Search

BACKGROUND AND OBJECTIVES A variety of minimal invasive treatment strategies for early gastric cancer without reducing the curability have been introduced, however, the indications for the local resection of early gastric cancer have not been precisely established. METHODS Two approaches are adopted in this study to elucidate indications for local resection. One is a retrospective review of surgically resected, postoperatively histologically proven early gastric cancers between 1976 and 1996 (611 patients), and the other is the patient selection from those who underwent modified D(1) lymphadenectomy in a prospective manner between 1987 and 1996, based on the preoperative and intraoperative diagnoses of mucosal, node negative, nonpalpable gastric cancer (125 patients). In these approaches, patterns of nodal involvement in association with clinicopathological characteristics of gastric cancer were investigated. RESULTS The depressed with ulceration type and histologically high grade type were predominant characteristics of mucosal, node positive gastric cancer patients. Of these patients, after the exclusion of those who were diagnosed to have submucosal or advanced cancer preoperatively or who had palpable cancer intraoperatively, the gastric cancer < or =4 cm in maximum diameter had positive nodes confined to only one station adjacent to the cancer without simultaneous nodal involvement in the other stations. CONCLUSIONS Local resection can be performed for gastric cancers < or = 4 cm in maximum diameter that meet our criteria for modified D(1) lymphadenectomy, in association with the frozen section confirmation of cancer negative in the simultaneously dissected lymph nodes in the stations adjacent to the cancer. The adjacent lymphadenectomy and frozen section examination make the application of local resection possible for a wider segment of patients.

Background and Objectives Many combination patterns of chemotherapy and radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer indicate that the optimal doses of chemotherapeutic agents and of chemotherapy and radiotherapy regimens remain unclear. The feasibility and promising outcome of our newly developed definitive CRT for nonsurgical management of esophageal cancer, essentially based on the theoretical backgrounds of the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, is investigated. Methods Six nonoperated esophageal cancer patients were treated by daily concurrent CRT, which consisted of continuous 5-fluorouracil administration with leucovorin, combined with a low dose of daily cisplatin administration before each fraction of radiation. Response to CRT and toxicities and survivals were evaluated. Results Complete and partial responses were seen in 2 patients each. Histologic examination of the biopsy specimens in the primary site showed no cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other 2 patients showed good-quality survival, having dramatic relief from dysphagia. There were no treatment-related deaths Conclusions The daily concurrent CRT is rational and promising and compares well with other series of definitive CRT. The CRT based on the theoretical background is feasible as a nonsurgical management option for esophageal cancer patients. J. Surg. Oncol. 2000;74:134–137. © 2000 Wiley-Liss, Inc.

Background: Early gastric cancer (EGC) often coexists with peptic ulcer. In this study we investigated the roles of peptic ulcer in the carcinogenesis and extension of gastric cancer. Methods: The clinicopathological characteristics of EGC and peptic ulcer and their relationship, as well as that of the background intestinal metaplasia, were compared among the following three groups: patients with peptic ulcer only inside the EGC (Contained group, 53 patients); patients with peptic ulcer only outside the EGC (Separate group, 26 patients); and patients of EGC with no peptic ulcer (Absent group, 43 patients). Results: In the Separate group, a male preponderance was observed (P = .006), and all EGCs developed in the middle or lower third of the stomach (P = .06). Most of the EGCs were an intestinal type of cancer with severe background intestinal metaplasia. Topographically, 88% of the peptic ulcers in the Separate group developed proximal to the EGC. On the other hand, in the Contained group, most EGCs developed in the middle third of the stomach with an intestinal/diffuse type ratio of 1:1. Peptic ulcers inside the EGC were significantly more shallow than those that developed outside the EGC (P = 0.008). Although the incidences of submucosal cancer were nearly the same among the three groups, the maximum cancer diameter tended to be increased in the Contained group compared to that in the Absent group, and the incidence of lymph node involvement tended to be higher in the Contained group (8%) as compared with the other two groups (4%–5%). Conclusions: These results suggest that peptic ulcer outside the EGC contributes to the development of the intestinal type of EGC, with the background of more severe intestinal metaplasia during the peptic ulcer healing processes, whereas peptic ulcer inside the EGC develops secondary to EGC and favors cancer extension and metastasis. Peptic ulcer associated with EGC can be considered to exert different biological roles in the carcinogenesis or extension of ECG according to the location of the peptic ulcer.

