[Investigation of marginal ulcer after pancreatoduodenectomy].

BACKGROUND: Marginal ulcer after pancreatoduodenectomy (PD) is a relatively common complication, but if massive bleeding or ulcer perforation occurs together with the marginal ulcer, this condition may be fatal. OBJECTIVE: To identify the risk factors and management of marginal ulcer after PD. METHODS: In all, 438 patients who underwent PD from 2003 to 2017 were retrospectively reviewed and analyzed. After surgery, all patients were administered a histamine H2 receptor antagonist (H2RA) or a proton pump inhibitor (PPI), which was continued after discharge. Marginal ulcer was diagnosed by endoscopy or surgery. The risk factors for marginal ulcer were then investigated using univariate and multivariate analyses. RESULTS: After a median follow-up time of 2.7 years, 29 patients (6.6%) developed marginal ulcer. Seventeen patients developed marginal ulcer within 1 year after PD, and 7 patients developed marginal ulcer more than 3 years after PD. All 8 patients who underwent surgery for the treatment of marginal ulcer developed acute peritonitis. Two patients with acute peritonitis died within 1 month after surgery. A multivariate analysis found that discontinuation of PPI treatment was the only independent risk factor for marginal ulcer development (P<0.001). In contrast, sex, age, primary disease, procedure, operation time, volume of blood loss, pancreatic texture, development of postoperative pancreatic fistula, postoperative complications, poor glycemic control after PD, and discontinuation of H2RA therapy after PD were not significantly different between the patient group that developed marginal ulcer and the patient group that did not. Sixteen patients were not treated with antacids at the time of marginal ulcer development. The reason for discontinuation of antacids was the decision of the family physician in 8 cases and the decision of the patient in 3 cases. CONCLUSION: Marginal ulcer can still develop a long time after PD, and sometimes, it may be fatal. PPI administration should be continued even after a long time has passed, although this therapy is often discontinued for various reasons. It is therefore important for family physicians and patients to recognize the danger of marginal ulcer after PD.

Human Telomerase Reverse Transcriptase Gene Promoter Mutation in Serum of Patients with Hepatocellular Carcinoma.

BACKGROUND: Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC. OBJECTIVE: A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study. METHODS: The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS). RESULTS: The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses. CONCLUSIONS: The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.

Impact of Body Mass Index on Survival of Pancreatic Cancer Patients in Japan.

The impact of body mass index (BMI) on postoperative survival in Japanese patients with pancreatic cancer is unclear. We examined the relationship between preoperative BMI and the prognosis of Japanese patients who underwent surgery for pancreatic cancer to determine whether BMI affects these patients' prognosis. Of the patients who underwent pancreatectomy between January 2004 and August 2015 at our institution, 246 were pathologically diagnosed with pancreatic tubular adenocarcinoma; the cancer was located in the pancreatic head (n=161) and in the body and tail (n=85). We classified the patients by BMI: underweight (n=22), normal weight (n=190), and overweight/obese (n=34) groups. We retrospectively analyzed medical records for patient characteristics, lesion location, disease stage, postoperative complications, chemotherapy, and prognosis. Lesion location, disease stage, postoperative complications, and chemotherapy were not significantly different among the BMI groups. The median survival times were as follows (days): all patients, 686; underweight, 485; normal weight, 694; and overweight/obese, 839. In a multivariate analysis, after adjusting for competing risk factors, low BMI was associated with an increased risk of death (normal weight: HR 0.58, p=0.038; overweight/obese: HR 0.54, p=0.059). High BMI was not found to be a postoperative factor for poor prognosis in Japanese pancreatic cancer patients.

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma.

BACKGROUND AND AIM: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed. METHODS: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice. RESULTS: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6). CONCLUSIONS: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

[A case of a patient who underwent resection of the remnant pancreatic cancer following a distal pancreatectomy for invasive ductal carcinoma].

