Shinichi Kinami

Mapping sentinel nodes in patients with early-stage gastric carcinoma†

Nodal status in gastric carcinoma is related not only to prognosis but also to the extent of nodal dissection. However, a method for accurate assessment of nodal status during operation has not been established. This study aimed to map the sentinel nodes of gastric carcinoma and to estimate the clinical usefulness of sentinel node biopsy.

Reflux of duodenal or gastro‐duodenal contents induces esophageal carcinoma in rats

Esophageal adenocarcinoma arises from Barretts esophagus, which is induced by gastro‐esophageal reflux. This refluxate often contains duodenal contents, whose backflow triggers gastric carcinoma, suggesting the hypothesis that refluxed duodenal contents cause esophageal carcinoma. This study examines the role of duodenal and gastric reflux in the absence of exogenous carcinogens in esophageal carcinogenesis. Wistar male rats, 120 in all, each weighing approximately 250 g, were used. Three experimental procedures were performed to produce gastro‐duodeno‐esophageal reflux, duodeno‐esophageal reflux and gastro‐esophageal reflux, for comparison with 2 control procedures, Roux‐en‐Y reconstruction and a sham operation. The animals were fed a standard diet and were examined 50 weeks after surgery. While no carcinoma was found among the 16 gastro‐esophageal‐reflux, 11 Roux‐en‐Y and 12 sham‐operation animals, 10 of the 12 animals with gastro‐duodeno‐esophageal reflux (83%) and 10 of the 13 with duodeno‐esophageal reflux (77%) developed esophageal carcinoma. The difference between groups was significant (p < 0.001). Two animals with gastro‐duodeno‐esophageal reflux had esophageal double and triple carcinomas respectively. Of the 23 carcinomas, 16 were adenocarcinoma, 4 adenosquamous carcinoma, and 3 squamous‐cell carcinoma. Adenocarcinoma developed from the columnar‐lined epithelium near the esophago‐jejunostoma, while adenosquamous and squamous‐cell carcinoma arose from the squamous esophagitis. These observations demonstrate that refluxed duodenal contents per se are responsible for esophageal carcinogenesis.

Sentinel Node Mapping for Gastric Cancer: A Prospective Multicenter Trial in Japan

PURPOSE Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. PATIENTS AND METHODS Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines. RESULTS Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. CONCLUSION The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

Impact of the Biliary Diversion Procedure on Carcinogenesis in Barrett's Esophagus Surgically Induced by Duodenoesophageal Reflux in Rats

Objective:To determine whether the elimination of bile reflux in the established esophagojejunostomy model of Barretts esophagus (BE) will reduce or eliminate the risk of developing esophageal adenocarcinoma. Summary Background Data:Reflux of duodenal juice as well as gastric acid plays an important role in the pathogenesis of BE and adenocarcinoma. Duodenoesophageal reflux (DER) per se induces these diseases without carcinogen. However, it is unclear whether antireflux surgery induces regression of BE and prevents adenocarcinoma. Methods:Two hundred F344 male rats underwent one of following 3 operations: (1) total gastrectomy and esophagojejunostomy to induce DER, followed by killing after 20 (n = 13), 30 (n = 12), and 50 weeks (n = 30); (2) biliary diversion procedure, converted to Roux-en-Y method, to avoid bile regurgitation into the esophagus at 20 (n = 29) and 30 weeks (n = 32) after the operation to induce DER, followed by killing 50 weeks after initial operation; or (3) total gastrectomy and Roux-en-Y esophagojejunostomy followed by killing after 50 weeks served as controls (n = 28). Results:BE developed in more than half of the animals exposed to DER for 20 weeks, in more than 90% of rats with DER for 30 weeks, and in 100% of animals exposed to DER for 50 weeks. In the incidence and the length of BE, there is no difference between the animals that underwent biliary diversion at 20 (62%) and 30 weeks (94%) and those that had DER for 20 (54%) and 30 weeks (92%), respectively. Incidence of adenocarcinoma was significantly lower in the rats that underwent the biliary diversion procedure after 30 (19%) and 20 weeks (3%) than in the rats that had DER for 50 weeks (60%) (P < 0.005). None of the control animals that underwent Roux-en-Y esophagojejunostomy developed BE and carcinoma. Conclusions:It is likely that the converting procedure from the esophagojejunostomy to induce DER to biliary diversion does not lead to regression of BE but prevents the development of esophageal adenocarcinoma in the rats.

Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer

BackgroundWe investigated the presence and distribution of the sentinel and the non-sentinel node micrometastases using complete serial sectioning and immunohistochemical staining (IHC), to inspect whether lymph node micrometastases spread to the sentinel lymph nodes first.MethodsA total of 35 patients, who underwent gastrectomy with a sentinel lymph node biopsy for gastric cancer, were enrolled in this study. Total of 1028 lymph nodes of 35 patients having gastric cancer without metastasis of lymph node by permanent section with hematoxylin and eosin staining (H&E) were selected. There were 252 sentinel nodes and the other 776 were non-sentinel nodes. All nodes were sectioned serially and stained alternately with H&E and IHC. Lymph node micrometastases was defined as proving to be positive first either the IHC or the complete serial sectioning.ResultsMicrometastases were detected in 4 (11%) of the 35 patients, 6 (0.58%) of 1028 nodes. Of these 4 patients, 3 had micrometastases exclusively in sentinel nodes, and the other had micrometastasis in both sentinel and non-sentinel nodes. There was no patient who had the micrometasitases only in non-sentinel nodes.ConclusionThese results support the concept that lymph node micrometastasis of gastric cancer spreads first to sentinel nodes.

PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow

BackgroundWe propose a new classification for the location of gastric cancer — the PTD classification (i.e., zones P, T, and D; see below), with the zones classified according to the physiological lymphatic flow.MethodsThree hundred and thirty-six patients with T1 or small T2 gastric cancer who underwent sentinel node mapping at our hospital were enrolled. The relationship between the location of the gastric cancer and the physiological lymphatic flow derived from sentinel node mapping was investigated. Lymphatic basins were defined as lymphatic zones divided by the stream of stained lymphatic canals.ResultsOne hundred and forty-six patients underwent standard gastrectomy with more than D2 dissection and the other 190 patients underwent function-preserving gastrectomy with the omission of lymph node dissection outside the lymphatic basin. In the former group, the progression pattern of lymph node metastasis was observed; nodal metastasis occurred in sentinel nodes first, and rarely extended outside the lymphatic basin. In the latter group, none of the patients have had a recurrence. The PTD classification we propose is as follows: the dividing line between the proximal region (zone P) and the transitional region (zone T) is the line that links the point of the watershed between the left gastroepiploic artery and right gastroepiploic artery, to the point that is the inflow point of the first descending branch of the left gastric artery; and the dividing line between zone T and the distal region (zone D) is an arc at a radius of 8 cm from the pylorus. There were no lymphatic basins within the right gastric artery area for tumors located in zone T.ConclusionThe advantage of the PTD classification is that if the PTD classification were to be used as a guide for gastric resection procedures, preservation of the pylorus would become possible without diminishing the prognosis in patients with cT1N0 cancer located in zone T.

Characteristics and clinical relevance of postgastrectomy syndrome assessment scale (PGSAS)-45: newly developed integrated questionnaires for assessment of living status and quality of life in postgastrectomy patients.

BackgroundLack of a suitable instrument to comprehensively assess symptoms, living status, and quality of life in postgastrectomy patients prompted the authors to develop postgastrectomy syndrome assessment scale (PGSAS)-45.MethodsPGSAS-45 consists of 45 items in total: 8 items from SF-8, 15 items from GSRS, and an additional 22 items selected by 47 gastric surgeons. Using the PGSAS-45, a multi-institutional survey was conducted to determine the prevalence of postgastrectomy syndrome and its impact on everyday life among patients who underwent various types of gastrectomy. Eligible data were obtained from 2,368 patients operated and followed at 52 institutions in Japan. Of these, data from 1,777 patients were used in the current study in which symptom subscales of the PGSAS-45 were determined. We also considered the characteristics of the postgastrectomy syndrome and to what extent these symptoms influence patients’ living status and quality of life (QOL).ResultsBy factor analysis, 23 symptom-related items of PGSAS-45 were successfully clustered into seven symptom subscales that represent esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation, and dumping. These seven symptom subscales and two other subscales measuring quality of ingestion and dissatisfaction for daily life, respectively, had good internal consistency in terms of Cronbach′s α (0.65–0.88).ConclusionPGSAS-45 provides a valid and reliable integrated index for evaluation of symptoms, living status, and QOL in gastrectomized patients.

