Objective: To improve the understanding of the etiology of perforated peptic ulcers (PPUs) and their association with cancer development.

Introduction: Some patients are more susceptible to multiple primary malignancies (MPMs). However, understanding of the effects of this susceptibility on the benefits and detriments to patient survival are poorly understood.

Introduction: Whether good baseline quality of life (QOL) is linked to improved QOL: improved overall survival (OS) which is relevant to HLA-restricted peptides has not been evaluated, and the causal nature of this correlation is not known.

Introduction: Whether human leukocyte antigens (HLAs) and human endogenous retroviruses (HERVs) affect therapeutic outcomes is unknown. Here, we focused on the similarity between HERV and human immunodeficiency virus (HIV) genes.

Background and Purpose: Based on the homogenous human leukocyte antigen (HLA) properties of the Japanese population, patients who have undergone examination of their HLA antigens have exhibited more beneficial outcomes than those without HLA examination. This study aimed to evaluate whether HLA type and location of the institutes and hospitals where patients were enrolled affected patient outcomes. Materials and Methods: A total of 1753 patients from member hospitals of the Japanese Society of Strategies for Cancer Research and Therapy throughout Japan were enrolled in this study from August 1977 to August 2005. HLA antigens were serologically tested using the NIH standard microlymphocytotoxicity method for HLA-A, -B, -C, - DR and -DQ. We used a method of quantification for the response pattern and classified similar HLA antigens into four groups: type 1, 2, 3 or 4, and classified patients into four groups: patients who received effective therapy, ineffective therapy, or neither effective nor ineffective therapy, and unclassified. Effective therapy was defined as therapy that resulted in a patient's survival for a period of at least 5 to 10 years, and ineffective therapy as a therapy that resulted in a patient's survival for a period of less than 5 years. The location of the institutes and hospitals where patients were enrolled was classified into three groups: eastern Japan, western Japan and Tokai University. Conclusions: There were no significant differences among HLA types, the locations and patient outcomes. Our idea is promising as a path toward individual treatment. HLA information could provide personalized therapy based on the homogenous HLA properties of the Japanese population.

Prominent lymphocytic infiltration and lymphoid follicles surrounding tumor cells are extremely rare findings in esophageal carcinoma. We report on the endoscopic, histological, and immunohistochemical features of a rare case of squamous cell carcinoma of the esophagus with lymphoid stroma. A 59-year-old woman was diagnosed with type 0-Is superficial esophageal carcinoma and underwent radical esophagectomy with lymph node dissection. Macroscopically, the tumor was protruding, and was covered with normal epithelium resembling a submucosal tumor. Histopathological examination demonstrated that the esophageal lesion was classified as a poorly differentiated squamous cell carcinoma with lymphoid stroma, extending to the deep submucosa (SM3) with lymph node metastasis (T1b, N2, M0, stage II). Epstein-Barr virus infection was ruled out by immunohistochemical and in situ hybridization analyses. Infiltrating B-lymphocytes were observed forming lymphoid follicles adjacent to carcinoma cell nests, and numerous T lymphocytes were widely spread throughout the specimen, as well as distributed in the marginal zone of the lymphoid follicles. Prominent human leukocyte antigen DR region (HLA-DR) immunoreactivity was noted in most carcinoma cells and focally infiltrating B cells in the lymphoid follicles, and these observations were thought to be due to activation of immunological interactions between carcinoma cells positive for HLA-DR and host lymphocytes.

We report a case of early esophageal carcinomas associated with achalasia treated by endoscopic submucosal dissection. A 46-year-old man was diagnosed of esophageal achalasia, flask type and Grade II in 2001, and had been treated by pneumatic dilatation for symptomatic achalasia conservatively. The patient was operated by Tokai University method, Heller's long esophagomyectomy, Hill's posterior cardiopexy, fundoplication and selective proximal vagotomy using a laparotomy in August 2009. One year and three months after the operation, two lesions of early carcinomas of type 0-IIb and 0-IIc, each 1cm in size, were detected in the middle thoracic esophagus, and treated by endoscopic submucosal dissection. Pathological examination of the each lesion revealed proliferation of squamous cell carcinoma in situ (T1a-EP). The entire esophageal mucosa around the carcinoma demonstrated hyperplastic changes of stratified squamous epithelium and foci of intraepithelial neoplasia. In the patient of achalasia, food stasis in esophagus is thought to induce chronic hyperplastic esophagitis, converting eventually to malignant transformation. Achalasia is known as a risk factor of esophageal squamous cell carcinoma. Careful long-term follow-up for patients of achalasia by endoscopic screening is recommended, even if after treatment by pneumatic dilatation or operation for achalasia.

