Kumagai Y

Differences in the Definitions Used for Esophageal and Gastric Diseases in Different Countries Endoscopic Definition of the Esophagogastric Junction, the Precursor of Barrett's Adenocarcinoma, the Definition of Barrett's Esophagus, and Histologic Criteria for Mucosal Adenocarcinoma or High-Grade Dysplasia

Background: Definitions and opinions in the field of gastroenterology vary widely in different countries. Methods: Here we discuss four such important differences: the definition of the esophagogastric junction (EGJ), the possible precursor of Barrett’s adenocarcinoma, the definition of Barrett’s esophagus (BE), and the histologic criteria for mucosal adenocarcinoma. In addition, we consider which definitions and opinions might be valid and practical. Results: There are two different endoscopic definitions of the EGJ. Our research on German subjects has indicated that many small Barrett’s adenocarcinomas may arise not in the intestinal-type but in the cardiac-type mucosa. If an area of columnar-lined esophagus (CLE) is only partially involved by intestinal metaplasia, then the latter cannot always be demonstrated in biopsy specimens. Therefore, we do not think that a definition of BE as CLE with histologic intestinal metaplasia is practical. Data from the literature have shown that many cases of high-grade dysplasia (HGD) progress to carcinoma within a very short time, and in most such cases the carcinoma has been underdiagnosed in biopsy specimens as HGD. Conclusion: With regard to the definitions and opinions, an exchange of views between gastroenterologists in North America, Europe, and Japan would be desirable.

Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients

The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5′-untranslated region (UTR) and 6-bp deletions in the 3′-UTR of thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S-transferase π (GSTP1; IIe105Val), GST θ1 (GSTT1; deletion) and GST μ1 (GSTM1; deletion) and the two DNA-repair genes, excision repair cross-complementing-1 (ERCC1; Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and the clinical outcome, including drug response, progression-free survival (PFS), overall survival (OS) and the incidence of peripheral neuropathy, were evaluated. Patients with the GSTP1-105 A/A genotype had poor responses to mFOLFOX6 treatment compared with those with the GSTP1-105 A/G and G/G genotypes (P=0.01). The median PFS of patients with the ERCC2-751 A/A genotype tended to be longer than that of patients with the ERCC2-751 A/C genotype (P=0.05). Patients with the TS-3′-UTR −6/−6 genotype had a significantly longer OS compared with patients with other genotypes (P=0.003). A statistically significant association between the incidence of peripheral neuropathy higher than grade 2 and the GSTP1-105 (P=0.03) and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression analyses. Results demonstrated that polymorphisms in GSTP1-105, ERCC2-751 and the 3′-UTR of TS may be a statistically significant predictors of clinical outcome. GSTP1-105 and GSTM1 genotypes may be useful markers of severe peripheral neuropathy in MCRC patients treated with 5-FU/oxaliplatin as first-line chemotherapy.

Treatment strategy for blunt hepatic trauma: analysis of 183 consecutive cases.

BACKGROUND/AIMS Non-operative management of hemodynamically stable trauma has proven successful; however laparotomy for hemodynamically unstable patients is still insufficient. We evaluated the results of treating blunt hepatic injury and appraised the appropriate surgical procedures. METHODOLOGY We analyzed the demographics, vital status, and severity of hepatic and concomitant organ injuries of 183 consecutive patients with blunt hepatic injuries between January 2001 and December 2008, retrospectively. RESULTS Twenty five of 183 patients died before the treatment was selected. The initial management was operative for 24 and non-operative for 134, 15 of whom later required laparotomy. Of the 134 treated non-operatively, 2 died after arterial embolization for pelvic fractures. Twelve patients died postoperatively: 6 of the hepatic injury and 6 of concomitant organ injuries. Considering Liver Injury Scale of operated patients, there was no liver-related death with grades I-III; however, liver-related mortality of grades IV and V was 37.5%. The incidence of liver-related deaths after anatomical resection was 0% of patients with grade IV, but 50% of patients with grade V, despite anatomical resection being the only effective procedure for grade V. CONCLUSIONS The results of anatomical resection for grade IV is satisfactory, but additional strategies are still required for grade V.

Histopathological diagnosis of adenocarcinoma in Barrett's esophagus.

The present review describes the histological markers of Barretts esophagus (BE) that make it possible to distinguish between Barretts carcinoma (BC) and gastric carcinoma. With regard to high‐grade dysplasia, the indications for endoscopic resection (ER) or major surgery for management of BC cannot be decided on the basis of biopsy histology, and the choice between them should be made according to BC invasion depth. Therefore, we recommend that the term ‘well‐differentiated tubular adenocarcinoma’ be used rather than ‘high‐grade dysplasia’ (intraepithelial neoplasia). High‐grade dysplasia is regarded as BC in Japan and other countries such as Germany. Such lesions should not be treated by endoscopic ablation but by ER, because components of invasive carcinoma are frequently present in the mucosa and submucosa, and knowledge obtained from ER samples is needed for additional therapy. Further studies on the relationship between the incidence of nodal metastasis and mucosal depth in mucosal BC are needed to decide the indications for ER. Suchstudies should involve subserial microscopic examination of slices 2–3 mm thick. To resolve the issue of regression of high‐grade dysplasia, international experts in gastroenterological pathology need to conduct histopathological reviews of the first and last samples taken from such cases, as there are large differences between North American, European, and Japanese pathologists in the criteria used for histological diagnosis of dysplasia and adenocarcinoma without clear invasion, and both interobserver and intraobserver variations have been reported. Future studies will need to focus on which carcinomas are curable by ER.

