectomy. An SVR was defined as a serum HCV-RNA titer below the detection sensitivity limit at 6 months after the termination of antiviral therapy. Postoperative antiviral therapy was introduced after confirming that there was no early recurrence. Eighty-eight patients received antiviral therapy. Among these, 58 patients (66%) obtained an SVR. With the exception of one patient, all patients who received DAAs obtained an SVR. The overall survival rate of the pre-operative SVR group was significantly better than that of the preoperative untreated group (P = 0.045). Moreover, there was no recurrence at 3 years after surgery in the pre-operative SVR group. The achievement of an SVR was an independent predictor of overall survival [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59–0.94, P = 0.011] and recurrence (HR 0.61, 95% CI 0.40–0.94, P = 0.024). Obtaining an SVR either before or after surgery was associated with the suppression of HCC recurrence after hepatectomy in patients with primary HCV-related HCC.

The objective was to clarify the prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) of intrahepatic cholangiocarcinoma (ICC). A total of 103 ICC patients who underwent hepatectomy between 2002 and 2016 were enrolled. The survival impact of AJCC/UICC 8th edition was examined. The 5-year disease-specific survival (DSS) rate was 75.9% in T1a (n = 23), 88.9% in T1b (n = 10), 14.9% in T2 (n = 24), 52.5% in T3 (n = 11), and 15.2% in T4 (n = 35). The DSS was comparable among T2, T3, and T4 (T2 vs. T3; p = 0.345, T3 vs. T4; 0.295). A multivariate analysis identified multiple tumors (hazard ratio [HR] 2.821), periductal infiltrating (HR 2.439), perforation of the visceral peritoneum (HR 1.850), and vascular invasion (HR 1.872) as independent prognostic factors that were associated with the DSS. The optimum tumor size with the greatest difference in the DSS was 2 cm (p = 0.014). The new T classification was developed as follows: T1, size ≤ 2 cm without other factors; T2, size > 2 cm without other factors; T3, vascular invasion or perforation of the visceral peritoneum; and T4, multiple tumors or periductal infiltrating. The 5-year DSS was 100% in T1 (n = 7), 76.6% in T2 (n = 28), 45.1% in T3 (n = 28), and 3.4% in T4 (n = 40). There were differences in the DSS between T2 and T3 (p = 0.035) and between T3 and T4 (p = 0.003). T2, T3, and T4 of AJCC/UICC overlapped with regard to the DSS. The new staging can classify ICC patients with sufficient prognostic differences.

Background No reports have so far described arteriovenous malformation (AVM) in the pancreas caused by a tumor. We herein report a case of pancreatoduodenectomy for a patient who developed duodenal hemorrhage due to AVM developed around serous cystic neoplasm (SCN) of the pancreas. Case presentation A 79-year-old man was referred to our hospital because of anemia (Hb 7.4 g/dl) and pancreatic head tumor. Computed tomography showed microcystic-type SCN, 87 mm in size, in the pancreatic head. Vascular hyperplasia had developed around the cystic lesion. Upper gastrointestinal endoscopy and colonoscopy did not reveal the cause of anemia, so the patient was followed closely without hemostatic therapy. Iron preparations had improved the anemia. Three months later, the patient developed anemia (Hb 5.8 g/dl) again. Gastrointestinal endoscopy showed oozing from the mucosa in the duodenum via the swollen vascular hyperplasia. He was diagnosed as duodenal hemorrhage from the blood vessels around SCN. Pancreatoduodenectomy was performed to control repeated duodenal bleeding. A histopathological examination revealed that the cystic lesion in the pancreatic head was SCN, and the AVM developed around SCN and duodenum, causing repeated duodenal hemorrhage. The patient was discharged on postoperative day 22. Nine months after surgery, the patient had no recurrence of anemia. Conclusions There have been no reports of duodenal hemorrhage due to acquired pancreatic AVM around pancreatic tumor, including SCN. We successfully treated a case of duodenal hemorrhage due to pancreatic AVM around SCN by pancreatoduodenectomy.