Background: The question in the title remains unanswered and also is both old and new among gastric surgeons. Although there have been many reports about the early-stage quality of life and postoperative morbidity, they have failed to conclude about the advantages of these two reconstructions after distal gastrectomy. In this study, we summarized more than 30 years of experience and evaluated whether the Billroth I or Billroth II reconstruction procedure is better for patient survival after distal gastrectomy.Methods: From January 1977 to August 2005, a total of 1410 gastric cancer patients underwent distal gastrectomy with Billroth I (n=1184) or Billroth II (n=226) reconstruction in the Department of Gastroenterological Surgery, Tokai University. The 10- and 20-year follow-up cases numbered 980 (82.8%) and 692 (58.4%) for Billroth I, and 213 (94.2%) and 195 (86.3%) for Billroth II as of September 2009, respectively. Among them, 1015 patients (72.0%) received curative resection and were followed to evaluate the types of recurrence.Results: In the patients with Billroth I and Billroth II, the 5-, 10-, 15-, and 20-year survival rates were 77.4%, 66.6%, 56.0%, and 45.7%, and 39.7%, 32.8%, 25.9%, and 19.6%, respectively (P<0.0001; relative risk, 2.683; 95% confidence interval, 2.261?3.183). The patients in stages 1A and 4 showed significantly better survival with Billroth I than with Billroth II. The patients with Billroth II (10/86, 11.6%) showed significantly higher hematogenous recurrence than those with Billroth I (41/929, 4.4%).Conclusions: If gastric cancer patients must receive distal gastrectomy, we recommend they receive Billroth I reconstruction.

The 5-year relapse-free survival rate (5Y-RFS) and the 5-year overall survival rate (5Y-OS) were calculated for 972 patients (stage I, 206 patients; stage II, 396 patients; stage III, 370 patients). We divided the stage III group into 259 patients with IIIa/N1 disease (≤3 positive nodes) and 111 patients with IIIb/N2 disease (≥4 positive nodes) according to the Japanese classification. The IIIa/N1 and IIIb/N2 categories were each subdivided into T1/2 (stage IIIa, 45 cases; IIIb, 9 cases) and ≥T3 (stage IIIa, 214 cases; IIIb, 102 cases) according to the TNM classification, and 5Y-RFS and 5Y-OS were compared between each subcategory and each group. The 5Y-RFS/5Y-OS values calculated for each stage were as follows: stage I, 94.0/90.7%; stage II, 80.5/81.1%; stage III, 63.5/65.7%. When stage IIIa was compared with IIIb, we obtained 67.9/72.0% for stage IIIa and 53.6% (p=0.001)/50.4% (p<0.001) for stage IIIb. For stage IIIa vs. IIIb in the ≥T3 category, we obtained 63.1/68.5% for stage IIIa and 51.9% (p=0.010)/49.0% (p=0.008) for stage IIIb. For stage IIIa vs. IIIb in the T1/2 category, we obtained 92.1/92.0% for stage IIIa and 72.9% (p=0.040)/63.5% (p=0.003) for stage IIIb. There were significant differences between T1/2 and ≥T3 within stage IIIa (p=0.001/p=0.009), but not within stage IIIb. These results suggest that the T1/2N1 category of colorectal cancer should be classified as a subcategory of stage IB/Ib rather than stage IIIA (TNM)/IIIa (Japanese classification).

OBJECTIVE:To develope a new procedure for laparoscopic exogastric resection using a so-called "fundic rotation technique (FRT)" for gastric submucosal tumors (SMTs) on the posterior wall near the esophagogastric junction (EGJ).METHODS:Between April 2006 and February 2010, we performed laparoscopic resection for SMTs located near the EGJ (within 3.0 cm from the EGJ) in ten consecutive patients. Out of seven exogastric resections, an FRT was used in five patients with posterior tumors near the EGJ.RESULTS:The patients comprised three men and two women, with an average age of 65 years. The maximum tumor diameter averaged 3.8 cm (range, 2.0-8.0 cm), and the average distance from the EGJ was 1.5 cm (range, 0-2.5 cm). The pathological diagnosis was GIST in all cases. One case was converted to an open surgery due to its large size (8.0 cm) and the difficult access. All the patients quickly returned to their normal activities. No patient complained any symptoms of regurgitation, and endoscopic examination revealed no remarkable reflux esophagitis. No tumor recurrences occurred during a median follow-up period of 30 months.CONCLUSION:The indications for laparoscopic resection of SMTs located near the EGJ may be extended using an FRT.