Adenocarcinoma arising at an ileostomy is uncommon, and only 29 cases have been reported in the literature. The case of a 54-year-old man who developed an adenocarcinoma at a Brooke ileostomy is reported. The ileostomy had been fashioned 21 years earlier after proctocolectomy for familial adenomatous polyposis (FAP). A wide local excision of the stoma was performed, and a new Brooke ileostomy was fashioned on the opposite side of the abdomen. Histopathologic examination revealed a well-differentiated adenocarcinoma with early invasion of the submucosa. On hematoxylin and eosin staining, the ileal mucosa adjacent to the tumor showed signs of colonic metaplasia, including loss of villous architecture and a reduced number of Paneth cells. Mucin staining using the high iron diamine-alcian blue stain demonstrated a mixture of sulfomucin and sialomucin in the ileal mucosa near the tumor, confirming colonic metaplasia. Ileostomy site carcinogenesis can be attributed to both the colonic metaplasia and the inherent nature of FAP or ulcerative colitis (UC), where colonic mucosa is susceptible to adenoma formation or dysplasia. Longstanding ileostomies in patients with FAP or UC should be followed to exclude the development of adenoma, dysplasia, or cancer.

Recent observations and our experience that histologic types of gastric cancer related significantly to patterns of recurrence prompted us to develop intraoperative and postoperative chemotherapy based on the preoperatively diagnosed histologic types of cancer and to evaluate its effectiveness by a prospective randomized trial. This chemotherapy regimen consisted of the intraoperative administration of mitomycin C (MMC) and postoperative administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT) (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were randomly assigned to one of three treatment groups: no intraoperative chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.

Background: A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. Methods: Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m 2/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m 2/day, days 1-5, and 5 or 10 mg/m 2/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. Results: All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-c1assification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. Conclusions: These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal cancer patients.

Primary malignant melanoma of the esophagus is a rare disease, accounting for 0.1_??_0.4% of all esophageal neoplasms. Metastases are common to the liver, mediastinum, mediastinal glands and lung. We present a case of the disease with metastases to the skin, colon and mammary gland. There have been no reported cases of colon and mamma metastasis, and skin is also a rare site for metastasis. A 78-year-old woman was reffered to our hospital for weight loss and dysphagia. She had multiple subcutaneous tumors and a solitary mammary tumor. Esophagoscopy revealed a large polypoid tumor with foci of black pigmentation in the lower esophagus. Colonoscopy disclosed a small submucosal tumor. Biopsies from these tumors were all positive for HMB-45 staining, confirming the diagnosis of malignant melanoma. Junctional activity was not found in the tissue of the esophageal tumor, but its size, characteristic polypoid figure, melanosis of the adjacent mucosa and the absence of other possible primary lesions strongly suggested the esophagus origin.

Background—Monoclonal precancerous cells undergo successive biochemical and genetic changes during the multistep process of carcinogenesis in the gastrointestinal tract. Despite a high association with intestinal-type stomach cancer (differentiated adenocarcinoma of the stomach), the role of intestinal metaplasia is unclear in stomach carcinogenesis.Aims—To study the clonality of intestinal metaplasia.Methods—The clonality of 86 single intestinal metaplastic glands isolated by EDTA treatment from gastrectomy specimens from patients with cancer were investigated. The methylation sensitive restriction enzyme HpaII and polymerase chain reaction (PCR) were used to detect a polymorphic human androgen receptor gene locus linked to an inactive X chromosome.Results—Forty one (48%) intestinal metaplastic glands were heterotypic (mixed cells of different allelic methylation) and 45 (52%) were homotypic (cell population of the same allelic methylation), while almost all the single pyloric glands were homotypic. Eleven of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands that had originated from different cells. There were no strong relationships between clonal type and location or histological type of intestinal metaplasia.Conclusion—Intestinal metaplasia in general is not a lesion that arises or proceeds monoclonally.

BACKGROUND: The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study, to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at different depths of invasion for component cancer cell types.METHODS: Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between the phenotypic type of cancer and their depth of invasion was evaluated.RESULTS: The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive disease from 23.5% to 31.1% ( P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the mucosa ( P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa, but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion.CONCLUSIONS: A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers. Intestinalization may occur independently in cancerous and noncancerous gastric mucosa.

An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

Although it has been demonstrated that acromegalic patients have an increased risk of neoplasms, especially colon neoplasms, gastric cancer with acromegaly is very rare--only five cases have been reported to date in Japan. We report here a rare case of gastric cancer with acromegaly in a 58-year-old woman, whose acromegalic change began at age 44. This patient showed typical clinical features of acromegaly, with increased concentrations of blood growth hormone (GH) and insulin-like growth factor I (IGF-I); she had four types of neoplasms; gastric cancer, colon tubular adenoma with moderate atypia, pancreatic mucinous cystadenoma, and subcutaneous lipoma. The gastric cancer was macroscopically 0-IIc type, 3.0 x 2.5 cm in size, and histologically diagnosed as a poorly differentiated adenocarcinoma with limited invasion of the mucosal layer. The previously documented stimulatory effects of GH and/or IGF-I on tumorigenesis and cell proliferation may have been responsible for the development of the multiple neoplasms in our patient.

