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Background Little is known about the survival outcomes of and predictive factors for survival in hemodialysis patients undergoing surgery for gastric cancer. Methods We performed a multicenter retrospective study from 9 institutions to investigate the survival outcomes of 75 hemodialysis patients with gastric cancer. Patient characteristics included demographic data, hemodialysis- and gastric cancer-related variables. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and non-gastric cancer related death. Results Stage I disease was predominant (58.7%) in our series. The overall morbidity and the 30-day mortality rates were 25.3% and 1.3%, respectively. The 5-year overall survival rates of patients with pStages I, II, III, and IV disease were 59.2%, 42.9%, 32.3%, and 0%, respectively. Eleven (14.7%) patients died of gastric cancer, whereas many more (40.0%) died owing to causes other than gastric cancer. Non-gastric cancer-related death was especially prevalent in patients with pStages I (95.2%) and II (75.0%) disease. Multivariable analysis revealed advanced age, long duration of hemodialysis (> 5 years), total gastrectomy, and pStage IV disease to be independently associated with poor overall survival. Notably, advanced age, long duration of hemodialysis, and the presence of cardiovascular disease were all independent predictors of non-gastric cancer-related death. Patients with all 3 factors had very poor survival outcomes (3-year overall survival; 14.3%). Conclusion The survival outcomes of hemodialysis patients with gastric cancer, especially those with early-stage gastric cancer, were clearly poor, largely owing to the increased risk of non-gastric cancer-related death. Preoperative comorbidities and hemodialytic features were useful for predicting long-term outcomes of this vulnerable population.

Gastroepiploic aneurysms are rare. We report the case of a 74-year-old man who presented with temporary loss of consciousness and abdominal pain. Computed tomography revealed a ruptured right gastroepiploic artery aneurysm. His vital signs improved after extracellular fluid infusion; hence, we performed transcatheter arterial embolization. There were no postoperative complications, and the patient was discharged on the 15th day of hospitalization. Ruptured abdominal aneurysms are often fatal and should be considered in patients with symptoms of anemia and abdominal pain. Currently, minimally invasive transcatheter arterial embolization had been designated as the preferred treatment option because of effectiveness in both diagnosis and treatment. Thus, we report a case of ruptured right gastroepiploic artery aneurysm treated by transcatheter arterial embolization, thereby preventing an emergency surgery.

A 79-year-old man presented with malaise and jaundice at a local hospital. His blood tests showed severe inflammation, liver failure, and high expression of several tumour markers. Radiological findings revealed dilated common and intrahepatic bile ducts and a lower bile duct constricted by a soft tissue mass. Histological findings by endoscopy showed a suspected adenocarcinoma, which was determined as class IV by cytology. The patient was referred to our hospital for surgical treatment. He underwent pancreaticoduodenectomy and the final diagnosis was so-called carcinosarcoma of the bile duct. He had liver metastasis and died at 26 postoperative months.

Background It is unclear how effective recombinant thrombomodulin (rTM) treatment is in disseminated intravascular coagulation (DIC) during the perioperative period of gastrointestinal and hepato-biliary-pancreatic surgery. The current study aimed to evaluate the therapeutic outcomes of rTM for perioperative DIC. Methods We enrolled 100 consecutive patients diagnosed with perioperative DIC after gastrointestinal surgery, and hepato-biliary-pancreatic including emergency procedures, between January 2012 and May 2021. Patients received routine rTM treatment immediately after DIC diagnosis. Then, the DIC, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated and used for evaluation. The outcomes of rTM treatment and the predictors of survival were evaluated. Results The causative diseases of DIC were as follows: perforated peritonitis, n = 38; intestinal ischemia, n = 23; intra-abdominal abscess, n = 13; anastomotic leakage, n = 7; pneumonia, n = 7; cholangitis, n = 4; and others, n = 6. The 30-day mortality rate was 18.0%. There were significant differences in the platelet count (13.78 vs 10.41, P = .032) and the SOFA score (5.22 vs 9.89, PConclusions Comprehensive and systemic treatment is fundamentally essential for DIC, in which rTM may play an important role in the treatment of perioperative DIC.