Pancreatic endocrine tumors (PETs) rarely involve the main pancreatic duct. We report a case of malignant nonfunctioning pancreatic endocrine tumor (NFPET) with prevalent intraductal growth. A 47-year-old woman was referred to us after ultrasonography at a routine health check showed diffuse swelling of the pancreas. Preoperative imaging showed a solid mass in the tail of the pancreas and a bulging intraductal mass in the main pancreatic duct. We performed total pancreatectomy because the tumor occupied almost the entire lumen of the main pancreatic duct. Histological examination confirmed well-differentiated endocrine carcinoma. We review reported cases of the intraductal growth of NFPETs and discuss the pathogenesis of these unusual tumors.

Lymph nodes from patients with colorectal cancer were immunohistochemically stained for cytokeratin to investigate the relationship between the presence of occult neoplastic cells (ONCs) and recurrence/metastasis. A total of 80 patients with stage III/Dukes' C colorectal cancer were divided into 16 patients who developed recurrence/metastasis (recurrence group) and 64 patients without recurrence (non-recurrence group). ONCs were compared between the two groups with respect to i) single cells (≥ 3 floating ONCs), ii) clusters of cells (1 or more floating aggregates of 2-20 ONCs) and iii) single cells + clusters. When single cells were detected, the sensitivity for recurrence was 87.5% (14/16, p = 0.002), the positive predictive value (PPV) was 32.6% (14/43), the specificity was 54.7% (35/64) and the negative predictive value (NPV) was 94.6% (35/37). For clusters, the sensitivity was 87.5% (14/16, p<0.001), PPV was 41.2% (14/34), specificity was 68.8% (44/64) and NPV 95.7% (44/46). With single cells + clusters, the values were 87.5% (14/16, p<0.001), 48.3% (14/29), 76.6% (49/64) and 96.1% (49/51), respectively. These results suggest that the detection of single cells + clusters is a sensitive indicator of a high risk of recurrence/ metastasis, while ONCs are useful for identifying the low-risk group of patients with stage III colorectal cancer.

Background:Our clinical data accumulated during 30 years of clinical practice at the Department of Gastroenterological Surgery, Tokai University, indicated the effectiveness of the Billroth 1 procedure that preserve duodenal food passage, as well as its suppressive effect on hepatic metastasis. Here, the effectiveness of food passage through the duodenum is examined via experiments using BALB/c mice. Methods:In the first phase, gastrojejunostomy was performed using BALB/c mice. In the second phase, by duodenum ligation or not, the non-duodenal passage and duodenal passage models, respectively, were created. Transplantable colon26 was transplanted into the spleen, and the number of hepatic metastases was examined. At the same time, Kupffer cells, NK cells, Th1 cytokines, and Th2 cytokines such as IL-12, INFγ, and IL-4 were measured in the sham operation mice. Results:(1) Hepatic metastasis was observed in 9 of 25 mice (36.0%) and 18 of 26 mice (69.2%) in the duodenum passage model and non-duodenum passage model, respectively (p = 0.017, RR = 4.000, 95%CI, 1.246-12.842), and the average numbers of metastasis were 0.76 and 3.12, respectively (p = 0.077). (2) No significant differences were observed in the number of Kupffer cells and NK activity, and the production of Th1 cytokines and Th2 cytokines between the two groups. Conclusion:It was considered that in non-duodenum passage reconstructive surgery that produced bacterial translocation due to the existence of a blind loop may have induced cytokine production, causing the activation of NK cells and leading eventually to hepatic metastasis.

OBJECTIVE:The aim of this study was to clarify the influence of histological changes in the gastric remnant on Helicobacter pylori (H. pylori) infection after distal gastrectomy (DG) and proximal gastrectomy (PG).METHODS:In total, 101 patients who underwent DG (n = 76) or PG (n = 25) for gastric cancer were included in the study. Three biopsy specimens from the remnant stomach were obtained during upper gastrointestinal endoscopy. Each specimen was scored according to the updated Sydney system for classifying gastritis and was examined for H. pylori infection.RESULTS:The H. pylori infection rate after DG was 60.5% while that after PG was 20.0% (P < 0.001). The histological score for neutrophils after DG was 60.5% while that after PG was 12.9% (P < 0.001). Intestinal metaplasia after PG was 76.0% while that after DG was 22.4% (P < 0.001). No differences in mononuclear cells or atrophy were observed between the two gastrectomy groups.CONCLUSIONS:H. pylori infection occurred more frequently after DG than after PG. Histological inflammation of the gastric remnant after DG was higher than that after PG. Intestinal metaplasia of the gastric remnant after PG was higher than that after DG. The intestinal metaplasia that induced inflammation indicated that H. pylori infection after PG was at a low level.

