Cancer-related genetic variants of Helicobacter pylori strains determined using gastric wash-based whole-genome analysis with single-molecule real-time technology.

Helicobacter pylori (H. pylori) are a primary factor in the pathogenesis of gastric cancer (GC); GC ranks third among cancer-related mortality. A clear understanding of the H. pylori genome factors underlying GC is necessary to develop more effective methods to prevent GC. A single-molecule real-time DNA sequencing-based H. pylori genome-wide association study analysis was performed using the H. pylori genome present in five early-stage GC (EGC) and five non-GC clinical DNA samples recovered from gastric washes. A total of 275 genes with 702 nucleotide variants (NVs) were found to be common to three or more patients with EGC but no non-GC patients (single-NV: 654/702, 93.2%; multi-NV: 40/702, 5.7%; deletion: 3/702, 0.4%; insertion: 3/702, 0.7%). Gene ontology analysis of H. pylori revealed that genes involved in the mitochondrial electron transport system, glycolytic processes and the TCA cycle were highly enriched. Cancer-related NVs were most frequently found in a member of the Helicobacter outer membrane protein family, hopL. In particular, one of the NVs in hopL was a novel six-nucleotide insertion (1159095̂1159096, TACTTC); this mutant was detected more frequently in a validation set of 50 additional EGC samples (22/50, 44.0%) than in 18 non-GC samples (3/18, 16.7%, P = .04). These results suggest that the hopL variant is associated with the development of GC and may serve as a genetic biomarker of H. pylori virulence and GC risk. Our assay can serve as a potent tool to expand our understanding of bacteria-associated tumorigenesis.

Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report.

The CyberKnife® is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post-vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment.

Evaluation of predictive factors in patients with nonalcoholic fatty liver disease after pancreaticoduodenectomy.

Patients who undergo pancreaticoduodenectomy (PD) are at risk of steatosis because resection of the pancreatic head causes pancreatic exocrine and endocrine insufficiency. We investigated the clinicopathological features and the risk factors of nonalcoholic fatty liver disease (NAFLD) after PD. This was a retrospective study of 100 patients who underwent PD between April 2007 and December 2012 in our institution. Preoperative demographic and clinical data, surgical procedures, pathological diagnosis, postoperative course findings, and complication details were collected prospectively. The patients were divided into the following two groups: Group A consisted of 12 patients who developed postoperative NAFLD, and Group B consisted of 88 patients who did not develop postoperative NAFLD. Pancreatic carcinoma and pancreatic texture showed similar findings. Additionally, we found that blood loss significantly correlated with the incidence of nonalcoholic steatohepatitis after PD. In multivariate analysis, only blood loss was identified as the most influential risk factor for NAFLD (hazard ratio, 1.0001; P = 0.016). Blood loss was identified as an independent risk factor for the development of NAFLD after PD. Further prospective studies are needed to identify factors that put patients at risk for NAFLD after PD. Continuing efforts should be made to improve patient outcomes and understand the pathogenesis of postpancreatectomy NASH.

Clinicopathological features of early distal cholangiocarcinoma.

BACKGROUND/AIM: The purpose of this study was to evaluate the clinicopathological features of early distal cholangiocarcinoma compared with advanced tumors. METHODOLOGY: This was a retrospective study of 45 patients who underwent resection for distal cholangiocarcinoma. There were 17 cases of early and 28 cases of advanced tumors. Data on demographic and clinical features, surgical procedures, and pathological diagnoses were collected retrospectively. RESULTS: Preoperative mean serum levels of bilirubin, alkaline phosphatase, and gamma-glutamyltransferase were statistically different between the early and advanced groups. There were no significant differences in the diameter of the common hepatic duct between groups, and there were significant differences in all tests but intraductal ultrasonography (IDUS) in tumor detection, meaning that IDUS is a very useful modality for detecting early and advanced cancer although early cancer is difficult to detect using other modalities. CONCLUSIONS: We believe that early cancer detection will generally lead to better prognosis. Further studies are needed, and efforts should continue to identify patients with suspicious findings.

[Efficacy and safety of cetuximab+irinotecan for unresectable advanced or recurrent colorectal cancer].

BACKGROUND: In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan. PURPOSE: We retrospectively analyzed the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region. PATIENTS AND METHODS: The number of patients enrolled was 38, all of whom were treated after second-line therapy. RESULTS: The RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days. CONCLUSION: At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy.