In radical surgery for upper cervical esophageal carcinoma, questions such as whether the larynx should be preserved depending on the distance from the esophageal orifice to the tumor margin and risk of aspiration during swallowing arise. We report the clinical outcomes of our strategy for upper cervical esophageal carcinoma based on the goals of curability and larynx preservation. Methods At our institution, resectable upper cervical esophageal carcinoma in which the tumor margin on the oral side is within 3 cm of the esophageal orifice is treated with chemoradiotherapy followed by larynx-preserving esophagectomy. The reason for initially using chemoradiotherapy is to make the surgical margin on the oral side completely negative and as distal as possible for definitive treatment and to improve quality of life (QOL). From 2016 to 2019, there were 24 patients who were diagnosed with upper cervical esophageal carcinoma within 3 cm of the esophageal orifice and received chemoradiotherapy and larynx-preserving esophagectomy. Results All patients were eligible for chemoradiotherapy and larynx-preserving esophagectomy. Pathologically, all surgical margins on the oral side were negative and all operations were curative. In particular, 6 patients with a tumor margin within 1 cm of the esophageal orifice underwent successful curative, larynx-preserving esophagectomy with the following additional techniques: incision of the cricopharyngeus muscle, lifting of the trachea and larynx, and rotation of the larynx to the left. Regarding surgical complications, 4 patients had temporary recurrent nerve paralysis with aspiration pneumonia and 1 patient had minor anastomotic leakage. Conclusion The combination of chemoradiotherapy and esophagectomy with a larynx-preserving technique is a useful treatment strategy for upper cervical esophageal carcinoma in terms of both definitive treatment and QOL.

A 44-year-old man presented to our hospital with lower gastrointestinal bleeding. We performed balloon-assisted enteroscopy, which revealed diverticulum and stricture at the ileum . The patient underwent segmental small bowel resection and diagnosed with Meckel's diverticulum. We should keep in mind the possibility of intestinal stricture due to Meckel's diverticulum.

Intrathoracic hernias after total gastrectomy are rare. We report the case of a 78-year-old man who underwent total gastrectomy with antecolic Roux-Y reconstruction for residual gastric cancer. He had alcoholic liver cirrhosis and received radical laparoscopic proximal gastrectomy for gastric cancer 3 years ago. Early gastric cancer in the remnant stomach was found by routine upper gastrointestinal endoscopy. We initially performed endoscopic submucosal dissection, but the vertical margin was positive in a pathological result. We performed total gastrectomy with antecolic Roux-Y reconstruction by laparotomy. For adhesion of the esophageal hiatus, the left chest was connected with the abdominal cavity. A pleural defect was not repaired. Two days after the operation, the patient was suspected of having intrathoracic hernia by chest X-rays. Computed tomography showed that the transverse colon and Roux limb were incarcerated in the left thoracic cavity. He was diagnosed with intrathoracic hernia, and emergency reduction and repair were performed. Operative findings showed that the Roux limb and transverse colon were incarcerated in the thoracic cavity. After reduction, the orifice of the hernia was closed by suturing the crus of the diaphragm with the ligament of the jejunum and omentum. After the second operation, he experienced anastomotic leakage and left pyothorax. Anastomotic leakage was improved with conservative therapy and he was discharged 76 days after the second operation.

Cases of skeletal muscle metastasis of esophageal carcinoma are very rare, with few reports of long-term survival. We report a case of long-term survival after surgical resection of skeletal muscle metastasis. A 56-year-old man with advanced esophageal cancer and early gastric cancer underwent thoracoscopic esophagectomy, 2-field lymph node dissection, partial gastrectomy and gastric tube reconstruction. Six months later, cervical lymph node metastasis and mediastinal lymph node recurrence were found. Therefore, the patient underwent cervical lymph node dissection and adjuvant chemoradiotherapy. Two years and 3 months after the esophagectomy, a muscle metastasis was found in the left shoulder, and he underwent tumor dissection, followed by adjuvant chemotherapy for a year. There has been no sign of recurrence since, even 13 years after the esophagectomy. We believe our aggressive surgical treatment might have led to long-term survival.

