The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.

Surgical tips and tricks for laparoscopic intragastric surgery for submucosal tumors relative to the esophagogastric junction.

Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ.

Efficacy of palliative surgery for gastric cancer patients with peritoneal metastasis who still have residual peritoneal dissemination after chemotherapy.

PURPOSE: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy. METHODS: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared. RESULTS: In the PS group, total and distal gastrectomies were performed. Clavien-Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044). CONCLUSIONS: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy.

Impact of tumor-related factors and inter-institutional heterogeneity on preoperative T staging for gastric cancer.

Background: To improve the diagnostic accuracy of preoperative T staging in gastric cancer, the authors evaluated tumor-related factors that might affect the diagnosis. Materials & methods: The authors analyzed the data of cT2-4b gastric cancer patients enrolled in the prospective, multicenter JCOG1302A study. They used contrast-enhanced computed tomography to analyze the association between tumor-related factors and the diagnostic accuracy of T3-4b staging for gastric cancer. Results: Among 876 cT3-4b tumors, the diagnostic accuracy was relatively low in the lower third of the stomach compared with those in the upper or middle. A multivariable analysis revealed that accuracy was higher in the lesser curvature or entire circumference region than in other areas (p < 0.001), in macroscopic types 3/5 than in types 0/1/2 (p = 0.003) and in the undifferentiated histological type than in the differentiated type (p = 0.011). Conclusion: The authors found tumor-related factors affecting preoperative T staging by enhanced computed tomography.

Additional chemotherapy before surgery is expected to have potentially beneficial effects on prognosis compared with chemotherapy only after surgery for advanced gastric cancer. The consideration of chemotherapy before surgery depends on preoperative diagnosis of the depth of tumor invasion in the stomach wall. Overdiagnosis of the depth of tumor invasion may lead to unnecessary administration of chemotherapy that is harmful to the patient. Tumor-related factors such as tumor location, macroscopic type and histological type may affect the diagnosis. Therefore, these factors should be considered with special care for the diagnosis, which may lead to higher accuracy in diagnosing the depth of tumor invasion in gastric cancer.

Usefulness of microfocus computed tomography in life science research: preliminary study using murine micro-hepatic tumor models.

PURPOSE: Microfocus computed tomography (micro-CT) has not been widely used at high radiation intensity (industrial micro-CT) in life science fields. In this preliminary study, we investigated its potential value in the detection of micro-hepatic tumors in a mouse model. METHODS: The liver with micro-hepatic tumors was surgically resected en-bloc from mice, and examined with industrial micro-CT and lower intensity micro-CT (small animal micro-CT). The number of hepatic tumors was manually counted on serial images. Then, the accuracy of each technique was determined by preparing matching liver sections and comparing the number of tumors identified in a conventional pathological examination. RESULTS: The number of hepatic tumors evaluated with industrial micro-CT showed high concordance with the results of the pathological examinations (intraclass correlation coefficient [ICC]: 0.984; 95% confidence interval [CI] 0.959-0.994). On the other hand, the number of hepatic tumors evaluated with the small animal micro-CT showed low concordance with the number identified in the pathological examinations (ICC: 0.533; 95% CI 0.181-0.815). CONCLUSION: Industrial micro-CT improved the detection of small structures in resected specimens, and might be a promising solution for life science research.

Pathological Regression of Lymph Nodes Better Predicts Long-term Survival in Esophageal Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery.

OBJECTIVE: To evaluate pathological response to NAC in metastatic LNs, and assess its clinical prognostic significance in patients with EC. SUMMARY OF BACKGROUND DATA: The pathological response to preoperative treatment is commonly evaluated in the PT. However, LN metastases strongly correlate with systemic micro-metastases. Thus, pathological evaluation of LN response could more accurately predict prognosis in EC patients undergoing NAC before surgery. METHODS: We enrolled 371 consecutive patients who underwent triplet NAC followed by surgery for EC between January 2010 and December 2016. Pathological LN regression grade was defined by the proportion of viable tumor area within the whole tumor bed area for all metastatic LNs: grade I, >50%; II, 10%-50%; III, <10%; and IV, 0%. We analyzed the correlation of grade with clinico-pathological parameters. RESULTS: Among 319 patients with clinically positive LNs, pathological LN regression grades were I/II/III/IV in 115/51/58/95 patients, and 191 patients (59.9%) showed discordance between the PT and LN pathological regression grades. LN regression grade significantly correlated with cN positive number, ypTNM, lymphovascular invasion, and clinical/pathological PT response. Multivariate analysis for recurrence-free survival revealed that LN regression grade [hazard ratio (HR) = 2.25, P < 0.001], ypT (HR = 1.65, P = 0.005), and ypT (HR = 1.62, P = 0.004) were independent prognostic factors, but not pathological PT regression grade (P = 0.67). CONCLUSIONS: Compared to PT response, pathological LN response better predicted long-term survival in EC patients who received NAC plus curative surgery.

