BEX2 is poor prognostic factor and required for cancer stemness in gastric cancer.

Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target.

Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer.

BACKGROUND: Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. METHODS: We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. RESULTS: The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). CONCLUSIONS: These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.

BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.

Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein.

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.

Fibroblast growth factor receptor 2 (FGFR2) fusions in Japanese patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Fibroblast growth factor receptor gene alterations have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer that has a poor prognosis. This study evaluated the frequency of fibroblast growth factor receptor 2 fusions in clinical specimens from Japanese patients with iCCA. METHODS: This study enrolled 116 patients who had histologically or cytologically confirmed adenocarcinoma and been diagnosed as relapsing after resection or with unresectable intrahepatic cholangiocarcinoma. We evaluated the frequency of fibroblast growth factor receptor 2 fusions-positive cells in their specimens using break-apart fluorescent in situ hybridization 'for 114 patients who met the study protocol'. RESULTS: Of a total of 114 cases, six (5.3%) were identified as fibroblast growth factor receptor 2 fusions-positive with a high frequency (87% or more) of fibroblast growth factor receptor 2 fusions-positive tumour cells whereas the remainder, with the exception of three cases with indeterminate results, were identified as fibroblast growth factor receptor 2 fusions-negative. The patients' baseline characteristics as well as their objective response rates, disease control rates, times to progression, and times to treatment failure with previous or ongoing first-line chemotherapy did not have any obvious relationship to the proportion of fibroblast growth factor receptor 2 fusions-positive case. CONCLUSIONS: Further detailed elucidation of fibroblast growth factor receptor 2 fusion status is expected to contribute to the development of promising therapeutic options for patients suffering from recurrent or unresectable intrahepatic cholangiocarcinoma.

Randomised phase II trial of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab as first-line treatment for colorectal liver metastasis (ATOM trial).

BACKGROUND: Chemotherapy with biologics followed by liver surgery improves the resection rate and survival of patients with colorectal liver metastasis (CRLM). However, no prospective study has compared the outcomes of chemotherapy with bevacizumab (BEV) versus cetuximab (CET). METHODS: The ATOM study is the first randomised trial comparing BEV and CET for initially unresectable CRLM. Patients were randomly assigned in a 1:1 ratio to receive mFOLFOX6 plus either BEV or CET. The primary endpoint was progression-free survival (PFS). RESULTS: Between May 2013 and April 2016, 122 patients were enrolled. Median PFS was 11.5 months (95% CI 9.2-13.3 months) in the BEV group and 14.8 months (95% CI 9.7-17.3 months) in the CET group (hazard ratio 0.803; P = 0.33). Patients with a smaller-number but larger-sized metastases did better in the CET group. In the BEV and CET groups, the response rates were 68.4% and 84.7% and the resection rates were 56.1% and 49.2%, respectively. CONCLUSION: Although CET achieved a better response rate than BEV for patients with a small number of large liver metastases, both biologics had similar efficacy regarding liver resection and acceptable safety profiles. To achieve optimal PFS, biologics should be selected in accordance with patient conditions. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (number NCT01836653), and UMIN Clinical Trials Registry (UMIN-CTR number UMIN000010209).

Influence of age on postoperative complications especially pneumonia after gastrectomy for gastric cancer.