In this study, we determined the possible usefulness of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the management of gastric cancer.ICG fluorescence imaging system has recently been developed for obtaining biochemical information from living tissues.Our series consisted of 56 patients with gastric cancer who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG solution (0.5%) was injected into the submucosa around the tumor endoscopically before the operation or into the subserosa intraoperatively. ICG fluorescence imaging was conducted using a charge-coupled device camera with a light-emitting diode having a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector.SNs were detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/- 7.0. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. cT1-stage cancers were associated with a significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3-stage cancers. Preoperative ICG injection was associated with a significantly higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P0.0001), a higher accuracy rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%, P = 0.0345) as compared with intraoperative ICG injection.This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

大腸癌におけるリンパ節転移個数の予後規定因子としての有用性を検討した.1981年から2000年までに経験した大腸癌症例のデータベースよりstage IIIa,IIIbを抽出した.生存率の比較はKaplan-Meier法とLog-rank testを用い,多変量解析はCox regression modelを適用した.stage IIIa126例,stage IIIb78例,計204例が解析の対象となった.リンパ節転移個数は,深達度がse(a2)以深で有意に多数であり(P=0.0003),大腸癌取扱い規約におけるリンパ節転移分類(n因子)がn1,n2,n3になるに従って有意に多くなった(P

Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 ( P =0.033), 7q21.3 ( P P =0.013), 7q36 ( P =0.033), and 22q11.2 ( P =0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.

科学的根拠に基づく結腸癌手術のクリニカルパス(CP)を作成した.CPの適応の要点は米国麻酔学会(ASA)分類1度と2度の定期手術症例である.CPの骨子は(1)術前後のインフォームド・コンセント,(2)術後胃管非留置,(3)硬膜外鎮痛法,(4)早期離床,(5)早期経口摂取,(6)第6病日退院,である,CP導入前の非CP群とCP導入後のCP群の各々42例を対象にし,臨床成績を比較検討した.年齢,性,併存疾患の比率,手術時間,出血量,術式の比率は各々両群問に有意の差はなかった.CP群は非CP群よりDukes Bが有意に少なかった.術後合併症の頻度は両群間に有意の差は認められなかった.術後入院期間の中央値は非CP群20日(8～100),CP群は6日(3～31)であり,CP群は有意に短期間(P

教室の過去のLおよびM領域の単発SM胃癌切除例(n=258)のリンパ節転移,再発形式より, SM胃癌の至適リンパ節郭清について検討した.リンパ節転移はpN0 79.8%, pN1 16.3%, pN2 3.1%, pN3 0.8%であった. pN2症例にNo.11p, 12a, 14v転移は認めなかった.多変量解析で有意差を認めた予後因子はリンパ節転移と静脈侵襲の有無であり,リンパ節郭清程度は有意ではなかった.再発形式は血行性再発が60%と最多であり, pN0, pN1例の再発死亡は各3例でリンパ節再発は認めなかった.また, sN0例に再発は認めず, sN1例にリンパ節再発は認めなかった.以上より, sT1 (SM), sN1例に対する,ガイドラインで推奨されている現規約D2郭清による予後改善の可能性は低いことが示唆された.

Loop colostomy prolapse is associated with an impaired quality of life. Surgical treatment may sometimes be required for cases that cannot be closed by colon colostomy because of high-risk morbidities or advanced disease. We applied the Altimeter operation for patients with transverse loop colostomy. The Altemeier operation is therefore indicated for rectal prolapse. This technique involves a simple operation, which includes a circumferential incision through the full thickness of the outer and inner cylinder of the prolapsed limb, without incising the abdominal wall, and anastomosis with sutures using absorbable thread. We performed the Altemeier operation for three cases of loop stomal prolapse. Those patients demonstrated no postoperative complications (including obstruction, prolapse recurrence, or hernia). Our findings suggest that this procedure is useful as an optional surgical treatment for cases of transverse loop colostomy prolapse as a permanent measure in patients with high-risk morbidities or advanced disease.