Prognostic Factors for Stage IV Gastric Cancer

recommend selectionfrom among 5 treatments for stage IV patients inclinical practice: surgery (extended or palliative),chemotherapy, radiation therapy or palliative care.Principles are still controversial, and clinical study isadvocated. The nature of the disease does not allowus to conduct prospective studies; however, retro-spective study plays an important role by means ofclinical study.This study is a retrospective study based onclinical practice and aims to clarify the favorablefactors contributing to better prognosis of stage IVgastric cancer patients. Furthermore, we aim toassess the optimal treatment strategies.

Curative resection of a huge malignant pancreatic endocrine tumor by pancreatoduodenectomy with portal and superior mesenteric vein resection and reconstruction using the right ovarian vein: report of a case.

Nonfunctioning pancreatic endocrine tumors (PETs) are rare and generally asymptomatic. A 68-year-old woman who had refused treatment for a pancreatic mass, revealed by ultrasonography to be 55 mm in diameter, was referred to us again 29 months later with jaundice. Investigations showed an 82-mm tumor in the head of pancreas, exposed from the papilla of Vater to the duodenal lumen. After biliary decompression and drainage, we performed pancreatoduodenectomy with resection of the portal vein and superior mesenteric vein, followed by reconstruction using a cylindrically customized autologous graft harvested from the right ovarian vein. The tumor was resected curatively. Microscopically, it consisted of trabecular and ribbon-like arrangement of neoplastic cells. Immunohistochemical staining was positive for chromogranin A and synaptophysin and negative for insulin, gastrin, glucagons, somatostatin, and pancreatic peptide. Although metastasis was detected in a lymph node along the superior mesenteric vein with perineural invasion, the portal and superior mesenteric veins had not been invaded. The diagnosis was well-differentiated nonfunctioning PET. The patient had an uneventful postoperative course, and there has been no evidence of recurrence in 12 months.

High resectability of colorectal liver metastases with aggressive chemotherapy in the era of molecular target-based agents.

BACKGROUND/AIMS Advances in chemotherapy have expanded the resectability of colorectal liver (CRC) metastases. We studied treatment results in CRC patients with liver metastases in the era of molecular target-based agents. METHODOLOGY Based on data collected retrospectively, we analyzed the demographics, operative and pathological outcomes, and adjuvant chemotherapy, of 91 consecutive CRC patients with liver metastases treated between January, 2008 and June, 2010. RESULTS Of the 91 patients, 42 (46.2%) underwent liver resection (group 1), 41 underwent only resection of the primary tumor without hepatectomy (group 2), and 8 underwent palliative surgery (group 3). According to multivariate analysis, resection of liver metastases was significantly influenced by the number of metastases and the existence of extrahepatic metastases. Disease-free survival (DFS) differed significantly between patients who received adjuvant therapy and those treated by surgery alone (p<0.001). The regimen (p=0.01) and duration (p<0.0001) of adjuvant chemotherapy also affected DFS. Overall survival after 1 and 3 years was 97.6% and 94.0%, respectively, in group 1, 71.9% and 30.6% in group 2, and 33.3% and 0% in group 3. CONCLUSIONS Although the observation period was short, our findings suggest that high resectability and effective chemotherapy will prolong the survival of patients with colorectal liver metastases.

Successful combination therapy of radical liver resection with 5-fluorouracil/leucovorin, oxaliplatin, plus bevacizumab for ascending colon cancer with pulmonary and 43 liver metastases: report of a case.

At the time of diagnosis, 20% to 25% of patients with colorectal cancer already have liver metastases, the presence of which is a most important prognostic factor. A 64-year-old man was admitted to our hospital for investigation of anemia and multiple liver tumors. Examinations revealed ascending colon carcinoma with more than 40 liver metastases and 2 lung metastases. We performed right hemicolectomy with lymph node dissection, which was followed by 5-fluorouracil/leucovorin, oxaliplatin, plus bevacizumab (FOLFOX-BV). After 4 courses of chemotherapy, the lung metastases were in complete remission and the liver metastases had shrunk. We suggested the option of radical liver resection, but the patient declined initially as he had not suffered any severe side effects of FOLFOX-BV. After 23 courses of the chemotherapy, he agreed to undergo hepatectomy. We performed extended right lobectomy with partial left and caudal lobe resection. All of the macroscopic metastatic lesions were resected. Histopathologically, viable cancer cells were recognized in 7 of the 43 liver metastatic lesions. Postoperatively, FOLFOX-BV was restarted and continued for 10 months. At the time of writing, 15 months after the hepatectomy, the patient was well without evidence of recurrence of the cancer.

Favorable response after gemcitabine-radiotherapy for invasive pancreatic intraductal papillary mucinous neoplasm: a case report.

The efficacy of chemoradiotherapy for invasive pancreatic ductal carcinoma derived from an intraductal papillary mucinous neoplasm (IPMN) has not been established. The subject of the present report was a 53-year-old man admitted for the treatment of IPMN. The tumor, located in the pancreatic body, was of the mixed type of IPMN, and it involved the branch duct, where it was 38 mm in diameter, and the main duct, where it was 6 mm in diameter. Distal pancreatectomy was performed and the postoperative course was uneventful; however, histopathologic diagnosis revealed invasive ductal carcinoma with a positive surgical margin in the pancreatic duct. Although total pancreatectomy was recommended, chemoradiotherapy (50.4-Gy irradiation and gemcitabine) was preferred by the patient. At 9-month follow up, computed tomography and magnetic resonance imaging showed a cystic mass at the surgical margin of the pancreas. Endoscopic ultrasonography showed a 44-mm cystic lesion with nodules in the remnant pancreas, on the basis of which he underwent total pancreatectomy. Pathologic examination of the resected specimen revealed absence of the epithelium at the surgical margin of the main pancreatic duct, and malignant cells were not detected.