BACKGROUND: The aim of this study was to investigate the influence of patients' age on postoperative morbidities including pneumonia. METHODS: We reviewed the clinical records of 211 patients with stages I - III gastric cancer undergoing curative distal gastrectomy (DG) or total gastrectomy (TG). Patients were classified into an elderly (≧80 y.o.) or a control (< 80 y.o.) group. We compared patient characteristics (sex ratio, disease stage, degree of lymph node dissection, number of retrieved lymph nodes, and type of reconstruction) and early postoperative outcomes (operation time, intra-operative blood loss, and postoperative morbidity including pneumonia, and mortality) between the two groups separately in DG and TG. RESULTS: There were 134 and 77 patients who underwent DG and TG, respectively. The numbers of patients in the elderly and control groups were 25 and 109 in DG and 12 and 65 in TG. The percentage of female patients in the elderly group was greater than that in the control group in both DG and TG. The extent of lymph node dissection did not differ between two groups in TG; in contrast in DG, the rate of a D1 dissection was greater in the elderly group than in the control group. There were no differences between the two groups in distribution of disease stage, number of retrieved lymph nodes, operation time, and blood loss in DG and in TG. Overall postoperative morbidity did not differ between two groups after DG and after TG. The rate of infectious complications in the elderly group was not different from that in the control group after DG and after TG. The incidence of pneumonia was more frequent in the elderly group compared to the control group after DG (8% vs. 1%, P < 0.05) but not after TG (17% vs. 5%). When patients were compared between the elderly and the control groups regardless of type of gastrectomy, the incidence of pneumonia in the elderly group (4/37 (11%)) was greater than that in the control group (4/174 (2%), P < 0.05). CONCLUSIONS: These results suggest that pneumonia is increased in patients older than 80 years after DG.

Strategy of laparoscopic surgery for colon cancer of the splenic flexure: a novel approach.

BACKGROUND: The splenic flexure (SF) anatomy is complex due to multiple vessels, surrounding organs, layers, and irregular adhesions [1-3]. METHODS: Our laparoscopic approach involves a lateral-to-medial approach to the left-sided transverse mesocolon (TM), a medial-to-lateral approach to the left mesocolon (LM), and take-down of the remnant SF. First, the omental bursa is opened and its posterior wall and the anterior layer of the TM are dissected along the pancreas, where a gauze is placed. The TM is spread cephalad. A window in the TM is opened in the gauze seen through the TM. If necessary, the middle colic vessels are divided with lymph node (LN) dissection. Then the left colic artery is divided with LN dissection using a medial approach. The LM is widely dissected from the retroperitoneum to reach the TM window. While observing the pancreas through the window, the LM and TM are divided from the pancreas close to the SF. The descending colon is mobilized from its lateral attachment. Finally, the SF is taken down from the spleen by separating remnant structures, including adhesions. Subsequently, functional end-to-end anastomosis was performed extracorporeally. RESULTS: During March 2012-December 2016, 39 patients with left-sided transverse or descending colon cancer underwent this treatment. The mean operative time, blood loss, number of harvested LNs, and hospital stay duration were 283 min, 45 ml, 15, and 9 days, respectively. No patient needed conversion to open surgery or had organ injury, anastomotic leakage, or Clavien-Dindo III-V complications. There were 7/13/18/1 patients with Stage I/II/III/IV colon cancer, respectively. Nineteen cases had positive LNs. All patients were alive with one local and two distant recurrences at a mean 24-month follow-up. CONCLUSIONS: This is a safe and effective surgical strategy for treating colon cancer of the SF, strategically designed to resect the SF after dissecting the surrounding structures.

Tumescent TAPP: laparoscopic inguinal hernia repair after the preperitoneal tumescent injection of diluted lidocaine and epinephrine saline solution and carbon dioxide gas.

PURPOSE: Laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP) is technically difficult and not infrequently followed by postoperative complications and pain, especially when performed by inexperienced surgeons. To simplify TAPP and reduce postoperative pain, we devised a novel procedure whereby TAPP is carried out after the inguinal preperitoneal infiltration of diluted lidocaine and epinephrine saline solution and carbon dioxide gas (tumescent TAPP). This report introduces the concept of tumescent TAPP and summarizes its operative results. METHODS: About 120 ml of diluted lidocaine and epinephrine solution and 60 ml of CO2 gas were infiltrated into the inguinal preperitoneal space through a transabdominal needle before TAPP. Tumescent TAPP was performed for 400 patients (355 men, 45 women; mean age, 63.2 years). RESULTS: Using tumescent TAPP, we found it easier to confirm the inguinal anatomy and dissect the preperitoneal layer and inguinal floor, with less bleeding. The mean operation time was 101.9 min and there were few perioperative complications and minimal pain. CONCLUSIONS: Tumescent TAPP makes conventional TAPP easier and safer; however, this procedure should be verified by a comparative study with conventional TAPP.