Herein, we report the case of a patient who underwent resection of the remnant pancreas for pancreatic cancer following a distal pancreatectomy for invasive ductal carcinoma. An 81-year-old woman underwent a distal pancreatectomy. The tumor was found to be pancreatic cancer. The tumor was histologically diagnosed as a poorly differentiated tubular adenocarcinoma (Stage I). An abdominal computed tomography (CT) performed 17 months later revealed a 13 mm tumor in the remnant pancreatic head. A remnant pancreatectomy was performed. The histological diagnosis was a moderately differentiated tubular adenocarcinoma (StageIII). Remnant pancreatic cancer is rare following a pancreatectomy for invasive ductal carcinoma. The course of remnant pancreatic cancer can be followed with imaging. Long-term follow-up of patients who have undergone a pancreatectomyis, therefore, essential.

Long-term effect of external beam radiotherapy of optic disc hemangioma in a patient with von Hippel-Lindau disease.

An 18-year-old woman with a 2-year history of hypertension and headache was diagnosed with noradrenalin-secreting bilateral adrenal pheochromocytomas with paragangliomas in the background of von Hippel-Lindau disease with family histories and a missense mutation, 712C to T (Arg167Trp) in the VHL gene. She had optic disc hemangioma in the left eye which gradually enlarged and caused serous retinal detachment on the macula in one year. Low-dose external beam radiation (20 Gy) was administered to the left eye using a lens-sparing single lateral technique. She underwent craniotomy for cerebellar hemangioblastoma at the age of 22 years and total pancreatectomy for multiple neuroendocrine tumors at the age of 24 years. In the 6-year follow-up period after the radiotherapy, the optic disc hemangioma gradually reduced in size and its activity remained low, allowing good central vision to be maintained. External beam radiation is recommended as a treatment option for the initial therapy for optic disc hemangioma.

A single-institution retrospective analysis of gastric carcinoma with positive peritoneal lavage cytology and without serosal invasion: A case series.

BACKGROUND AND OBJECTIVES: Peritoneal dissemination of gastric cancer is often associated with serosal infiltration. The aim of this study was to evaluate the clinical importance of peritoneal lavage cytology in patients with gastric carcinoma without serosal invasion. The incidence and impact on prognosis of positive cytology were analyzed. METHODS: Of 2768 patients with gastric cancer, outcomes and pathological characteristics of 973 patients were reviewed retrospectively. All patients underwent peritoneal lavage at laparotomy for curative or palliative resection of gastric cancer between 1999 and 2017. Among these, 479 who underwent surgery from January 1999 to March 2012 were also reviewed to analyze 5-year survival. RESULTS: Of 973 patients enrolled, 338 (35%) did not have serosal invasion, and peritoneal cytology was positive in 4/338 (1.2%). Of these four patients, one had submucosal invasion and three had muscularis propria invasion. Of 635 patients with serosal invasion, peritoneal cytology was positive in 74/635 (12%). Of 479 patients reviewed for survival, cytology was positive in 32/479, with 3/32 (9%) surviving for five years, and cytology was negative in 447 patients with 266/447 (60%) surviving for five years. CONCLUSIONS: Cytologic evaluation should be routinely performed in patients with early-stage gastric cancer.

Peritonitis with small intestinal perforation caused by a plastic bread bag clip: A case report.

INTRODUCTION: Cases of a foreign body ingestion often require surgical treatment due to perforation or penetration. There is a possibility that plastic bread bag clips also cause serious adverse events when they are ingested. PRESENTATION OF A CASE: We report a rare case of peritonitis with small intestinal perforation caused by a plastic bread bag clip that needed surgical treatment. A 47-year-old man was taken to our hospital because of abdominal distension and vomiting. A computed tomography test demonstrated findings of small intestinal perforation, and a high-density object was seen in the jejunum. During emergency surgery, it was discovered that a plastic bread bag clip had caused the perforation. DISCUSSION: Some cases of gastrointestinal tract perforation or bleeding due to the ingestion of bread bag clips have been reported overseas. Because bread bag clips are normally radiolucent, they are impossible to discover when accidentally ingested, so diagnosis is difficult unless the patient remembers the incident. The shape of plastic bread bag clips is unique and can result in a trap-like effect, which prevents easy removal once ingested. CONCLUSION: Bread bag clips need caution in handling, and in cases of accidental ingestion, careful observations should be made to allow for removal within reach of upper GI endoscopy. The following case report has been reported in line with the SCARE criteria [1].