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckel's diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckel's diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckel's diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.

1985年1月から95年11月までに当科で治療された直腸表面型早期癌41例 (m癌20病変, sm癌21病変) の治療方法, 臨床病理学的特徴, 治療成績を検討した.m癌の内視鏡切除術の適応は直径20mm以下で, 断端陽性, 合併症は見られなかった.深達度smの表面型早期癌は浸潤傾向の強い癌で, 52.4%が脈管侵襲を伴っていた.Type Bのelevated type with depressionは, 全例が脈管侵襲陽性で, D2以上の郭清をともなった手術が必要で, 肛門縁から5cmの距離があれば仙骨腹仙骨式超低位直腸切除術のよい適応である.それ以外のRbの表面型早期癌では, 術前の深達度診断に合わせて, 直腸傍リンパ節のみの郭清を直視下に行う仙骨式楔状切除術, 環状切除術を最終治療手段として行うことによって, 再発なく肛門機能温存が可能と考えられた.下部直腸表面型早期癌に対しては, 内視鏡治療と通常郭清手術の問に, 直腸傍リンパ節の郭清を行う後方アプローチを位置づけることが妥当である.

Postoperative pulmonary embolism (PPE) is a rare but extremely important complication because it is often lethal. We here report on two patients with PPE, both of who complained of an abdominal pain. Patient 1: A 60-year-old man who underwent a distal gastrectomy for an advanced gastric cancer complained of an abdominal pain and dyspnea and then fell into a state of cardiopulmonary arrest when he was walking on the second postoperative day. He was successfully resuscitated and the cause was diagnosed as PPE after examination. He eventually developed multiple organ failure and expired on the 23rd postoperative day notwithstanding full intensive care including anticoagulant therapy. Patinet 2: A 59-year-old man who underwent a distal gastrectomy for an early gastric cancer suddenly had an abdominal pain and collapsed on the first day after the operation. PPE was suspected by clinical symptoms and findings of some examinations. After the diagnosis of PPE was confirmed by a perfusion lung scintigraphy, the patient received an anticoagulant therapy and successfully recovered. We have fully realized that the prophylaxis of PPE is indispensable, and are now utilizing intermittent sequential pneumatic compression to prevent PPE.

Innervation of the gastric mucosa plays an important role in its defense mechanism. In a previous study, gastrectomy with denervation promoted tumorigenesis in the gastric body in rats after administration of a carcinogenic agent. In this study we investigated the induced gastric mucosal changes from the viewpoint of mucin histochemistry. Gastrectomy with denervation promoted the development of intestinal metaplasia, dysplasia, and carcinoma in the gastric body. Proliferating cell nuclear antigen labeling indexes as a marker for cell kinetics were significantly elevated in the denervated group. Analysis of mucin histochemistry by staining with paradoxical concanavalin A (PCA) and galactose oxidase-Schiff (GOS), which are markers for expression of the gastric phenotype, revealed that these mucins were positive in submucosal adenocystic proliferation and carcinoma at the anastomotic site. Conversely, in the gastric body these mucins disappeared with progression of dysplasia, and carcinoma cells contained neither PCA- nor GOS-positive mucins. These results suggest that there are two different processes of carcinogenesis in the gastric remnant, depending on the location, and that denervation of the remnant gastric mucosa promotes the development of cancer-related lesions in the gastric body.

Gastric atrophy is one of the important pathological states that cause gastric cancer. As atrophic gastritis is related to the risk of gastric cancer, it is important to diagnose atrophic gastritis. In the present study, we tried to establish endoscopic criteria for atrophic gastritis.A multicenter study of prospectively collected patients was conducted in 24 participating facilities. Two hundred and seventy-five patients received endoscopic examination and 15 endoscopic features, including diffuse redness, swelling of areae gastrica, and mucosal swelling, were evaluated. Biopsy specimens were taken from five points recommended by the Updated Sydney System, and evaluated by a single pathologist for atrophy. Sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve (AUC/ROC) of each endoscopic finding to histological atrophy were calculated. Pepsinogen I/II ratios of these patients were measured and compared to the endoscopic features.There was no single endoscopic feature that is highly specific for histological atrophy. In the corpus, the combination of visibility of vascular pattern and swelling of areae gastrica by indigocarmine chromoendoscopy showed the highest AUC/ROC (0.83). In the antrum, the combination of visibility of vascular pattern and mucosal swelling showed the highest AUC/ROC (0.70). These endoscopic findings correlated very well to the pepsinogen I/II ratio.Combination of endoscopic findings can improve diagnostic accuracy, and endoscopic diagnosis of atrophy is improved especially with new endoscopic criteria, such as swelling of areae gastrica or mucosal swelling.