Diagnosis of distal cholangiocarcinoma after the removal of choledocholithiasis.

Background and Aim. Distal cholangiocarcinoma associated with choledocholithiasis has not been reported, and the causal relationship remains to be established. We evaluated diagnosis of distal cholangiocarcinoma diagnosed after the removal of choledocholithiasis. Patients and Methods. We assigned 9 cases of cholangiocarcinoma with choledocholithiasis to Group A. As a control group, 37 patients with cholangiocarcinoma without choledocholithiasis were assigned to Group B. Results. Abdominal pain at admission is the only significant difference between Group A and Group B (P = 0.001). All patients in Group A had gall bladder stones, compared with 7 patients (19%) in Group B (P < 0.01). Of the 9 patients in Group A, endoscopic retrade cholangiopancreatography (ERCP) detected normality in 2 patients (22%) and abnormalities in 7 patients (78%). Of the 32 patients in Group B, ERCP detected normality in 4 patients (13%) and abnormalities in 28 patients (88%) (P = 0.597). Intraductal ultrasonography (IDUS) detected a tumor in 8 patients in Group A, while in Group B, IDUS detected normality in 1 patient (3%) and tumors in 29 patients (97%) (P = 1.000). Conclusions. IDUS after stone removal may potentially help in the detection of unexpected tumors. Therefore, we believe that IDUS after stone removal will lead to improve outcome and prognosis.

Endoscopic management of pancreatic duct injury by endoscopic stent placement: a case report and literature review.

Recently, the diagnostic evaluation of pancreatic injury has improved dramatically. On the other hand, it is occasionally difficult to diagnose pancreatic injury, because there are no specific signs, symptoms, or laboratory findings. Radiological imaging also often fails to identify pancreatic injury in the acute phase. Delayed diagnosis results in significant morbidity and mortality. Most cases of pancreatic injury with suspicion or pancreatic duct disruption require surgery. Endoscopic retrograde cholangiopancreatography is one of the most accurate modalities for ductal evaluation and therapy and might enable one to avoid unnecessary surgery. We describe endoscopic management of pancreatic duct injury by endoscopic stent placement. A 45-year-old woman was admitted after a traffic accident. A computed tomography scan showed pancreatic parenchyma disruption at the pancreatic head. Endoscopic retrograde cholangiopancreatography demonstrated disruption of the pancreatic duct with extravasation into the peripancreatic fluid collection. A 5-French endoscopic nasopancreatic drainage (ENPD) tube was placed. Her symptoms dramatically improved. ENPD tube was exchanged for a 5-French 5-cm pancreatic stent. Subsequent follow-up CT revealed remarkable improvement. On the 26th day, the patient was discharged from the hospital without symptoms or complications. In this report, a pancreatic stent may lead to rapid clinical improvement and enable surgery to be avoided. On the other hand, the reported complications of long-term follow-up make the role of stenting uncertain. Thus, close attention should be paid to stenting management in the follow-up period. A pancreatic stent is useful for pancreatic ductal injury. If pancreatic ductal injury is managed appropriately, a pancreatic stent may improve the clinical condition, and also prevent unnecessary surgery.

Strategies to prevent pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND/AIMS: We evaluated the prevention of pancreatic fistula after pancreaticoduodenectomy in a retrospective clinical study. METHODOLOGY: Eighty patients undergoing pancreaticoduodenectomy between April 2007 and August 2011 were recruited.In all patients, the pancreas was reconstructed first,followed by reconstruction of the hepatic duct and the duodenum or stomach. RESULTS: Pancreatic fistulae were observed in 21 of 80 patients (26.3%; Grade A/B/C: 9/12/0). The incidence of pancreatic fistula in patients with soft pancreas was higher than that inpatients with hard pancreas (p<0.01). We investigated 54 patients with soft pancreas and pancreatic fistulae were diagnosed in 19 patients (35.2%; Grade A/B/C: 8/11/0). We evaluated pancreatic drainage methods (internal stent/external stent: 20/34) and in patients with soft pancreata, pancreatic fistulae were observed in 11 patients (55%) with internal stents vs. eight patients (23.5%) with external stents(p<0.05). CONCLUSIONS: We evaluated the management of pancreatic drainage methods and external stents were associated with a significantly lower incidence of pancreatic fistula compared with internal stents.We expect that external drainage of soft pancreas will decrease pancreatic juice leakage into the abdominal cavity. Many randomised control trials on pancreatic drainage have been reported recently; we plan to study them.