Modified Blumgart anastomosis with the "complete packing method" reduces the incidence of pancreatic fistula and complications after resection of the head of the pancreas.

BACKGROUND: Postoperative pancreatic fistula (POPF) and its complications remain problems. This study evaluated combination treatment with modified Blumgart anastomosis and an original infection control method (complete packing method) following pancreatic head resection. METHODS: This study included 374 consecutive patients who underwent pancreatic head resection: 103 patients underwent Cattell-Warren anastomosis (CWA); 170 patients underwent modified Kakita anastomosis (KA); and 101 patients underwent modified Blumgart anastomosis with the complete packing method (BAC). The outcomes of the KA and BAC groups were compared statistically. RESULTS: The POPF rate was significantly lower in the BAC group than in the KA group (28.8% vs 2.97%; p < 0.01). The overall postoperative complication rate, including SSI and postoperative hemorrhage, was significantly lower in the BAC group. CONCLUSIONS: The combination of modified Blumgart anastomosis and the complete packing method is a simple and useful method for reducing the incidence of POPF and postoperative complications.

Outcomes of 1,639 hepatectomies for non-colorectal non-neuroendocrine liver metastases: a multicenter analysis.

BACKGROUND: Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear. METHODS: Data regarding 1,639 hepatectomies performed between 2001 and 2010 for 1,539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed. RESULTS: The five most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 90% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1,465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the five frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type. CONCLUSIONS: Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor.

Intra-Aortic Balloon Occlusion (IABO) may be useful for the management of secondary aortoduodenal fistula (SADF): A case report.

INTRODUCTION: Secondary aortoduodenal fistula (SADF) is a rare but life-threatening complication after aortic reconstruction. Although a number of reports describing treatments for SADF have been published, the optimal management is unclear. A review of the literature suggested methods of reconstruction, control of bleeding, and reduction of infection in the management of SADF. The most important factor for acute intervention is controlling the bleeding from the fistula. We report one case treated using intra-aortic balloon occlusion (IABO) for SADF. PRESENTATION OF A CASE: We describe a case of secondary aortoduodenal fistula that occurred seven years following aortobifemoral reconstruction for abdominal aortic aneurysm. DISCUSSION: Early control of bleeding is essential for survival of the patient. Emergency laparotomy or endovascular stenting frequently have been chosen as interventions, although each approach has significant limitations. Emergency laparotomy for patients with hemodynamic instability may create excessive physiologic stress, and endovascular stenting may not be available at every surgical facility. The use of IABO for cases of intraperitoneal bleeding due to trauma has been previously described. IABO is relatively easy to implement, and enabled us to control the bleeding from the aorta more rapidly than other strategies. CONCLUSION: Based on a review of the literature and our own experience, IABO should be considered as one option for the management of SADF.

Hereditary Spherocytosis in a Middle-aged Man Complicated with Common Bile Duct Stones.

Hereditary spherocytosis is the most common form of hemolytic anemia and is characterized by spherical, osmotically fragile erythrocytes that are selectively trapped by the spleen. Hereditary spherocytosis is typically diagnosed in childhood. We herein experienced a rare case of hereditary spherocytosis diagnosed in middle age. The patient presented with cholelithiasis and hyperbilirubinemia. He had no anemia and was asymptomatic with mild splenomegaly. In the differential diagnosis of these symptoms, the possibility of hereditary spherocytosis should be considered, even in patients who are middle-aged and lack anemia.

Genome aberrations observed by restriction landmark genome scanning analysis of chromosomal DNA in various types of primary hepatocellular carcinoma.