In order to understand the histogenesis of precancerous and cancerous lesions, we investigated the clonality of normal single fundic gland and single pyloric gland using X-chromosome inactivation. Sixty percent of single fundic glands were cell populations methylated at the same alleles of the X-chromosome (homotypic) and 40% consisted of mixed cells methylated at different alleles of the X-chromosome (heterotypic). Among 28 fundic glands in which the clonality of the upper parts and that of the lower parts were analyzed separately, 11 glands were heterotypic in either part and 4 glands were homotypic with different allelic methylation in the upper part and in the lower part. Ninety-six percent of the single pyloric glands were homotypic and 4% were heterotypic. The results show the differences in the development of the fundic glands and the pyloric glands.

Background. Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. Methods. Using male Wistar rats, four groups of Billroth I(B-I) gastrectomy, Billroth II(B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. Results. The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS-AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. Conclusions. After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer. Cancer 1995 ; 75 :1490-6.

Spasmolytic polypeptide/trefoil family factor 2 expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We now have sought to determine whether hepatocyte growth factor (HGF) influences the development of SPEM and oxyntic atrophy. DMP-777, a parietal cell ablating reagent, was administered to HGF activator (HGFA)-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed in the DMP-777 treatment phase and recovery phase. Both wild-type and HGFA knockout mice showed SPEM, and there was no difference in SPEM development. However, after cessation of DMP-777, HGFA-deficient mice showed delayed recovery from SPEM compared with wild-type mice. Foveolar cell hyperplasia and the increase in proliferating cells after parietal cell loss were reduced in HGFA-deficient mice. The HGFA does not affect emergence of SPEM. However, the absence of HGFA signaling causes a delay in the recovery from SPEM to normal glandular composition. HGFA also promotes foveolar cell hyperplasia and mucosal cell proliferation in acute oxyntic injury.

Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation.In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy.The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group.L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo.

Gastritis is an important pathological state that causes gastric atrophy and cancer. The Sydney System is a well-used classification for histological evaluation for gastritis. However, there is no concordance with endoscopic findings. In the present study, we tried to establish endoscopic criteria and diagnosis for the inflammation activity of gastric mucosa.A prospective multicenter study was conducted and 24 facilities participated. Two hundred and seventy patients received endoscopic examinations and 15 endoscopic features were evaluated. Biopsy specimens were taken from five points, and evaluated by a single pathologist for mononuclear cell infiltration and polymorphonuclear cell infiltration. Sensitivity, specificity, positive predictive value, negative predictive value, area under curve of receiver operating characteristics (AUC/ROC) of each endoscopic finding to histological gastritis were calculated.There was no single endoscopic finding that was highly specific for mononuclear cell infiltration and polymorphonuclear cell infiltration. In the corpus, the combination of swelling of areae gastrica by the indigo carmine contrast method (IC method) and lack of a regular arrangement of collecting venules (RAC) in angle for mononuclear cell infiltration (0.887), and the combination of swelling of areae gastrica by the IC method and diffuse redness for polymorphonuclear cell infiltration (0.851) showed the highest AUC/ROC. In the antrum, the combination of diffuse redness and visibility of a vascular pattern for mononuclear cell infiltration (0.780), and the combination of visibility of vascular pattern and swelling of areae gastrica by the IC method for polymorphonuclear cell infiltration (0.795) showed the highest AUC/ROC.Combination of endoscopic findings can improve diagnostic accuracy, and sensitivity of examination for inflammation.

Technique in laparoscopic surgery using long forceps, laparoscopic coagulating shears (LCS, vessel sealing systems, and so on is absolutely different from that in open surgery. The mobility of long forceps used through ports placed at the abdominal wall is limited, and so training is required at a “dry” laboratory before addressing clinical cases. Training in an animal laboratory is much better than that in a dry laboratory, but it is often difficult to access an animal laboratory. It would be ideal to have a dry laboratory in the institution, so any young doctor can access it at any time. Everyone could then be familiar with the items used for laparoscopic surgery and hone skills of required techniques such as ligation.