The impact of obesity on perioperative outcomes of pancreaticoduodenectomy.

BACKGROUND/AIMS: The purpose of this study was to evaluate the impact of obesity on pancreaticoduodenectomy (PD) outcomes. METHODOLOGY: Subjects were 97 patients undergoing PD at our institution between April 2005 and April 2011. All patients had data including body mass index (BMI). Patients were divided into two groups based on BMI; normal group (BMI <25kg/m2) and overweight group (BMI >25kg/m'). Perioperative outcomes were collected prospectively. RESULTS: There were no significant differences between the two groups in terms of intraoperative data, surgical time, blood loss and blood transfusion rates. The over-all complication rate was 50.0% (53.6% in the over- weight group and 47.1% in the normal group; p=0.55).The most common complication overall was pancreatic fistula (34.7%). There was also a significant difference in the rate of intra-abdominal fluid collection (four patients in the overweight group (14.3%) vs. two patients in the normal group (2.9%), respectively; p<0.05).There was no significant difference in the mortality rate between the normal group and the overweight group(3.6% vs. 0%, p=0.11). CONCLUSIONS: Management of overweight patients in the perioperative period should therefore address any modifiable risk factors for operative complications.

Clinicopathological feature of extrahepatic cholangiocarcinoma without jaundice: a single-center experience.

BACKGROUND/AIMS: The prognosis remains unsatisfactory even if the patient undergoes extensive surgery, which is the only curative treatment for these tumors. Therefore, early detection and diagnosis are needed to improve long-term survival. To investigate the clinicopathological feature of extrahepatic cholangiocarcinoma in patients presenting without jaundice compared with the features of tumors in patients presenting with jaundice. METHODOLOGY: This was a retrospective study of 50 patients resected for extrahepatic cholangiocarcinoma. There were 15 non-jaundiced (Group A) and 35 jaundiced patients (Group B). Data on demographic and clinical features, surgical procedures and pathological diagnoses were collected retrospectively. RESULTS: Preoperative mean serum levels of total bilirubin, aspartate aminotransferase, alanine aminotransaminase, alkaline phosphatase and gamma-glutamyltranspeptidase were statistically different between the groups. There was also a significant difference in the location of tumors. The distal tumors occurred in 9 non-jaundiced and 31 jaundiced patients (p=0.048). There were no significant differences between the characteristics and preoperative laboratory data of the patients with perihilar tumors and those with distal tumors. CONCLUSIONS: We believe that finding the disease in asymptomatic and non-jaundiced patients is very important for their prognosis. Further studies are needed and efforts should also continue to identify patients with suspicious findings.

[Laparoscopic partial gastrectomy for gastric submucosal tumor-indications and limitations of single-incision laparoscopic surgery].

Because gastric submucosal tumors can be treated by local resection without lymph-node dissection, laparoscopic local resection is widely used to manage relatively small tumors less than 5 cm in diameter. On the other hand, single-incision laparoscopic surgery (SILS) to perform laparoscopic cholecystectomy was feasible. SILS requires only a single incision in the umbilical region; it has better cosmetic outcomes than conventional laparoscopic surgery. The relative difficulty and ease of local gastric resection depends to a large part on tumor location and morphologic characteristics. Extraluminal submucosal tumor of the stomach can be locally resected by SILS using an automated suturing device regardless of tumor location. Intraluminal tumor located in the greater curvature of the gastric body can be treated by SILS, whereas intraluminal lesions located in the lesser curvature and near the gastric cardia or pylorus are difficult to manage by SILS. Laparoscopic and endoscopic cooperative surgery (LECS) is useful for resecting an appropriate amount of tissue at any site. In patients with lesions located near the gastric cardia or pylorus, closure with an automatic suture device may be difficult. Such patients should be switched to reduced-port surgery with a coaxial port, and hand-sewn closure is useful.

[Efficacy and safety of biweekly nedaplatin in combination with docetaxel as second-line chemotherapy in patients with unresectable or recurrent esophageal cancer].