BACKGROUND/AIMS: The genes responsible for hepatocellular carcinoma have not been identified. To identify the relevant genes of hepatocellular carcinoma, detailed and comprehensive information of genomic aberrations must be obtained. To reveal the chromosomal aberrations in hepatocellular carcinoma, we carried out a restriction landmark genome scanning analysis of various types of hepatocellular carcinoma. METHODOLOGY: Samples of various types of hepatocellular carcinoma, including two with multinodular-hepatocellular carcinomas, one hepatocellular carcinoma showing nodules in a nodule pattern, one hepatocellular carcinoma metastasized to different tissues, three small (< 2.0 cm) hepatocellular carcinomas and four large (> 5.0 cm) hepatocellular carcinomas were examined by the restriction landmark genome scanning method with corresponding non-hepatocellular carcinoma tissues. Restriction enzyme Not I was used as a landmark enzyme, Eco RV was used as a fragmentation enzyme, and Hin fI was used as a digestion enzyme in the gel for two-dimensional electrophoresis. RESULTS: We observed spot aberrations with different origins. Frequently observed spot aberrations originated from the change in the methylation status of repetitive sequences. No clear correlation between the pathological grade and the number or type of spot aberrations was observed. CONCLUSIONS: We demonstrated that major aberrations of restriction landmark genome scanning spots originated from the change of methylation status in hepatocellular carcinoma.

A case of follicular cholangitis mimicking hilar cholangiocarcinoma.

Follicular cholangitis is a sclerosing cholangitis with hilar biliary stricture that must be differentiated from both immunoglobulin G4-related sclerosing cholangitis and primary sclerosing cholangitis. This disorder is extremely rare and difficult to distinguish from hilar biliary cholangiocarcinoma. We report here a case of a Japanese female patient in her 60s with this disease. The patient visited a family doctor for itching and general fatigue. Blood examination showed elevated hepatobiliary enzyme levels. Various imaging studies showed dilation of the bilateral intrahepatic bile duct and wide stenosis from the proximal bile duct to the right and left hepatic duct. They also showed the enlargement of multiple lymph nodes in the hepatoduodenal ligament, periaorta, and mesocolon. Based on endoscopic retrograde cholangiopancreatography-directed brush cytology, we diagnosed this patient with hilar cholangiocarcinoma and performed left trisegmentectomy of the liver. The pathology results showed that the wall from the bilateral hepatic duct to the proximal bile duct had thickened irregularly with dense fibrosis and a marked formation of lymph follicles. The mucosal epithelia did not have malignant findings. The diagnosis was follicular cholangitis. This case indicates that follicular cholangitis should be considered as a differential diagnosis of hilar biliary stricture.

Diagnosis of a solid pseudopapillary neoplasm using EUS-FNA.

A woman in her 50s was found to have a pancreatic mass on abdominal ultrasound. The tumor measured 40 mm in diameter and included a cystic lesion and calcification. In this case, we suspected a diagnosis of solid pseudopapillary neoplasm (SPN) due to the findings observed on various images. However, we were unable to exclude the possibility that the lesion was a neuroendocrine tumor. Therefore, we performed endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA). In addition, in order to confirm the diagnosis of SPN, we performed minimized resection (segmental pancreatectomy). Obtaining a definitive preoperative diagnosis of SPN using EUS-FNA can guide the surgical approach.

TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers.

Tumor protein p53 (TP53) is the best-known tumor suppressor gene and plays a crucial role in carcinogenesis. The TP53 Arg 72 Pro polymorphism has been reported to be a risk factor for several types of cancer, but its association with pancreatic cancer has not been fully evaluated. Therefore, we investigated the effects of this polymorphism on pancreatic cancer in relation to smoking and drinking habits by examining the distribution of the SNP genotypes in 226 pancreatic cancer patients and 448 healthy controls. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro were found to be 37, 49 and 15% in the pancreatic cancer cases and 44, 46 and 10% in the controls, respectively. Compared to the controls with the Arg/Arg genotype, cases with Pro/Pro homozygosity exhibited a significantly increased risk [adjusted odds ratio (OR)=1.70; 95% confidence interval (CI) 1.01-2.88]. In stratified studies, the association was particularly strong in males (OR=2.62; 95% CI 1.32-5.23), particularly in those smoking in excess of 20 pack-years and drinking in excess of 23 g ethanol/day (OR=5.02; 95% CI 1.12-22.51). We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.