The lesser sac is a potential space behind the stomach. The peritoneal covering can be traced from the anterior surface of the pancreas to the spleen. The two landmark folds are important for laparoscopic gastrectomy. The pancreaticogastric fold, which normally is covered by the left lobe of the liver, contains the left gastric artery from the retroperitoneal space to the lesser curvature of the stomach.

Peppermint oil has been shown to relax gastrointestinal smooth muscle. In this randomized, placebo-controlled study, an L-menthol preparation, NPO-11, was assessed for tolerability and pharmacokinetics (PK) during gastrointestinal endoscopy. Single doses of NPO-11, as high as 320 mg, were well tolerated. NPO-11 was rapidly absorbed, with peak concentrations reached within 1 h after administration. Approximately 70% of the administered L-menthol and its metabolites were excreted in the urine, and this amount fluctuated with no change in the dose. The principal metabolite identified in plasma and urine was menthol glucuronide. The other metabolites include mono- or di-hydroxylated menthol derivatives, most of which are excreted, in part, as glucuronic acid conjugates. The pharmacokinetic data indicated that when NPO-11 is sprayed directly onto the gastric mucosa, it is rapidly metabolized to glucuronic acid conjugates that are excreted in urine. The findings from this study provide new data on the safety and PK of NPO-11 and support further trials.

A Bochodalek hernia is rarely seen in adults. An 18-year-old man was referred to our institute with the chief complaint of a sudden onset of left subcostal pain, nausea, and vomiting. A radiograph and a computed tomographic scan of the chest revealed a Bochodalek hernia. Emergency surgery was thus performed. The herniated organs were put back into the peritoneal cavity and the hernial hilum was closed. The postoperative course was uneventful. A routine chest radiograph 1 month before had shown a slight elevation of the left hemidiaphragm and further examination using computed tomography suggested a Bochodalek hernia, but he had merely been followed up since there were no symptoms. As soon as a diagnosis is made, specific repairs should be carried out even if no symptoms are present, to prevent such complications as strangulation or perforation.

Accurate image analysis is essential for correct diagnosis in gastrointestinal endoscopy. In the past, the process of diagnosis has varied based merely on the personal experience of the examiner, and yet there has been no basic study concerning its improvement. We conducted a basic study on endoscopic image analysis particularly with regard to eye fixation points, and noticed that there was a significant difference between beginners and experts. The beginners tended to fix their eyes on the area showing a larger color tone difference, whereas the experts tended to have their fixation points on areas with less of a color tone difference

We conducted an experimental study of the morphological changes in gastric mucosa following vagotomy, in particular of the chronic effects of duodenogastric reflux. Male Wistar rats were divided into four groups: sham operation, duodenogastric reflux (DGR), truncal vagotomy with duodenogastric reflux (TV + DGR), and truncal vagotomy with bypass (TV + bypass). The last operation was performed to observe the effects of vagotomy without reflux. The duodenogastric reflux procedure was established by cutting the duodenum just distal to the orifice of bile and pancreatic ducts following gastrojejunostomy. After 12 and 30 weeks, animals were killed for morphological studies of gastric mucosa. The TV + DGR group showed formation of multiple elevated lesions macroscopically, and microscopically showed marked atrophy of gastric glands and proliferation of cystically dilated adenomatous lesions, which were regarded as precancerous or paracancerous lesions. The DGR group showed chronic gastric ulcer and hyperplasia of the gastric glands. However, the TV + bypass group showed no remarkable changes in the gastric mucosa. These results indicate that chronic effects of duodenogastric reflux following vagotomy induce severe inflammatory changes as well as structural alteration of the gastric mucosa. Therefore, a regular follow-up observation is necessary after vagotomy when combined with a drainage procedure because the latter could promote duodenogastric reflux and produces pathological changes to the stomach.

胃全摘術後の膵内分泌能の変化とそれに伴う耐糖能障害・栄養障害の関係を調べる目的で, 術前患者 (A群) ・胃全摘膵合併切除患者 (B群) ・胃全摘膵温存患者 (C群) の3群に対し経静脈性糖負荷試験を行い, 膵内分泌能を調べた.その結果, K値 (mg/dl.min) はA群1, 27±0.19, B群0.76±0.2, C群0.71±0.28, T.I.I (μIU.dl/ml.mg) はA群0.18±0.1, B群0.01±0.05, C群0.04±0.01であり, B群のみならずC群でも耐糖能障害やインスリン分泌能の低下がみられた.しかしB・C群間ではHbA1, HbA1C以外あまり差がなく, 膵合併切除の不利益ははっきりしなかった.術後の耐糖能障害の指標としてHbA1, HbA1Cが, 栄養障害の指標としてBMI, 体重比%がきわめて有用で, インスリン分泌能の指標にもなりえた.また糖尿病患者では胃全摘後栄養障害が顕著となるため, Interposition再建や膵温存による胃全摘術が望まれる.