Anti-metastatic effect of methylprednisolone targeting vascular endothelial cells under surgical stress.

Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.

Taste alteration after gastrectomy in patients with gastric cancer.

PURPOSE: To investigate the relationship between changes in taste due to surgical procedures and other clinical factors, we performed a detailed investigation of taste alteration in patients who underwent gastrectomy. METHODS: Questionnaires on taste alteration were distributed to patients who visited our outpatient clinic from July 2018 to January 2019 for the postoperative evaluation of gastric cancer. Associations of clinical characteristics with changes in sensitivity to the four major taste types (sweet, sour, salty, and bitter) were examined. RESULTS: Of the 243 eligible patients, 42 (17.3%) experienced taste alteration after gastrectomy; taste sensitivity decreased in 21 (8.6%) patients and increased in 31 (12.7%) patients. The frequency of a decreased sensitivity to sweet was significantly higher in patients who underwent total gastrectomy than in those who underwent distal gastrectomy (18.8% vs. 3.3%, P = 0.001). Patients who underwent total gastrectomy were significantly more likely than those who received distal gastrectomy to experience increased sensitivity to sour (12.5% vs. 2.2%, respectively; P = 0.004) and bitter (15.6% vs. 3.8%, respectively; P = 0.007) tastes. A multivariate analysis revealed that total gastrectomy was an independent risk factor for total taste alteration. CONCLUSIONS: Patients who underwent total gastrectomy showed a high likelihood of both loss and gain of taste sensitivity.

Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer.

BACKGROUND: Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. METHODS: In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. RESULTS: Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0-1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2-3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001). CONCLUSIONS: PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. CLINICAL TRIAL REGISTRATION: UMIN000032164.

Molecular Barcode Sequencing for Highly Sensitive Detection of Circulating Tumor DNA in Patients with Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Next-generation sequencing (NGS) with molecular barcodes (MB) is a novel method that enables the highly sensitive detection of circulating tumor DNA (ctDNA) in a relatively wide range of genes. OBJECTIVE: The aim of this study was to examine the utility of NGS with MB for detecting ctDNA in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Five patients with ESCC who underwent preoperative treatment followed by esophagectomy were examined. The frequency of TP53 mutations in DNA extracted from tumor tissue and plasma at each time point during the treatment course was analyzed using NGS without MB. In 1 patient, additional analysis using NGS with MB was conducted to compare the sensitivities and to evaluate the clinical utility of this novel method. RESULTS: TP53 mutations in tumor tissue were identified in 3 of 5 patients with ESCC. In 1 patient, the mutational allele frequency in plasma was 1.97% before preoperative treatment, and decreased to 0.09% after preoperative treatment. As the maximum frequency of background errors were 3.22% using NGS without MB and 0.08% with MB, which indicated that the sensitivity of ctDNA detection using NGS with MB was much higher than without MB. In 1 patient who had recurrence half a year after surgery, only NGS with MB could detect ctDNA even at 4 weeks after surgery, at a frequency of 0.20%. CONCLUSIONS: NGS with MB enabled comprehensive and highly sensitive detection of ctDNA in a patient with ESCC. This novel method may be useful for the clinical diagnosis of ESCC.

Dysphagia Score as a Predictor of Adverse Events Due to Triplet Chemotherapy and Oncological Outcomes in 434 Consecutive Patients with Esophageal Cancer.