There is no standard approach for second-line chemotherapy after a failure of the first-line regimen, fluorouracil and cisplatin -based chemotherapy in patients with unresectable or recurrent esophageal cancer. We have treated with biweekly nedaplatin (CDGP 40 mg/m²) in combination with docetaxe (l DOC 30 mg/m²) as second-line chemotherapy and investigated its efficacy and safety. Fifteen patients were retrospectively assessed in this study. Response rate (RR) and disease control rate (DCR) were 0 and 6.7%, respectively. Median time to progression( TTP) and median survival time( MST) were 2.1 and 7.0 months. Neutropenia and thrombocytopenia of grade 3 were seen in 4 (26.7%) and 1 (6.7%) patients, but no other serious adverse effects were detected. Based on the results, a biweekly nedaplatin/docetaxel regimen was safely received on an outpatient basis but not enough to provide a significant survival benefit. Quality of life and minimization of adverse effects are key considerations in second-line chemotherapy. Thereby, future trials should assess a quality of life in conjunction with different combination of active drugs and doses.

The impact of surgical outcome after pancreaticoduodenectomy in elderly patients.

BACKGROUND: The elderly population has increased in many countries. Indications for cancer treatment in elderly patients have expanded, because surgical techniques and medical management have improved remarkably. Pancreaticoduodenectomy (PD) requires high-quality techniques and perioperative management methods. If it is possible for elderly patients to withstand an aggressive surgery, age should not be considered a contraindication for PD. Appropriate preoperative evaluation of elderly patients will lead to their safer management. The purpose of the present study was to evaluate the safety of PD in patients older than 75 years and to show the influence of advanced age on the morbidity and mortality associated with this operation. PATIENTS AND METHODS: Subjects were 98 patients who underwent PD during the time period from April 2005 to April 2011. During this study, 31 patients were 75 years of age or older (group A), and the other 67 patients were less than 75 years old (group B). Preoperative demographic and clinical data, surgical procedure, pathologic diagnosis, postoperative course and complication details were collected prospectively and they were analyzed in two group. RESULTS: There was no statistical difference between patient groups in terms of gender, comorbidity, preoperative drainage, diagnosis, or laboratory data. Preoperative albumin values were lower in group A (P = 0.04). The mean surgical time in group A was 408.1 ± 73.47 min. Blood loss and blood transfusion were not significantly different between both groups. There was no statistical differences in mortality rate (P = 0.14), morbidity rate (P = 0.43), and mean length of hospital stay (P = 0.22) between both groups. Long-term survival was also no statistically significant difference between the two groups using the log-rank test (P = 0.10). CONCLUSION: It cannot be ignored that the elderly population is getting larger. We must investigate the management of elderly patients after PD and prepare further for more experiences of PD. If appropriate surgical management is provided to elderly patients, we suggest that PD will lead to no adverse effects after surgery, and PD can be performed safely in elderly patients. We conclude that age should not be a contraindication to PD.

[Highly advanced gastric cancer that responded to neoadjuvant combination chemotherapy with docetaxel/CDDP/S-1 (DCS)].

A 60-year-old male was found to have advanced gastric cancer and multiple lymph node metastases. Since curative surgery was concluded to be unfeasible, we tried neoadjuvant chemotherapy with the aim of controlling the lymph node metastasis. S-1 (80 mg/m2) was administered orally for two weeks then followed by 2-week rest period. CDDP (60 mg/ m2) and docetaxel (40 mg/m2) were simultaneously administered on day 1. Two courses of treatment resulted in marked shrinkage of the primary lesion and a reduction in size of the lymph nodes. The results were evaluated as a clinical PR based on RECIST, and radical resection was considered possible. The patient experienced a grade 3 leukocytopenia and neutropenia as adverse events of the chemotherapy. Total gastrectomy, splenectomy, and D2 lymph node dissection were performed with curative intent, and the postoperative course was uneventful. Histological examination of the surgical specimens revealed almost complete disappearance of cancer cells in the primary lesion in the stomach and complete disappearance in the lymph nodes. Pathological efficacy was Grade 2. The patient experienced a grade 3 appetite loss, and the adjuvant chemotherapy (S-1 regimen) was discontinued. The patient died of peritoneal dissemination eight months after the operation. We concluded that DCS as neoadjuvant chemotherapy was a promising strategy for patients with highly advanced gastric cancer because of its rapid antitumor effect.