This study assesses the surgical stress of laparoscopic adrenalectomy (LA) in patients with pheochromocytoma using catecholamine and cytokine. The study was conducted on one patient who had laparoscopic adrenalectomy performed for pheochromocytoma, and three patients as controls who had undergone laparoscopic cholecystectomy (LC) for cholecystolithiasis. Catecholamines, tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were measured at 30-minute intervals intraoperatively, and on the first, third and fifth postoperative days (POD) respectively. Plasma TNFalpha and IL-6 were measured by a commercially available sandwich enzyme-linked immunosorbent assay test. During the operation. changes of catecholamine concentration in LA were far larger than those in LC. The changes of TNFalpha concentration in LA were also larger than those in LC. TNFalpha returned to basal value at the end of the operation in LC, but it did not in LA. TNFalpha concentration in LC changed a little after the surgery, whereas that in LA sharply increased and was maintained at a high level from 1 POD until 5 POD. Enhanced cytokine responses were observed in LA compared to LC during and after the surgery. We concluded that laparoscopic adrenalectomy may give those patients with pheochromocytoma more surgical stress than laparoscopic cholecystectomy for cholecystolithiasis, during and after the operation.

Summary Background Analyses of microRNA expression profiles have shown that many microRNAs are expressed aberrantly and correlate with tumorigenesis, progression, and prognosis of various haematological and solid tumours. We aimed to assess the relation between microRNA expression and progression and prognosis of gastric cancer. Methods 353 gastric samples from two independent subsets of patients from Japan were analysed by microRNA microarray. MicroRNA expression patterns were compared between non-tumour mucosa and cancer samples, graded by diffuse and intestinal histological types and by progression-related factors (eg, depth of invasion, metastasis, and stage). Disease outcome was calculated by multivariable regression analysis to establish whether microRNAs are independent prognostic factors. Findings In 160 paired samples of non-tumour mucosa and cancer, 22 microRNAs were upregulated and 13 were downregulated in gastric cancer; 292 (83%) samples were distinguished correctly by this signature. The two histological subtypes of gastric cancer showed different microRNA signatures: eight microRNAs were upregulated in diffuse-type and four in intestinal-type cancer. In the progression-related signature, miR-125b, miR-199a, and miR-100 were the most important microRNAs involved. Low expression of let-7g (hazard ratio 2·6 [95% CI 1·3–4·9]) and miR-433 (2·1 [1·1–3·9]) and high expression of miR-214 (2·4 [1·2–4·5]) were associated with unfavourable outcome in overall survival independent of clinical covariates, including depth of invasion, lymph-node metastasis, and stage. Interpretation MicroRNAs are expressed differentially in gastric cancers, and histological subtypes are characterised by specific microRNA signatures. Unique microRNAs are associated with progression and prognosis of gastric cancer. Funding National Cancer Institute.

BACKGROUND: Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae. METHODS: Genes that are silenced in human ESCCs were searched for by treating 3 ESCC cell lines with the demethylating agent, 5-aza-2′-deoxycytidine and performing oligonucleotide microarrays. Methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction analysis of 60 ESCCs and their corresponding background mucosae. RESULTS: Forty-seven genes were identified as methylation-silenced in at least 1 of the 3 ESCC cell lines, and 14 of those genes (claudin 6 [CLDN6]; G protein-coupled receptor 158 [GPR158]; homeobox A9 [HOXA9]; metallothionein 1M [MT1M]; neurofilament, heavy polypeptide 200 kDa [NEFH]; plakophilin 1 [PKP1]; protein phosphatase 1, regulatory [inhibitor] subunit 14A [PPP1R14A]; pyrin domain and caspase recruitment domain containing [PYCARD]; R-spondin family, member 4 [RSPO4]; testis-specific protein, Y-encoded–like 5 [TSPYL5]; ubiquitin carboxyl-terminal esterase L1 [UCHL1]; zinc-finger protein 42 homolog [ZFP42]; zinc-finger protein interacting with K protein 1 homolog [ZIK1]; and zinc-finger and SCAN domain containing 18 [ZSCAN18]) were used as markers. In the background mucosae, methylation levels of 5 genes (HOXA9, MT1M, NEFH, RSPO4, and UCHL1) had significant correlations with smoking duration (ρ = .268; P = .044; ρ = .405; P = .002; ρ = .285; P = .032; ρ = .300; P = .024; and ρ = .437; P = .001, respectively). In contrast, an inverse correlation between PYCARD methylation levels and alcohol intake was observed (ρ = −.334, P = .025) among individuals with the inactive aldehyde dehydrogenase 2 (ALDH2) genotype. CONCLUSIONS: The current results suggested that ESCCs developed from an epigenetic field for cancerization, which was induced by exposure to carcinogenic factors, such as tobacco smoking. The epigenetic field defect will be a novel target for risk diagnosis and prevention of ESCCs. Cancer 2009. © 2009 American Cancer Society.