BACKGROUND: Dysphagia is a major symptom of esophageal cancer (EC) that significantly affects patient quality of life; however, little is known regarding its clinical impact on the treatment course in patients with EC. METHODS: This retrospective study included 434 consecutive patients with EC who received docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy as an initial treatment. We evaluated the relationships between the dysphagia score at diagnosis and clinicopathological factors, including DCF therapy-related adverse events, tumor response, and survival. RESULTS: The dysphagia scores were 0 in 208 patients (47.9%), 1 in 82 patients (18.9%), 2 in 52 patients (12.0%), 3 in 59 patients (13.6%), and 4 in 33 patients (7.6%). High (≥ 3) dysphagia scores were significantly associated with high incidences of grade 3/4 febrile neutropenia (FN) (79.3 vs. 35.7%, P < 0.001) and diarrhea (63.0 vs. 28.1%, P < 0.001) compared with low (≤ 2) scores. Logistic regression analysis further identified the dysphagia scores as an independent predictor of both FN and severe diarrhea during DCF chemotherapy. Furthermore, compared with low scores, high dysphagia scores were associated with a worse clinical response to chemotherapy (response rate 65.2 vs. 78.7%, P = 0.008) and worse 5-year overall survival (35.4 vs. 56.4%, P = 0.001). CONCLUSIONS: The dysphagia score at diagnosis was an independent predictor of FN and severe diarrhea. Furthermore, this score might be useful in predicting chemotherapy response and long-term survival in patients treated with DCF.

Methylprednisolone Inhibits Tumor Growth and Peritoneal Seeding Induced by Surgical Stress and Postoperative Complications.

BACKGROUND: Surgery often introduce inflammatory response, which may promote tumor growth and metastasis of residual cancer cells. We investigated the impacts of methylprednisolone on the tumor growth and peritoneal seedings in mice treated with lipopolysaccharide (LPS), which mimics systemic inflammation induced by surgical stress and postoperative complications. METHODS: The serum interleukin-6 (IL-6) levels, tumor volume, tumor weight, and the number of peritoneal nodules were investigated in tumor growth model and peritoneal seeding model using BALB/c mice and murine CT26 cancer cell lines in vivo. We conducted functional analyses of IL-6 in Western blotting and proliferation assays in vitro. We also investigated whether preoperative administration of methylprednisolone decreased postoperative serum IL-6 levels in cancer patients in a randomized clinical study. RESULTS: In the in vivo study, methylprednisolone inhibited the LPS-induced increase of serum IL-6 levels (mean, 33,756 pg/ml vs. 5917 pg/ml; P < 0.001), tumor volume (mean, 397 mm3 vs. 274 mm3; P = 0.019), tumor weight (mean, 0.38 g vs. 0.15 g; P = 0.020), and the number of peritoneal nodules (mean, 112 vs. 47; P = 0.002). In the in vitro study, IL-6 enhanced JAK/STAT signaling and increased the cell proliferation, and IL-6R-neutralizing antibody attenuated these effects. In the clinical study, serum IL-6 levels were significantly decreased by methylprednisolone (median, 97.5 pg/ml vs. 18.0 pg/ml; P = 0.030). CONCLUSIONS: Surgical stress and postoperative complications may enhance tumor growth due to the increase of IL-6. However, methylprednisolone can decrease serum IL-6 levels, thus inhibiting tumor growth and peritoneal seeding.

A primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular Brunner's glands.

BACKGROUND: Primary hepatic gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular Brunner's glands in a patient who instead, preoperatively, was suspected of having multiple duodenal gastrinomas and hepatic metastasis. CASE PRESENTATION: A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a gastrinoma, and there was no gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a gastrinoma in the liver, but no gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner's glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. CONCLUSION: We report a case of primary hepatic gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner's glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia.

A mesenteric solid tumor with unusual features in a young male: A case report.

The current study presents a mesenteric mesenchymal tumor case, with unusual features in diagnostic imaging and histology. A 16-year-old male was admitted to the hospital with abdominal pain. Computed tomography (CT) revealed an abdominal mass, 2 cm in diameter. The results of contrast-enhanced CT, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography indicated no specific features suggestive of its histology. Two arteries branching from the superior mesenteric artery were observed feeding the hypervascular tumor. After endoscopic and other laboratory findings revealed no additional lesions, the lesion was diagnosed as a primary mesenteric tumor. As the possibility of malignancy and future bleeding from this tumor could not be ruled out, a resection of the tumor was performed. During the surgery, the tumor, which was well circumscribed and hypervascular, was located in the mesentery of the jejunum. The resected tumor did not exhibit typical histological characteristics, and was labeled as 'myxoid smooth muscle neoplasm of uncertain biologic potential'. At 2 years after surgery, the patient remained well without evidence of recurrence. As primary mesenteric tumors are rare, particularly in young patients, it is considered important that this type of unusual tumor be included in the differential diagnosis for mesenteric tumors.