完全直腸脱に対してDelorme手術を行い,術後6カ月以上経過した12例を対象に術前後の排便機能を評価した.平均年齢は75歳,男女比は3:9であった.術後観察期間の中央値は2年2カ月であり,この間に再発を1例認めた.便失禁は7例中4例で改善し,術後排便困難をきたした例はなかった.便意と便とガスの識別の回復は各々60%,33%でみられた.肛門内圧検査では肛門管最大静止圧と最大随意収縮圧は術後有意に高値となった.直腸感覚検査では便意発現最小量と最大耐容量は術後有意に低値になった.このような括約能と直腸感覚の改善により便失禁の改善が得られ,排便困難症の防止になったと推察された.

Background. Superficial duodenal neoplasms (SDNs) are a challenging target in the digestive tract. Surgical resection is invasive, and it is difficult to determine the site and extent of the lesion from outside the intestine and resect it locally. Endoscopic submucosal dissection (ESD) has scarcely been utilized in the treatment of duodenal tumors because of technical difficulties and possible delayed perforation due to the action of digestive juices. Thus, no standard treatments for SDNs have been established. To challenge this issue, we elaborated endoscopy-assisted laparoscopic full-thickness resection (EALFTR) and analyzed its feasibility and safety.Methods. Twenty-four SDNs in 22 consecutive patients treated by EALFTR between January 2011 and July 2012 were analyzed retrospectively.Results. All lesions were removed en bloc. The lateral and vertical margins of the specimens were negative for tumor cells in all cases. The mean sizes of the resected specimens and lesions were 28.9 mm (SD ± 10.5) and 13.3 mm (SD ± 11.6), respectively. The mean operation time and intraoperative estimated blood loss were 133 min (SD ± 45.2) and 16 ml (SD ± 21.1), respectively. Anastomotic leakage occurred in three patients (13.6%) postoperatively, but all were minor leakage and recovered conservatively. Anastomotic stenosis or bleeding did not occur.Conclusions. EALFTR can be a safe and minimally invasive treatment option for SDNs. However, the number of cases in this study was small, and further accumulations of cases and investigation are necessary.

Accurate prediction of the metastatic status of lymph nodes (LNs) is clinically important for selecting treatment strategies in patients with gastric cancer with submucosal invasion (GCSM). In this study, we determined the risk factors for lymph node metastasis (LNM), including micrometastasis, in patients with GCSM. A total of 5610 LNs dissected from 189 patients with GCSM who had undergone a standard gastrectomy were immunostained with CAM 5.2 monoclonal antibody to detect LN micrometastasis. Clinicopathological risk factors for lymph node metastasis (LNM), including micrometastasis, were determined. LNM was detected in 216 LNs (107 macroscopic metastases, 72 micrometastases, and 37 isolated tumor cells) in 55 (29.1%) of the 189 patients with GCSM. A multivariate analysis revealed that a tumor size of more than 20 mm, a mixed- or undifferentiated-type histology, a vertical tumor invasion depth in the submucosal layer (VTIDSM) of more than 0.5 mm, and the presence of lymphatic vessel invasion (LVI) were independent risk factors for LNM. The incidences of LNM in patients with 0, 1, 2, 3, and 4 risk factors were 0, 4.5, 11.4, 36.1, and 52.9%, respectively. Among the patients with only 1 or 2 risk factors, all the metastatic lesions were located only in the first tier. On the other hand, LNM in the second tier was also detected in 24.5% of the patients with more than 3 risk factors. Tumor size, histologic type, VTIDSM, and LVI are important risk factors for predicting the presence and extent of LNM in patients with GCSM.

Indocyanine green (ICG) fluorescence imaging has recently been reported as a new method for sentinel node (SN) mapping in several types of cancers. In this study, we determined the possible usefulness of SN mapping guided by ICG fluorescence imaging during laparoscopy-assisted gastrectomy (LAG) for gastric cancer. Our series consisted of 77 patients with cT1- or cT2-stage gastric cancer who had undergone LAG (LAG group; 38 patients) or conventional open gastrectomy (OG group; 39 patients). Intraoperative SN mapping guided by ICG fluorescence imaging was conducted with a charge-coupled device camera with a light-emitting diode as the light source and a cut filter as the detector. The detection rate and mean number of fluorescent nodes (FNs) were 94.7% and 7.9, respectively, in the LAG group, and 94.9% and 7.2, respectively, in the OG group. The accuracy and false-negative rates were 97.2% (35 of 36 cases) and 25% (1 of 4), respectively, in the LAG group, and 91.9% (34 of 37) and 23.1% (3 of 13), respectively, in the OG group. Among 33 LAG group patients and 27 OG group patients without FN metastasis, lymph node metastasis was found only in non-SNs located in the same lymphatic basin as the detected FNs. SN mapping guidance by ICG fluorescence imaging could be useful for predicting the lymph node metastasis in gastric cancer, even during LAG. Our data suggest that dissection of the lymphatic basin containing FNs with laparoscopic surgery may be a promising approach as a new type of minimally invasive surgery for patients with cT1- or cT2-stage gastric cancer having no metastasis in FNs.