An annular pancreas is an uncommon congenital anomaly that usually presents early in childhood. Malignancy in the setting of an annular pancreas is unusual. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 59-year-old man presented with epigastric discomfort and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla of Vater. Preoperative imaging showed the pancreatic parenchyma encircling the descending duodenum and a tumor at the papilla of Vater. A pancreaticoduodenectomy was performed for the annular pancreas and the ampullary tumor. Histological examination confirmed a complete annular pancreas and carcinoma in situ of the papilla of Vater. We also provide a review of the reported cases of an annular pancreas with periampullary neoplasms and discuss the clinical characteristics of this anomaly.

This study examined quality of life (QOL) and illness perceptions in Dutch and Japanese patients with non-small-cell lung cancer, thereby extending the body of knowledge on cultural differences and psychosocial aspects of this illness. 24 Dutch and 22 Japanese patients with non-small-cell lung cancer filled out questionnaires on three occasions: immediately before chemotherapy, 1 week later, and 8 weeks after the initial chemotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assessed QOL, and the Brief Illness Perception Questionnaire (B-IPQ) illness perceptions. Scores on several QOL measures indicated (a) major impact of first chemotherapy sessions, and (b) some tendency to returning to baseline measures at 8 weeks. Differences between Japanese and Dutch samples were found on five EORTC QLQ-C30 dimensions: global health status, emotional functioning, social functioning, constipation, and financial difficulties, with the Dutch patients reporting more favorable scores. Regarding illness perceptions, Japanese patients had higher means on perceived treatment control and personal control, expressing a higher sense of belief in the success of medical treatment than Dutch patients. In both Japanese and Dutch patients, impact of chemotherapy on QOL was evident. Some differences in illness perceptions and QOL between the two samples were observed, with implications for integral medical management. Both samples reported illness perceptions that reflect the major consequences of non-small-cell lung cancer. Incorporating symptom reports, illness perceptions, and QOL into medical management may have positive consequences for patients with non-small-cell lung cancer.

症例は75歳，女性．心窩部不快感を主訴に上部消化管内視鏡検査を施行され，幽門狭窄を認めた．粘膜面に異常はなく幽門部に浮腫状狭窄を認めた．生検では，悪性像は認めなかった．腹部CT検査ではびまん性壁肥厚を認め，腫瘍マーカーはCA19-9値が735U/mlと高値であった．確定診断は得られなかったが，症状の改善を認めず，CA19-9が高値であり，胃壁の肥厚を認めることから，悪性の可能性を疑い手術を施行した．切除標本では壁の肥厚は認めず，狭窄部の硬化のみであった．病理診断では粘膜上皮に癌を認めず，粘膜下浸潤型の高分化型腺癌であった．免疫染色でCA19-9が陽性であり，術後に血清のCA19-9値は正常化したため，CA19-9産生胃癌と診断した．粘膜面に異常がなく，生検で悪性像が得られない幽門狭窄を認めた場合には癌の可能性も考慮すべきである．

BACKGROUND/AIMS:The morphological distribution of tumor cells in metastatic lymph nodes has been investigated in positive sentinel lymph nodes in several solid cancers. The aim of this study was to clarify the effect of the distribution of metastatic foci in lymph nodes on the prognosis in gastric cancer.METHODS:The distribution of metastatic foci in the 100 node-positive patients who had undergone curative gastrectomy were classified into two groups: (1) massive type, in which the tumor occupied the entire lymph node, and (2) non-massive type, in which the tumor did not occupy the entire lymph node.RESULTS:There were 38 patients in the massive type group and 62 patients in the non-massive type group. The 10-year survival rate was significantly poorer in the massive type group (p = 0.001). Multivariate analysis showed that distributional type and nodal status were independent prognostic factors. UICC N stage was subcategorized by distributional type, and survival was shown to be significantly worse in the massive type in the N1 group (p = 0.035).CONCLUSION:It seems necessary to take the morphological distribution of metastatic foci into consideration when dealing with node-positive patients who had received curative resection for gastric cancer.

We report a patient who developed severe biliary stenosis after undergoing cholecystectomy and hepatoduodenal ligament lymph node dissection for early gallbladder cancer. A 43-year-old man underwent cholecystectomy for gallbladder cancer, developed postoperative biliary stenosis, and again underwent surgery involving bile duct resection. The pathological diagnosis for the bile duct wall was a fibrous scar with no evidence of malignancy; therefore, the biliary stenosis was presumably secondary to disruption of the bile duct blood supply caused by lymph node dissection.