In 2005, a Japanese epidemiological study showed that increase in plasma glucose levels is a risk factor for gastric cancer. However, no animal model has hitherto shown any association between diabetes mellitus and neoplasia in the stomach. Diabetic (db/db) mice have obese and diabetic phenotypes, including hyperglycemia, because of disruption of the leptin receptor. In the present study, effects of hyperglycemia and/or hyperinsulinemia on the development of proliferative lesions were therefore examined in db/db mice given N-methyl-N-nitrosourea (MNU). A total of 120 mice were assigned to four groups: Group A, 40 db/db mice with MNU; Group B, 40 + /db mice with MNU; Group C, 30 misty (wild-type) mice with MNU; Group D, 10 db/db mice without MNU. MNU was given at 60 ppm in drinking water for 20 weeks. Subgroups of animals were sacrificed at weeks 21 and 30 and blood samples were collected to measure glucose, insulin, leptin, and adiponectin concentrations. The removed stomachs were fixed in formalin, and embedded in paraffin for histological examination and immunohistochemistry. At week 30 in Groups A, B, C and D, hyperplasia was observed in 100, 79, 57, and 0%, and dysplasia in 91, 43, 71, and 0%, respectively. Adenocarcinomas and pepsinogen-altered pyloric glands (PAPG), putative preneoplastic lesions, were observed only in Group A, at an incidence of 45%. The serum levels of insulin and leptin were also elevated in Group A. Gastric carcinogenesis by MNU was enhanced in db/db mice, possibly in association with hyperinsulinemia and hyperleptinemia.

To investigate the phenomenon of remnant gastric motility and emptying after local resection.Fifteen dogs were divided into three groups: a control (CONT) group, a group that underwent local resection of the greater (GREAT) curvature, and a group that underwent resection of the lesser (LESS) curvature. We conducted a strain gauge force transducer study, a [(13)C]octanoic acid breath test ((13)C-OBT), and a mosapride citrate effect test. Based on these results, we worked out the receptive relaxation (RR), motility index (MI), and postprandial period (PP) in the postprandial state, and the frequency, duration, and MI of phase III in the fasted state. The half emptying time (T (1/2)) of (13)C-OBT was also calculated. The MI was compared according to the mosapride effect test results.Postprandial RR, antro-pyloro-duodenal coordination, and fasting contractions were maintained in all three groups. Receptive relaxation was significantly shorter in the LESS group than in the other groups. Motility index was significantly lower in both treatment groups than in the CONT group. The PP was significantly longer in the GREAT group than in the other two groups. The (13)CO(2) excretion curves did not differ significantly among the groups. The duration of phase III was remarkably less in the treatment groups than in the CONT group, and MI was significantly lower in the LESS group than in the other groups in the fasted state. The MI increased remarkably after mosapride administration in the CONT group, showing no differences in other objective groups.Gastric function was maintained after gastric local resection, although its motility decreased.

This case report describes a three-year survivor case by weekly paclitaxel, who had peritoneal dissemination of gastric cancer resistant to methotrexate and 5-fluorouracil therapy. A 62-year-old female with massive ascites, abdominal pain, and difficulty in eating received a weekly paclitaxel schedule which consisted of a 1-hour infusion of paclitaxel (70 mg/m(2)) given once a week for three weeks followed by a 1-week rest, repeated every four weeks. Short course premedication was given 30 minutes prior to paclitaxel. The administrations could be performed on an outpatient basis with transient grade 3 neutropenia requiring no specific medication. Neither hypersensitivity reactions nor peripheral neuropathy developed. A dramatic disappearance of ascites and relief of abdominal pain, as well as a rapid recovery of food intake enabled the patient to be withdrawn from nutritional support through central venous catheter, indicating this schedule's contribution to improve her quality of life. A three-year survival from the commencement of weekly paclitaxel without evidence of relapse was confirmed. Weekly paclitaxel was based on the dose-dense concept, where cumulative paclitaxel exposures by frequent, repetitive administration have a more potent antitumor effect than higher dose 21-day schedule. Encouraging aspects in the weekly paclitaxel schedule in this report are that the survival time is considered to be satisfactorily long as compared with those of other case reports in the literature achieved by a convenient outpatient use with acceptable toxicities, leading to a comprehensive contribution to improve patient quality of life.