Effect of Hospital Volume on Surgical Outcomes After Pancreaticoduodenectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the relationship between hospital volume and outcome after pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: Previous reviews for the hospital volume-outcome relationship after pancreatic resection were limited owing to clinical or methodological heterogeneity, resulting from differences in surgical procedures and high-volume hospital (HVH) definitions across studies. METHODS: We conducted a rigorous meta-analysis on the influence of hospital volume on various outcomes after PD using strict inclusion criteria and single cutoff values for HVHs. RESULTS: Thirteen studies based on nationwide databases from 11 countries, and including 58,023 patients in total, were included in this study. The overall pooled odds ratio (OR) for mortality favoring the HVH group was 2.37 [95% confidence interval (CI): 1.95-2.88] with high heterogeneity (I = 63%). We therefore classified all included studies into categories according to the cutoff values for HVH as defined in each individual study. The pooled OR for each category of 1 to 19, 20 to 29, and ≥30 PDs per year was 1.94, 2.34, and 4.05, respectively. There were significant differences among these categories (I = 58.9%, P = 0.09). The 2 former categories showed no statistical interstudy heterogeneities. The data did not suggest publication bias. These trends persisted in all subgroup analyses. Postoperative length of stay in the HVH group was significantly shorter with mild interstudy heterogeneity. CONCLUSIONS: This meta-analysis included studies from different countries with disparate health care systems and provided strong evidence for an inverse association between higher hospital volume and lower mortality after PD. Variations in HVH cutoff values across studies majorly influenced the overall heterogeneity.

Aberrant activation of Notch signaling in extrahepatic cholangiocarcinoma: clinicopathological features and therapeutic potential for cancer stem cell-like properties.

BACKGROUND: Little is known about the roles of Notch signaling in cholangiocarcinoma (CC). The expression of hairy and enhancer of split 1 (Hes-1) has not been investigated yet in resected specimens of CC. Notch signaling has been reported to be related to cancer stem cell (CSC) like properties in some malignancies. Our aim is to investigate the participation of Notch signaling in resected specimens of extrahepatic CC (EHCC) and to evaluate the efficacy of CC cells with CSC-like properties by Notch signaling blockade. METHODS: First, the expression of Notch1, 2, 3, 4 and Hes-1 was examined by immunohistochemistry in 132 resected EHCC specimens. The clinicopathological characteristics in the expression of Notch receptors and Hes-1 were investigated. Second, GSI IX, which is a γ-secretase-inhibitor, was used for Notch signaling blockade in the following experiment. Alterations of the subpopulation of CD24+CD44+ cells, which are surface markers of CSCs in EHCC, after exposure with GSI IX, gemcitabine (GEM), and the combination of GSI IX plus GEM were assessed by flow cytometry using the human CC cell lines, RBE, HuCCT1 and TFK-1. Also, anchorage-independent growth and mice tumorigenicity in the cells recovered by regular culture media after GSI IX exposure were assessed. RESULTS: Notch1, 2, 3, 4 and Hes-1 in the resected EHCC specimens were expressed in 50.0, 56.1, 42.4, 6.1, and 81.8 % of the total cohort, respectively. Notch1 and 3 expressions were associated with poorer histological differentiation (P = 0.008 and 0.053). The patients with the expression of at least any one of Notch1-3 receptors, who were in 80.3 % of the total, exhibited poorer survival (P = 0.050). Similarly, the expression of Hes-1 tended to show poor survival (P = 0.093). In all of the examined CC cell lines, GSI IX treatment significantly diminished the subpopulation of CD24+CD44+ cells. Although GEM monotherapy relatively increased the subpopulation of CD24+CD44+ cells in all lines, GSI IX plus GEM attenuated it. Anchorage-independent growth and mice tumorigenicity were inhibited in GSI IX-pretreated cells in RBE and TFK-1 (P < 0.05). CONCLUSION: Aberrant Notch signaling is involved with EHCC. Inhibition of Notch signaling is a novel therapeutic strategy for targeting cells with CSC-like properties.