Background: Recently, gastrointestinal cancer has also been identified as a target for sentinel node navigation surgery (SNNS). This study is the first to determine the feasibility of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in gastrointestinal cancer. Methods: Our series consisted of 22 patients with gastric cancer and 26 patients with colorectal cancer who had undergone standard surgical resection. ICG solution was injected intraoperatively into the subserosa around the tumor. Fluorescence imaging was obtained by a charge-coupled device (CCD) camera with a light-emitting diode with a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. Results: Immediately after the ICG injection, lymphatic vessels draining the tumor and round-shaped SNs were visualized by their bright fluorescence. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. The SN detection rate and mean number of SNs were 90.9% and 3.6 ± 4.5 (mean ± SD), respectively, in patients with gastric cancer, and 88.5% and 2.6 ± 2.4, respectively, in patients with colorectal cancer. Among the patients with gastric cancer, the accuracy and false-negative rates were 88.9 and 33.3%, respectively, in patients with T1 stage cancer, and 70.0 and 60.0%, respectively, overall, in all the patients. Among the patients with colorectal cancer, the corresponding values were 100 and 0%, respectively, in patients with T1 stage cancer, and 82.6 and 66.7%, respectively, overall, in all the patients. Conclusions: Our preliminary results show that ICG fluorescence imaging allows easy, highly sensitive and real-time imaging-guided SN mapping in patients with gastric or colorectal cancer. SN mapping guided by ICG fluorescence imaging could be a promising tool deserving further clinical exploration.

Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P=0.0006 and 72.2 vs 55.3%, P=0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P=0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P=0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P=0.0402 and 51.5 vs 84.6%, P=0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P=0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.

Purpose: Gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. In the present study, we determined the clinicopathologic significance of phenotypic marker expression in early-stage gastric differentiated-type tumors and the association between marker expression and genetic alterations. Experimental Design: Phenotypic marker expression was determined by examining the expressions of human gastric mucin (HGM), MUC6, MUC2, and CD10 in 63 gastric adenomas, 133 early differentiated-type carcinomas, and 24 follow-up cases with gastric adenoma. Tumors were classified into gastric, gastric and intestinal mixed, or intestinal phenotypes according to the immunopositivity of the above markers. The presence of mutations in APC, K-ras, and p53 and the microsatellite instability status were also determined in all tumors. Results: The expressions of HGM and MUC6, representing gastric or gastric and intestinal mixed phenotypes, were significantly associated with high-grade atypia in the 63 gastric adenomas. Among the 133 early differentiated-type carcinomas, HGM expression was significantly associated with mixed-type (with an undifferentiated-type component) tumors and lymph node metastasis. MUC2 expression was inversely associated with submucosal invasion. A multivariate analysis revealed that gastric adenomas were significantly associated with the intestinal phenotype and were inversely associated with p53 mutation compared with early differentiated-type carcinomas. Among all 196 tumors, APC mutation was significantly associated with CD10 expression and the intestinal phenotype and was inversely associated with the expressions of HGM and MUC6. The microsatellite instability status was significantly associated with MUC6 expression. Malignant transformation from gastric adenoma to carcinoma was shown in 5 of the 24 follow-up cases of gastric adenoma. The malignant transformation was significantly associated with the gastric and intestinal mixed phenotype and was inversely associated with APC mutation. No malignant transformation was found in intestinal phenotype gastric adenomas with APC mutation. Conclusions: Our present findings show that phenotypic marker expression is associated with tumor aggressiveness during the early stage of gastric differentiated-type tumors. Differences in the biological behavior of tumors with different phenotypes may result from differences in the genetic backgrounds during the incipient phase of gastric tumorigenesis.