Neuroendocrine tumors (NETs) are relatively rare and comprise carcinoids, gastrinomas, and poorly differentiated endocrine carcinomas (PDECs). Diagnostic procedures should include endoscopy with biopsy, computed tomography, or magnetic resonance imaging. Fluorodeoxyglucose positron-emission tomography is also useful for the detection of extraabdominal metastases. Complete resection with lymph node dissection, as recommended for other cancers, such as distal gastrectomy, total gastrectomy, and pancreaticoduodenectomy, should be attempted in localized NETs. Endoscopic submucosal dissection should also be attempted in early-stage disease. Both curative and palliative surgery is indicated for patients with liver metastases of foregut-origin NETs. Combination chemotherapy (cisplatin/carboplatin + etoposide) may be useful in treating PDECs with metastases. Combination therapies with streptozotocin, doxorubicin, and 5-fluorouracil are also useful for the treatment of carcinoid tumors. Somatostatin analogues, such as octreotide and SOM 230, have been registered for the control of hormonal symptoms in patients with gastrointestinal NETs.

IRAK-4 plays an essential role in Toll-like receptor (TLR)/IL-1 receptor signaling. However, its signaling and regulation mechanisms have remained elusive. We have reported previously that stimulation of TLR2, TLR4 or TLR9, but not TLR3, leads to downregulation of IRAK-4 protein. Here, we show that expression of MyD88 leads to downregulation of endogenous as well as exogenously expressed IRAK-4 protein in HEK293 cells. Expression of TRIF did not cause IRAK-4 downregulation although it induced NF-kappaB activation. Expression of either a deletion mutant of MyD88 lacking its death domain or MyD88s, neither of which induced NF-kappaB activation, did not lead to IRAK-4 downregulation. MyD88-induced downregulation was observed in an IRAK-4 mutant lacking the kinase domain, but not in another mutant lacking the death domain. These results demonstrate that downregulation of IRAK-4 requires activation of the MyD88-dependent pathway and that the death domains of both MyD88 and IRAK-4 are important for this downregulation.

Subtotal gastrectomy with lymphadenectomy including Group 2 lymph nodes, D2 lymphadenectomy, has been performed in Japan as a standard surgical treatment for gastric cancer regardless of its stage, and good survival rates have been obtained. However, retrospective analysis of the results revealed that about 80% of early cancers have no lymph node involvement, suggesting curative treatment of these early cancers without the standard D2 lymphadenectomy; they may be curative with limited surgery. Limited surgery includes two limitations, the scope of the gastrectomy and lymphadenectomy. In terms of quality of life (QOL) after gastric surgery, preservation of the gastric function and less invasive surgery are desirable. In this section, we discuss indications and results of limited surgery for early gastric cancer. Furthermore, application of a newly developed surgical treatment will be proposed.

An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P

A pylorus-preserving gastrectomy (PPG) is a procedure for gastric cancer (GC) patients which attempts to control gastric emptying and to minimize postoperative nutritional disadvantages. The persistence of conflicting stances concerning qualifying candidates for PPG--a narrower or wider segment of patients--is attributable to a lack of decisive evidence concerning the precise nutritional impact of suprapyloric lymph node clearance.Forty-eight patients underwent a PPG with (30 patients; dissection group) or without (18 patients; preservation group) suprapyloric lymph node clearance between 2002 and 2004. Patients with mucosal GC located in the middle third of the stomach were assigned to the preservation group and the other early GC patients formed the dissection group. Those who were followed up more than one year postoperatively were selected from the preservation (8 patients) and the dissection (16 patients) groups, and changes in body weight, hemoglobin, total protein, and albumin were compared between the two groups. Baseline clinicopathological characteristics, surgically related events, and supportive medications were also compared between the two groups.Dissection group patients received significantly longer surgery (p0.01) and a wider scope of lymphadenectomy (p0.0001) than preservation group patients. Other factors including the length of postoperative hospital stay and morbidity rate did not differ between the two groups. Percent changes in body weight, hemoglobin, total protein, and albumin, as well as postoperative profiles of each parameter were similar between the two groups.These results suggest that suprapyloric lymph node clearance resulted in more traumatic surgery while it did not exacerbate postoperative nutritional status as compared with suprapyloric lymph node preservation. PPG is justifiable for submucosal GC or an even wider segment of patients by suprapyloric lymph node clearance without nullifying the anticipated nutritional benefit.