Section of the vagal celiac branch in man reduces glucagon-stimulated insulin release

The purpose of this study was to determine whether section of the celiac branch of the vagus nerve in man affects the insulin response to intravenous glucagon injection. Patients who received a subtotal gastrectomy with lymph node dissection for gastric carcinoma were divided into two groups: the celiac-preserved group (n = 16) and the celiac-sectioned group (n = 13). The hepatic branches of the vagus were preserved in both groups. The glucagon test was performed twice in each patient during the operation; before and after manipulation of the celiac branch. Blood samples were collected just before and 6 min after the injection. No difference in the mean increases in blood glucose, insulin and C-peptide levels were seen between the two groups before the nerve manipulation. In the celiac-preserved group, the glucagon stimulated glucose-related C-peptide ratio (x 10(-3) was 0.5 +/- 0.7 before the nerve manipulation and 3.5 +/- 3.0 after it, a significant difference (p < 0.01). In the celiac-sectioned group, this increase was not observed, the ratio was 0.7 +/- 0.6 before the nerve manipulation and 0.8 +/- 3.4 after. These results indicate that the vagal celiac branch in man may also be involved in the control of pancreatic insulin release.

Clinical evaluation of 3D-CT cholangiography for preoperative examination in laparoscopic cholecystectomy.

Abstract: Three-dimensional-computed tomography (3D-CT) cholangiography is a 3D shaded surface display image of the biliary tract obtained by using helical CT after intravenous cholangiography or cholangiography per percutaneous transhepatic cholangio-drainage tube. We investigated whether 3D-CT cholangiography could provide a useful image, for preoperative examination in laparoscopic cholecystectomy. Sixty-five patients with biliary diseases were examined by 3D-CT cholangiography. Helical scanning was performed on a Proceed Accell (GE Medical Systems, Waukesha, WI, USA). Three-dimensional images were created using an independent workstation. A clear image of the common bile duct was obtained for all patients (100%) by 3D-CT cholangiography. The gallbladder was well visualized in 54 (93%) and the cystic duct was shown to be opacified in 55 (95%) of the 58 patients with a gallbladder. Thirty-one patients were diagnosed as having gallstones by 3D-CT cholangiography (sensitivity, 72.1%; specificity, 100%; accuracy, 79.3%), while 43 were diagnosed as having cholecystolithiasis by ultrasonography. The advantages of 3D-CT cholangiography were a low level of invasiveness, easily obtained images compared to those obtained with endoscopic retrograde cholangiography (ERC), good opacification, and provision of a three-dimensional understanding of the biliary system, especially of the cystic duct. When combined with ultrasonography and routine liver function tests, 3D-CT cholangiography was considered very useful for obtaining information before laparoscopic cholecystectomy. It allowed the omission of ERC in many patients who were considered to have no common bile duct stone, by employment of 3D-CT cholangiography.

Convergence to diffusion waves of the solutions for benjamin-bona-mahony-burgers equations

This paper is concerned with the large-time behavior of solution of the Cauchy problem for the Benjamin-Bona-Mahony-Burgers equation. We prow that the solution unique globally exists and time-asymptotically tends to its corresponding diffusion wave, when the initial perturbation is small enough. The corresponding diffusion wave is constructed by the heat equation or the Burgers equation. In particular, we obtain the convergence rates in Lq-spaces (2≤q≤∞). The mathematical proof is based on the Fourier transform method and the energy method.Furthermore, we take the numerical computations on such a problem. The numerical simulations show that the convergence rates obtained theoretically seem to be sharp