Telomerase activity in pancreatic juice differentiates pancreatic cancer from chronic pancreatitis: A meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the usefulness of genetic markers in pancreatic juice (PJ), and the combination of these markers with telomerase activity in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis. METHODS: We conducted a meta-analysis for the diagnostic utility of the four major altered genes in PDAC (KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4), telomerase activity, and a combination assay using PJ samples. A literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. Data were pooled and presented as diagnostic sensitivity and specificity with 95% confidence intervals (CIs). RESULTS: Thirty-nine studies fulfilled the inclusion criteria. Pooled estimates of KRAS analysis were as follows: sensitivity was 0.67 (95% CI, 0.63-0.71) and specificity, 0.82 (95% CI, 0.79-0.85). For telomerase activity analysis, sensitivity was 0.82 (95% CI, 0.76-0.87) and specificity, 0.96 (95% CI, 0.90-0.99). The other three tumor suppressors demonstrated low sensitivity. The data did not suggest any publication bias. A combined analysis of KRAS and telomerase activity showed a higher diagnostic sensitivity (0.94; 95% CI, 0.83-0.99) than KRAS alone. A combined analysis of telomerase activity and cytology revealed more reliable diagnostic accuracy than telomerase activity alone, with high sensitivity (0.88; 95% CI, 0.74-0.96) and specificity (1.00; 95% CI, 0.91-1.00). CONCLUSIONS: The most reliable marker in PJ samples for diagnosis of PDAC was telomerase activity. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and can increase diagnostic accuracy when combined with KRAS mutations or cytological examination.

Risk factors for recurrent biliary obstruction following placement of self-expandable metallic stents in patients with malignant perihilar biliary stricture.

BACKGROUND AND STUDY AIM: Self-expandable metallic stents (SEMSs) are used for palliation in patients with malignant perihilar biliary strictures. However, recurrent biliary obstruction occasionally causes cholangitis and jaundice. This study aimed to identify risk factors for recurrent biliary obstruction in such patients. METHODS: Data from consecutive patients with malignant perihilar biliary strictures treated with endoscopic placement of SEMSs between 2007 and 2014 in Tohoku University Hospital were retrospectively reviewed. Risk factors for recurrent biliary obstruction were calculated using the Cox proportional hazards models (with hazard ratios [HRs] and 95 % confidence interval [95 %CIs]), and SEMS patency period was examined using the Kaplan - Meier method. SEMS patency was defined as the period between SEMS insertion and the development of recurrent biliary obstruction. RESULTS: 104 patients were included. Median survival time was 281 days; and 85 patients died during a median follow-up period of 320 days. Recurrent biliary obstruction occurred in 35 patients. Median SEMS patency period was 549 days. Multivariable analyses showed that: compared with bile duct carcinoma, gallbladder carcinoma was associated with shorter SEMS patency (HR 8.18, 95 %CI 2.41 - 26.83); patency of left-sided SEMS was inferior to that of bilateral (HR 0.5, 95 %CI 0.32 - 0.93) and right-sided SEMS (HR 0.1, 95 %CI 0.02 - 0.65). Cholangitis before SEMS placement increased the risk of recurrent biliary obstruction (HR 11.44; 95 %CI 4.48 - 32.35) and reduced the SEMS patency period (746 vs. 210 days). CONCLUSION: Gallbladder carcinoma, left-sided stent placement, and cholangitis before SEMS placement are risk factors for recurrent biliary obstruction after SEMS placement.

Bismuth classification is associated with the requirement for multiple biliary drainage in preoperative patients with malignant perihilar biliary stricture.