Case of ileal herniation through the foramen of Winslow diagnosed preoperatively by CT and treated with laparoscopic surgery.

A previously healthy 35-year-old man visited the emergency room complaining of epigastric pain and vomiting. The pain was sudden in onset. His blood tests were within normal limits except for a mild neutrophilia of 14 300/µL. Enhanced abdominal CT scan showed the small intestine dilated into the space between the portal vein and inferior vena cava from the foramen of Winslow. Under the diagnosis of herniation through the foramen of Winslow (HFW), we performed emergency laparoscopic surgery. Laparoscopy revealed an internal herniation of the dilated small intestine through the foramen of Winslow. Because the herniated small intestine was viable, intestinal resection was unnecessary. We released the incarceration under laparoscopy. HFW is very rare and often overlooked, but abdominal CT examination enabled a precise preoperative diagnosis because of characteristic findings. We should consider the possibility of HFW in patients with internal herniation of unknown origin. Laparoscopic surgery for HFW is effective.

[A case of extragastrointestinal stromal tumor with peritoneal dissemination].

Here, we present the case of a 60-year-old man in whom abdominal computed tomography showed a solid abdominal tumor (11 cm in diameter) in the pelvic space, with widely disseminated nodular lesions. Emergency surgery was performed following the rapid onset of intense abdominal pain. Peritoneal disseminations were widespread and the tumor was confirmed to be in the pelvic space. The tumor was not connected to any segment of the intestinal tract but rather to the retroperitoneum. Immunohistochemical staining was positive for c-kit (exon 11 mutation) and CD34 but negative for S-100 protein. Careful postoperative examination did not reveal any lesions in the upper or lower alimentary tract. On the basis of these findings we diagnosed the tumor as an extragastrointestinal stromal tumor (EGIST) originating from the retroperitoneum. After surgery, intravenous infusion of imatinib was started at a full dose of 400mg/day; however, owing to strong adverse effects, the dose was reduced to 200mg/day. Despite halving the dose, the patient has remained lesion-free according to computed tomography for 36 months after the operation. Low-dose imatinib chemotherapy remained efficacious in controlling progression in this case.

[A case of synchronous cancer of the gall bladder, common bile duct, and the papilla of vater].

A 58-year-old man was diagnosed with liver dysfunction during a health exam and subsequently visited a doctor. Abdominal ultrasonography revealed space-occupying lesions in the gall bladder and bile duct, and he was hospitalized for further examination and treatment. Computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiopancreatography (MRCP) revealed double cancer of the gall bladder and bile duct with pancreaticobiliary maljunction (PBM), and we performed a pancreatoduodenectomy. Pathological examination revealed gall bladder and bile duct cancer, and severe dysplasia of the papilla of Vater. We diagnosed synchronous triple cancer because none of the cancers had continuity or vascular invasion. Each cancer was at Stage I, and the patient has survived for 2 years and 6 months without recurrence and no additional treatment. PBM is a mutation of the junction of the pancreatic and bile ducts outside of the duodenal wall, and is a known complication of biliary tract cancer due to the reflux of pancreatic juice and bile. Because K-ras and p53 gene mutations occur in the biliary tract mucosal epithelium, PBM increases the risk of developing multicentric cancer. It is important to consider the existence of double cancer when biliary tract cancer is detected in a PBM patient.

[A case of postpancreaticoduodenectomy local recurrence successfully treated with extended resection].

A 68 -year-old man underwent a pancreaticoduodenectomy after being diagnosed with primary duodenal cancer. The postoperative pathological diagnosis was tub2, SE, ly1, v1, panc3, pn+, N0. Although adjuvant chemotherapy was administered, local recurrence in the portal region was detected 18 months later. The recurrent tumor pressed against the region of the bile duct anastomosis, which caused obstructive jaundice. After serum bilirubin levels were reduced, resection of the recurrent tumors was performed. This required resection of the transverse colon, parts of the portal vein, and the inferior vena cava. The bile duct anastomotic region, which had been infiltrated by the tumor, was excised and rebuilt. The postoperative pathological diagnosis was tub2. The patient continued to receive adjuvant chemotherapy and showed no signs of recurrence 9 months after surgery. Extended resection for local recurrences of primary duodenal cancer may be an effective means of disease control.