Gastric and intestinal phenotypic cell markers are widely expressed in gastric carcinomas, irrespective of their histological type. In the present study, the relations between the phenotypic marker expression of the tumour, histological findings, expression of cell adhesion molecules, and the chromosomal changes in gastric differentiated-type carcinomas were examined. The phenotypic marker expression of the tumour was determined by the combination of the expression of the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in comparison with the expression of cell adhesion molecules, such as E-cadherin and beta-catenin, and chromosomal changes by comparative genomic hybridization (CGH) in 34 gastric differentiated-type carcinomas. Tumours were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of staining for HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with a higher incidence of differentiated-type tumours mixed with undifferentiated-type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%, P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%, P=0.0135). GI-phenotype tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with I-phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were significantly associated with higher frequencies of the gains of 19q13.2 and 19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs 13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly associated with higher frequencies of the gains of 20q13.2, compared with MUC6-negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%, P=0.0481). Our present results show that gastric differentiated-type carcinomas have different characteristics according to the phenotypic marker expression of the tumour in terms of histological findings, E-cadherin expression and pattern of chromosomal changes.

Both gastric and intestinal phenotypic markers are known to be expressed in gastric carcinomas, irrespective of their histologic type. In the present study, the relation between gastric and intestinal phenotypic marker expression in gastric carcinomas and the recurrence pattern after surgery was examined. The phenotypic marker expression of the tumour was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10 in 213 advanced gastric carcinomas in 213 patients who had undergone a curative resection (97 died from recurrent gastric carcinoma and 116 were alive without recurrence at the end of the follow-up period). Tumours were classified into gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotypes according to the immunopositivity of HGM, MUC6, MUC2 and CD10 stainings. The incidence of HGM-positive tumours and MUC2-negative tumours was significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (73.3%, 44 out of 60 cases vs 54.3%, 63 out of 116 (P=0.022); and 70.0%, 42 out of 60 vs 38.8%, 45 out of 116 (P=0.0002), respectively). The incidence of G-phenotype tumours was also significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (58.3%, 35 out of 60 cases vs 28.4%, 33 out of 116 (P=0.0002)). The incidence of MUC2-negative tumours and CD10-positive tumours was significantly higher in tumours with haematogenous recurrence than in tumours without recurrence (62.5%, 20 out of 32 cases vs 38.8%, 45 out of 116 (P=0.028); and 43.8%, 14 out of 32 vs 23.3%, 27 out of 116 (P=0.039); respectively). Our present findings show that the gastric and intestinal phenotypic marker expression of the tumour, determined by immunohistochemical staining for HGM, MUC6, MUC2 and CD10, can be used to predict the pattern of gastric carcinoma recurrence after curative resection.

The preventive effect of oral administration of viable Lactobacillus casei strain Shirota (LcS) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and colon cancers in the rat was investigated. The study consisted of two experiments; in a short-term experiment (Exp-I), the inhibitory effect of 8- and 12-week treatments with LcS. Forty rats each received weekly a subcutaneous injection of AOM at a dose of 15 mg/kg of body weight for 5 weeks. Eight and twelve weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon and the mesenteric lymph nodes (MLN) were removed. The number of ACFs and the surface marker of lymphocytes derived from the MLN were investigated. The large ACF (those comprising four or more aberrant crypts per focus) had significantly decreased in the rats which had consumed the LcS diet. And oral administration of viable LcS significantly recovered CD8 positive lymphocytes to the levels in the control group. In a long-term experiment (Exp-II), 30 rats each received weekly a subcutaneous injection of AOM at a dose of 7. 4 mg/kg of body weight for 10 weeks. Twenty-five weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon were removed. The number and incidence of colon cancers were investigated. The number of rats with colon cancers and the number of colon cancers per rat, were significantly decreased in the rats which had consumed the LcS diet. LcS inhibited chemically-induced colon carcinogenesis in the rat. CD8 positive T lymphocytes may play a key role in the preventive effect against colon carcinogenesis.

AIM: To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors. METHODS: We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors. RESULTS: Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively). CONCLUSION: The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.