BACKGROUND: Single preoperative biliary drainage for malignant perihilar biliary stricture occasionally fails to control jaundice and cholangitis. Multiple biliary drainage is required in such cases, but their clinical background is unclear. We determined the clinical characteristics associated with the requirement for multiple biliary drainage. METHODS: The consecutive 122 patients with malignant perihilar biliary stricture were enrolled in a single-center retrospective study. Preoperative biliary drainage was initially performed on the future remnant hepatic lobe. Additional drainage was performed if jaundice failed to improve or cholangitis developed in undrained hepatic lobes. Detailed clinical characteristics and the number of preoperative biliary drainage procedures required before operation were analyzed. RESULTS: Thirty-one patients (25.4%) initially underwent multiple biliary drainage. However, 69 (56.7%) required multiple biliary drainage by the time of the operation. In the univariate analysis, the initial serum bilirubin level, cholangitis, percutaneous portal vein embolization, history of inserted endoscopic biliary stenting, length of preoperative period, operative procedure, and Bismuth classification were significant factors. In the multivariate analysis using these factors, Bismuth classification was independently associated with the requirement for multiple biliary drainage. The number of patients who required multiple biliary drainage was higher in those with Bismuth-II (91.9%), Bismuth-IIIa (65.7%), and Bismuth-IV (92.9%) than in those with Bismuth-I (22.2%) and Bismuth-IIIb (18.2%). CONCLUSIONS: Patients with Bismuth-II, Bismuth-IIIa, and Bismuth-IV are at higher risk for multiple biliary drainage. A strategy based on the Bismuth classification for performing preoperative biliary drainage is important for patients with malignant perihilar biliary stricture.

Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).

BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer. METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS). RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases. CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.

Long-term outcomes after extrahepatic excision of congenital choladocal cysts: 30 years of experience at a single center.

BACKGROUND/AIMS: Congenital choladocal cysts are generally treated by resection of the dilated extrahepatic biliary duct followed by hepaticojejunostomy, but it is associated with postoperative complications, including postoperative cholangitis, intrahepatic calculi, pancreatitis, and carcinogenesis, in the remnant bile duct. We investigated the most common long-term complications and identified the factors implicated in their development. METHODOLOGY: We conducted a retrospective review and analysis of the long-term complications of 65 patients surgically treated for congenital choledochal cysts between 1978 and 2008 at one institute. The risk factors for intrahepatic calculi were identified based on the odds ratios of the implicated variables. RESULTS: Cholangitis with high fever or abdominal pain was reported in 14 patients (21.5%), intrahepatic calculi in 12 (18.5%), pancreatitis in 3 (4.6%), and cholangiocarcinoma in 3 (4.6%). Diagnosis with type IVa choledochal cysts was the most significant risk factor, followed by age ≥30 years at the time of treatment, and the presence of preoperative intrahepatic calculi. CONCLUSIONS: While precise and thorough surgical treatment is necessary to prevent the long-term development of complications after surgical excision of congenital choledochal cysts, it must be accompanied by long-term postoperative follow-up, especially of elderly patients and those with type IVa cysts.

Clinicopathological features and surgical outcomes of adenosquamous carcinoma of the pancreas: a retrospective analysis of patients with resectable stage tumors.

PURPOSE: Adenosquamous carcinoma of the pancreas is a rare subtype of pancreatic cancer. We herein describe the clinicopathological features of surgically resected cases of adenosquamous carcinoma of the pancreas. METHODS: From 2001 to 2011, 132 patients underwent R0 resection for Stage IIA or IIB pancreatic cancer. The survival rate, pathological features and recurrence status were reviewed. RESULTS: Out of 132 patients, 121 patients had tubular adenocarcinoma, and only seven had adenosquamous carcinoma (ASC). The incidence of ASC increased with the tumor size. The overall survival and disease-free survival periods of the patients with ASC were significantly shorter than those of patients with tubular adenocarcinoma (p = 0.0153 and p = 0.0045). The histological findings revealed more marked venous invasion in ASC compared to tubular adenocarcinoma (G1, G2 and G3). The proportion of v3 cases, which denotes the most severe venous invasion, was 31.3 % in G1, 47.3 % in G2, 60.0 % in G3 and 71.4 % in ASC cases, respectively. Other factors, including lymphatic and nerve invasion, were not correlated with the histological subtypes. The incidence of ASC was 11.1 % in the tumors more than 6 cm in diameter, and 0 % in those less than 2 cm in diameter. CONCLUSIONS: We revealed that adenosquamous carcinoma of the pancreas is associated with a poor outcome, and also clarified its clinicopathological features.

[Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy].

A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma.