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The preservation of the axillary node (AN) has become standard therapy for early breast cancer patients with a metastasis-positive sentinel node (SN). However, about half of the patients with metastasis in the SN have no metastasis in the other AN. Late-phase three-dimensional computed tomographic lymphography (3D-CT LG) of the breast can show the axillary lymphatic architecture from the SN into the venous angle. These nodes are classified into five groups. For the sake of aesthetics, video-assisted breast surgery (VABS) was used to sample the second and third nodes shown by 3D-CT LG. For marking the SN on the skin, 3D-CT LG was performed the day before the surgery. Iopamiron 300 (2 ml) was injected subcutaneously. A 16-channel multidetector-row helical CT image was reconstructed to produce a 3D image of the lymph ducts and nodes. A biopsy of the SN was performed by the dye-staining method using Visiport-aided endoscopy for VABS. Stained nodes were located by following the dye in the lymph ducts on a video monitor. For SN-metastasis-positive patients, standard AN dissection was performed under video assistance. Since July 2002, the authors have performed SN biopsy for 186 patients as well as 3D-CT LG and VABS SN biopsy for 146 patients. Five chained-node groups were shown. Even in the multiple SN case, the lymph ducts were converging into the second node. The second and third nodes beyond the SN were detected and sampled in 82 patients (56.2%) by VABS assisted with 3D-CT LG. Sentinel node metastasis (n = 40) involved SN metastasis alone in 21 cases (52.5%) and SN, second-node, and third-node metastasis in eight cases. A reviewed lymphoid path by 3D-CT LG confirmed that metastasis occurred in order of lymph flow. The use of 3D-CT LG-guided VABS SN biopsy of the second and third nodes will predict SN metastasis alone and help to obviate the need for dissection of more nodes.

Aims: Recently, endoscopic mucosal resection (EMR) has become the first choice of treatment for superficial esophageal cancer without metastasis. However, EMR is not safe for all patients. Argon plasma coagulation (APC) is a noncontact electrocoagulation technique that creates tissue damage. The risk of bleeding may be lower with APC than with EMR. Therefore, we selected APC for the treatment of patients with superficial esophageal cancer who could not undergo EMR. The aim of the present study was to describe these cases and analyze the results of this treatment. Patients and Methods: Ten patients with superficial esophageal cancer underwent APC at our institution from February 2001 through January 2002. None of the patients could undergo EMR because of complications. Ablation was performed using an APC probe (ERBE APC probe; ERBE Elektromedizin, Tubingen, Germany), a high-frequency electrosurgical generator (ERBE ICC200), and an argon delivery unit (ERBE APC 300). All patients had uneventful recoveries. Results: No incidents of bleeding from the ablated lesion or infection occurred. Oral intake was resumed on the day after treatment. The mean duration of the procedure was 20 minutes (range, 10 to 40 minutes). Disease recurred in two patients. Two patients died of laryngeal cancer and liver failure, respectively. Conclusion: APC is a safe and easy to perform procedure, but the effect of therapy is inferior to that of EMR in terms of the complete resection of the lesion. In conclusion, APC should be limited to cases of superficial esophageal cancer without metastasis in which EMR has been deemed difficult.

Recent reports suggest that Helicobacter pylori infection can potentially increase the risk of colorectal cancer. The purpose of this study was to assess the association between H. pylori infection and the risk of colorectal adenoma and adenocarcinoma, and to evaluate any differences on the basis of sex. The subjects were 669 (40- to 80-year-old) patients who underwent both barium enema examination and total colonoscopy, and who were evaluated for H. pylori infection by 13C-urea breath test, urease test, or histological diagnosis of biopsied gastric specimens. There were 142 H. pylori-negative and 527-positive patients. The odds ratios (ORs) for H. pylori-positive patients with colorectal adenoma and adenocarcinoma, and for tumor patients with either adenoma or adenocarcinoma were calculated. Among the H. pylori-negative patients, there were 52 patients without tumor, 63 with adenoma, 27 with adenocarcinoma, and 90 with tumor. Among the H. pylori-positive patients, there were 136, 264, 127, and 391 patients respectively. Pooling all subjects, those infected with H. pylori had a significantly increased OR for adenoma, adenocarcinoma, or tumor, compared to H. pylori-free patients (OR, 1.60, 1.80, and 1.66, respectively). For female H. pylori-positive subjects, the risk of having adenocarcinoma or tumor was significantly higher than that for their H. pylori-free counterparts, while for male H. pylori-positive and -negative subjects, there was no such significant difference. The results therefore suggest that, in patients aged 40–80 years, H. pylori infection increased the risk of colorectal adenoma and adenocarcinoma, with significantly higher risks for female patients.

Gastrointestinal stromal tumor is a mesenchymal tumor of the digestive tract. Although there used to be no effective therapy for the tumor, there have been many recent reports on the efficacy of imatinib. We report on a 53-year-old female patient with a primary tumor of the jejunum who underwent 3 operations. As the tumor could not be removed at the 3rd operation, she was given imatinib orally. Results showed significant reduction ratios of the tumor area (83.0%) and volume (92.2%) at 18 months after starting imatinib administration. Also, the mean reduction ratios of the tumor area and volume per month (%/M) after starting imatinib treatment showed remarkable results, especially during the initial 3 weeks: 53.9%/M and 49.5%/M, respectively. Whether imatinib is the first choice of treatment for GIST or not, and what is the appropriate dose and period should be resolved.

A 63-year-old man presented to our hospital with persistent dysphagia. Radiologic and endoscopic examination disclosed a 2.0-cm exophytic tumor in the middle third of the esophagus. An endscopically obtained biopsy specimen was found to represent undifferentiated small cell carcinoma. Computed tomography of the chest, abdomen, and cervical region was performed, as were gallium and bone scintigraphy. Metastasis to an adjacent lymph node was detected, without metastasis to distant organs. After neoadjuvant chemotherapy with carboplatin (CBDCA) (400 mg/m2) and etoposide (VP-16) (100 mg/m2), endoscopy and barium-swallow esophagography showed regression. Thoracic esophagectomy then was performed with mediastinal, abdominal and cervical lymph node dissection. The resected tumor was polypoid, measuring 0.5 x 0.5 cm. The lesion consisted mainly of small anaplastic cells, but included a small focus of squamous cell carcinoma. The patient has survived for more than 7 months with no further treatment and no evidence of recurrent disease.

The Nippon Medical School New Tokyo International Airport Clinic(Airport Clinic)was opened in 1992 as Japan' s first 24‑hour international airport clinic. To date it has provided medical services to a total of 117953 patients. Of these 85545(72.5%)were airport employees 28662(24.3%)were passengers and 3746(3.2%)were others. Of the total non‑Japanese patients accounted for 8485(7.2%) . In the year to March 31 2001 the Clinic treated an average of 43.9 cases per day. The number of emergency patients was 2969 or 2.3% of the total of whom 500(0.4%) were non‑Japanese. There were 47 deaths with age ranging from 14 to 84(average age 64.0) . The ratio of males to females who died was 28: 19. Of the 47 deaths 18 were non‑Japanese. Pulmonary thromboembolism is considered to have played a role in 25 of the deaths. Based on more than 8 years of airport clinical experience we believe that a first‑class international airport should have excellent medical facilities that can provide quality emergency medical services to travelers and disaster victims. (J Nippon Med Sch 2002; 69: 185―191)

Background and Objectives Cyclin D1 is known to play important roles in the G1/S check-point of the cell cycle. We investigated the correlation between cyclin D1 overexpression and clinical characteristics to clarify its prognostic significance in patients with esophageal cancer. Methods From 1991 to 1998, cyclin D1 was investigated in esophageal cancers from 86 patients who underwent esophagectomy. Overexpression of cyclin D1 was demonstrated using an immunohistochemical method. Results Overexpression of cyclin D1 was found in 23 (26.7%) of 86 cases. Overexpression of cyclin D1 correlated with lymph node metastasis (P = 0.0083) and lymphatic vessel invasion (P = 0.018). Cyclin D1 overexpression may indicate resistance to chemotherapy. The patients with cyclin D1 overexpression had a significantly lower survival rate than those without overexpression (P = 0.013). The multivariate analysis revealed cyclin D1 overexpression to be an important prognostic factor in patients with esophageal cancer. Conclusions Immunohistochemical examination of cyclin D1 expression may provide important prognostic information in univariate and multivariate analysis and may be necessary for determining therapeutic strategies for esophageal cancer. J. Surg. Oncol. 2001;78:208–214. © 2001 Wiley-Liss, Inc.

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.

Evidence showed a marked decrease in recurrence rate of peptic ulcer after eradication of Helicobacter pylori infection. However, whether H. pylori infection is etiologically related to perforation of peptic ulcer remains to be clarified. We therefore conducted an age- and gender-matched case-control study between perforated and nonsurgical peptic ulcers in H. pylori infection and examined differences in the cytotoxin genes cagA and vacA. Serum H. pylori IgG antibody (ELISA) was positive in 20/21 (95%) of perforated vs. 37/40 (93%) of nonsurgical duodenal ulcers and in 5/5 (100%) of perforated vs. 24/28 (86%) of nonsurgical gastric ulcer patients. Positivity of H. pylori DNA in gastric juice, which was amplified by PCR and identified by Southern blot hybridization, was 17/23 (74%) of perforated vs. 32/45 (71%) in the nonsurgical duodenal ulcer group. Positivity of the cytotoxin genes cagA and vacA in H. pylori DNA-positive gastric juice was as follows : perforated vs. nonsurgical duodenal ulcer, cagA 11/ 13 (85%) vs. 24/27 (89%); vacA1: 9/13 (69%) vs. 22/27 (82%); vacA2 8/13 (62%) vs. 21/27 (78%). There were no significant differences between the perforated and nonsurgical peptic ulcer groups for these H. pylori serum and gene markers. It is assumed that H. pylori infection is not etiologically related to perforation of peptic ulcer.

BACKGROUND Gastric cancer is a multistage process, each caused by numerous factors. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiologic techniques and serum markers. METHODS Serum pepsinogen I levels, pepsinogen I/pepsinogen II (I/II) ratios, serum IgG antibody against Helicobacter pylori (H. pylori), and genetic polymorphisms of cytochrome p450 2E1 (CYP2E1), glutathione-S-transferase M1 (GSTM1), and L-myc protooncogenes were analyzed in 82 persons with gastric cancer and in 151 age- and sex-matched controls, who were selected from 208 gastric cancer patients and 375 noncancer patients, respectively. Statistical analysis was performed to elucidate which risk factors for gastric cancer were contributing the most to gastric carcinogenicity. RESULTS Serum pepsinogen I level (odds ratio [OR] = 1.81; 95% confidence interval [CI], 1.04–3.16) and pepsinogen I/II ratios (OR = 3.09; 95% CI, 1.74–5.49) were significantly associated with gastric cancer risk in a case–control study. Seropositivity of serum IgG antibody against H. pylori (OR = 1.25; 95% CI, 0.84–1.85) and specific genotypes of a L-myc genetic polymorphism (OR = 1.33; 95% CI, 0.59–2.99) were more commonly observed in gastric cancer cases, but this was not statistically significant. Specific genotypes of the CYP2E1 RsaI polymorphism and GSTM1 gene deletion were not associated with gastric cancer. CONCLUSIONS Atrophic mucosal change, indicated by serum pepsinogen levels, is possible a risk factor for gastric cancer. H. pylori infection and genetic polymorphisms of CYP2E1, L-myc, and GSTM1 genetic polymorphisms were not risk factors in this study. Cancer 1996;77:1654-61.

The detection of Helicobacter pylori in gastric juice by the polymerase chain reaction (PCR) was undertaken in 124 patients with peptic ulcer or chronic gastritis. PCR products were evaluated by agarose gel electrophoresis and Southern hybridization of H. pylori-specific DNA sequences. Positive and negative results of the PCR analysis in 72 examinations were compared with those from bacterial culture, and with the detection of tissue IgA antibody against H. pylori by enzyme-linked immunosorbent assay ELISA; Serion, Wuerzburg, Germany, and detection of serum IgG antibody against H. pylori by ELISA; Radim Pomezia, Italy. Thirty-four PCR-positive samples evaluated by electrophoresis and hybridization coincided with positive samples in 56% of bacterial cultures, 59% of tissue IgA antibody identifications, and 94% of serum IgG antibody evaluations; 26 PCR-negative samples coincided with negative samples in 96% of bacterial cultures, 81% of tissue IgA antibody evaluations, and 38% of serum IgG assessments. We compared the detection achieved with the H. pylori PCR assay in gastric juice with that in biopsies taken from the antrum and upper corpus in 90 examinations, and found them to be both positive in 34 (38%) and 36 (40%) of specimens, both negative in 37 (41%) and 30 (33%) specimens, gastric juice-positive but biopsy-negative in 10 (11%) and 12 (13%) specimens, and vice versa in 9 (10%) and 12 (13%) specimens, when detected by electrophoresis and hybridization, respectively, showing equivalent detection rates. In relation to the type of disease, the positive PCR assay results with gastric juice, evaluated by electrophoresis and hybridization, respectively, were: gastric ulcer 34/53 (64%) and 39/53 (74%), duodenal ulcer 23/38 (61%) and 25/38 (66%), and chronic gastritis 20/33 (61%) and 23/33 (70%), showing no significant difference in positive rates between peptic ulcer and chronic gastritis. Of the samples of 16 patients with H. pylori-positive gastric juice by the PCR assay, 7 were negative by PCR assay analyzed by electrophoresis and hybridization after the completion of treatment H. pylori. However, after treatment, 3 were negative on electrophoresis but still had positive results with hybridization, indicating that a minimal number of bacilli may have still remained. Detection of H. pylori in gastric juice has potential advantages for examining H. pylori infection in the entire stomach and for follow up after treatment for the eradication of H. pylori.

Chronic atrophic gastritis (CAG) is closely correlated with gastric cancer and is predominant in Japan. Epidemiologically, food habits are the primary factor in both CAG and gastric cancer. Two potential serum markers for CAG have recently been investigated, i.e., the concentration of serum pepsinogen (PG) and the presence of serum antibodies against Helicobacter pylori. Serum PG I and II and the PG I:PG II ratio have been reported to be useful as indicators of recurrent peptic ulcer and for screening of patients at risk from gastric cancer. In this study, we examined PG I and II in serum from 483 patients by RIA (DAINABOT), and endoscopic examination performed in the same patients before serological assay revealed CAG in 68, peptic ulcer in 91, and gastric cancer in 48. Analysis of the mean values according to patients age showed that CAG patients in their forties to eighties had low (40 ng/ml) levels of PG I, peptic ulcer patients in their teens to eighties had high (or = 70 ng/ml) levels, except for those in their seventies, and gastric cancer patients in their twenties to sixties had low (3.0) PG I:PG II ratios, except for those in their sixties. Thus serum PG assay has potential utility for detection of CAG, peptic ulcer, and gastric cancer.

A case of esophageal leiomyosarcoma, for which CT scan, endoscopic ultrasonography (EUS) and angiography were employed for preoperative diagnosis is reported. CT scan identified an exophytic mass which had no rim-enhancement in the lower end of the esophagus. EUS revealed a homogeneous mass originating from the muscularis propria. Angiography showed a mildly hypervascular tumor. Histologically, the resected specimen was a leiomyosarcoma. These results suggest that the evaluation by EUS combined with CT scan and angiography is useful in differentiating smooth muscle tumors from other submucosal tumors.

The hypothalamic-pituitary-adrenal axis is an essential component for the maintenance of homeostasis following trauma. Major surgical trauma often induces overwhelming inflammatory responses leading to sepsis and organ dysfunction. This study was designed to evaluate the adrenal responses both before and after various degrees of surgical trauma and to determine the incidence of postoperative relative adrenal insufficiency resulting in the marked inflammatory response often associated with postoperative complications. Fifty-one surgical patients were divided into groups who underwent major, moderate, and minor surgeries. Before the operation and during resting conditions, a short corticotropin (ACTH) stimulation test was performed in each patient. The postoperative concentrations of serum cortisol, interleukin (IL)-6, IL-10, C-reactive protein (CRP), and plasma ACTH were measured. Fifty of 51 patients were identified as responders to ACTH. The postoperative cortisol levels were the same as those obtained by ACTH stimulation in highly and moderately stressful surgeries. The increases in postoperative IL-6 and CRP levels were greatest with major surgery, intermediate with moderate surgery, and least with minor surgery. Furthermore, plasma ACTH levels increased after major and moderate surgeries; however, there was no significant differences in postoperative serum IL-10 levels. Systemic inflammatory response syndrome (SIRS) was found in 11 of 17 patients (64.7%) who underwent major surgery and in 4 of 16 patients (25%) who underwent moderate surgery (p=0.037). The duration of SIRS was significantly longer in patients undergoing major surgery (62+/-20 hrs) than in patients undergoing moderate surgery (21+/-3 hrs, p=0.038). Postoperative complications were more frequent in patients undergoing major surgery (41.2%) than in patients undergoing moderate surgery (6.3%, p=0.039). Furthermore, there were significant differences in the length of the postoperative stay among the three groups (p

We report 3 gastric cancer patients with peritoneal dissemination who were successfully treated with weekly paclitaxel and cisplatin. The patients were 2 men and 1 woman from 57 to 70 years in age. The histological types were 2 poorly-differentiated adenocarcinomas and 1 moderately-differentiated adenocarcinoma. Intravenous infusion of PTX (80 mg/m(2)) and CDDP (25 mg/m(2)) after short premedication was continued for 3 weeks followed by 1 week rest. Ascites improved only after administration of 1 course in all patients.PTX/CDDP is thought to be an effective chemotherapy showing acceptable toxicity against advanced gastric cancer with ascites.

Video-assisted breast surgery (VABS) is a less invasive and aesthetically better option for benign and malignant breast diseases and for sentinel lymph node biopsy (SLNB). The authors have performed 150 VABS procedures since December 2001. They have examined the usefulness of three-dimensional computed tomographic (3D-CT) lymphography for detecting sentinel lymph nodes (SLNs) precisely, as well as the cosmetic and treatment results of VABS. In this study, VABS was performed with a 2.5-cm skin incision in the axilla or periareola (1 cm in the axilla for SLNB), using a retraction method, for mammary gland resection, SLNB, axillary lymph node dissection, and breast reconstruction under video assistance. On the day before the surgery, 3D-CT lymphography was performed to mark SLN on the skin. Above the tumor and near the areola, 2 ml of Iopamiron 300 was injected subcutaneously. A 16-channnel multidetector-row helical CT scan image was taken after 1 min and reconstructed to produce a 3D image. Sentinel lymph node biopsy was performed by the VABS technique using the Visiport. The VABS procedure was performed for 19 benign and 131 malignant diseases, and 115 SLNBs (74 with 3D-CT) were performed. The SLNs were shown precisely by 3D-CT lymphography, as proved by a case of lymph node metastasis, in which accurate relationships between lymph ducts and SLNs were shown. These were classified into four patterns: a single duct to single node (40 cases), multiple ducts to a single node (13 cases), a single duct to multiple nodes (1 case), and multiple ducts to multiple nodes (12 cases). The SLNB procedure can be performed safely by 3D-CT lymphography and less invasively by VABS. The findings show that 3D-CT lymphography is useful for performing precise SLNB using VABS.

Lumican is a member of a small leucine-rich proteoglycan family, and it is reportedly overexpressed in human breast cancer. The expression of lumican in the extracellular matrix in breast cancer is associated with a high tumor grade, low estrogen receptor levels and young age. Lumican expression has been previously reported in colorectal cancer, but the role of lumican in the tumor is not well understood. In this study, we examined the expression and role of lumican in advanced colorectal cancer. Immunohistochemical staining was performed on 158 patients who underwent curative surgery for advanced colorectal cancer with lymph node metastasis. In the normal colorectal tissues, lumican immunoreactivity was observed in the fibroblasts and neural cells, but not in the colorectal epithelial cells. Lumican was localized in the cytoplasm of the cancer cells and its overexpression was detected in 99 of the 158 (62.7%) colorectal cancer patients. Clinicopathologically, there was no association of lumican expression with age, sex, histological typing, or venous and lymphatic invasion. However, lumican expression tended to correlate with the spread of lymph node metastasis and the depth of tumor invasion (p=0.136 and 0.135, respectively). Furthermore, the survival rate was significantly lower in patients with a high lumican expression level than in those with a low lumican expression level (p=0.048). These results indicate that lumican expression is a potential prognostic factor in patients with advanced colorectal cancer with nodal metastasis.

5-Fluorouracil (5-FU) and its derivatives are widely known as some of the most commonly prescribed anticancer drugs, especially for gastrointestinal cancer. Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. The activities of these enzymes may have the potential to affect the chemosensitivity of 5-FU.This study was designed to investigate the effect of OPRT, DPD and TS in sensitivity to 5-FU.We measured OPRT, DPD and TS activities in 11 colonic cancer tissues. The Collagen Gel Droplet Embedded Culture Drug Sensitivity Test (CD-DST) was used in an in vitro chemosensitivity assay. In these samples, the correlation between sensitivity to 5-FU and enzyme activities was investigated.There were no correlations among OPRT, TS activities and sensitivity to 5-FU. In contrast, there was a significant inverse correlation (r=-0.738) between DPD activity and 5-FU sensitivity. With regression analysis, the coefficient of determination of the activity of the three enzymes versus the sensitivity to 5-FU was 0.61.Though measuring OPRT, DPD, TS activities is valuable for prediction of sensitivity to 5-FU, DPD is considered to be the most important predictive factor of 5-FU sensitivity. To improve its accuracy, the finding of a fourth factor such as P-glycoprotein and multidrug resistance-associated proteins (MRP), to be added to OPRT, DPD and TS, is desired.

Orotate Phosphoribosyl Transferase (OPRT), Dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. In this study, we measured the activities of OPRT, DPD and TS. We also investigated the correlation between these 3 enzymatic activities and the clinical pathologic factors (Histological typing, extent of tumor invasion,extent of metastasis to the lymph nodes,stage, lymphatic invasion and venous invasion). We had surveyed 79 cases of colorectal cancers surgically removed. Poorly-differentiated adenocarcinoma showed a tendency to lower OPRT and higher DPD, as compared to moderately or well-differentiated adenocarcinomas. In case with metastasis to lymph nodes, OPRT showed a tendency to lower activities, but a significant difference was not noticed. TS showed no relation to any of these pathologic factors. In each application of 5-FU, measuring the activities of these three enzymes is important for estimation of the antitumoral effect. With poorly-differentiated adenocarcinoma, it is estimated that many cases would show high DPD and if the enzyme activities can not be measured, so administration of TS-1, which includes DPD inhibitor, may be considered.

Argon plasma coagulation (APC) is noncontact electrocoagulation technique that creates tissue damage. Recently, it has been reported that Barrett's esophagus and Barrett's adenocarcinoma in situ could be successfully managed by APC. The aims of this treatment are to prevent the developing of adenocarcinoma and to promote the restitution of normal squamous epithelium. Combined antireflux surgery or proton pump inhibitor therapy are indispensable to this treatment. Shorter length of Barrett's epithelium and normalization in pH with PPI treatment were the independent predictors of sustained long-term restitution of squamous epithelium. In patient with Barrett's esophagus, APC offers an effective, minimally invasive alternative to other treatments previously performed.

Hypoxia inducible factor (HIF)-1alpha is a transcription factor that regulates the transcription of genes associated with cell proliferation and vascular development. In various cancer tissues, HIF-1alpha is associated with clinicopathological factors, such as the tumor size, histological grade, and lymph node status. Although HIF-1alpha plays a critical role in tumor growth by inducing vascular endothelial growth factor (VEGF), it is unclarified whether HIF-1alpha affects lymphatic metastasis. The purpose of this study is to clarify the correlation of HIF-1alpha protein expression with lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The expressions of HIF-1alpha and VEGF-C, which is one of the main lymphangiogenic factors, were examined in five ESCC cell lines and 48 surgical specimens of ESCC. HIF-1alpha and VEGF-C mRNAs were expressed in all the five ESCC cell lines as determined by RT-PCR analysis. Immunohistochemically, 34 of the 48 patients (70.8%) were positive for HIF-1alpha and 29 patients (60.4%) were positive for VEGF-C. Clinicopathologically, HIF-1alpha expression correlated with lymphatic invasion and VEGF-C expression (P = 0.003 and P = 0.01, respectively). Furthermore, HIF-1alpha expression tended to correlate with lymph node metastasis (P = 0.09). These findings suggest that HIF-1alpha plays a role in lymphatic invasion and lymph node metastasis through the induction of VEGF-C in ESCC.

As no established histopathological criteria exist for assessing the malignant potential of gastrointestinal stromal tumor (GIST), recurrence or metastasis is occasionally observed in lesions diagnosed histopathologically as benign. The present study aimed to clarify the histopathological criteria for assessing the malignancy of GIST, from a clinical standpoint. The subjects were 22 patients with GIST expressing CD117 (c-kit) and/or CD34, who were followed up for more than 2 years. Clinically, GIST malignancy was diagnosed if any of the following criteria were met: peripheral invasive growth, lymph node metastasis, metastasis to another organ, peritoneal dissemination, recurrence, or death. GIST was also categorized as either benign or malignant by a new histological malignancy classification system, based on the determination of significant factors indicating malignancy in the clinical classification system above. Significant factors for malignancy identified in the clinical malignancy classification were: tumor hemorrhage/necrosis (present vs absent; P = 0.0053), tumor size (

Mucoepidermoid carcinoma of the esophagus (MEC) is uncommon and has not been fully investigated. The biological behavior and clinical aspects of MEC were studied. The clinical features of eight patients with MEC were compared with 51 cases of squamous cell carcinoma of the esophagus (SCC). Proliferating cell nuclear antigen (PCNA), p53, and carcinoembryonic antigen (CEA) were stained in the resected specimens by immunohistochemistry. Seven out of 8 cases (87.5%) had stage III by TNM classification. Four cases died of widespread metastases and 2 cases died of local recurrence within 2 years after the surgery. Neither chemotherapy and radiotherapy were effective against MEC. Overall median survival periods were 10.8 months for MEC and 32.1 months for SCC (P

The presence of lymph node metastasis is the most important prognostic factor in esophageal squamous cell carcinoma. Molecular biology techniques have improved the ability to recognize micrometastasis in lymph nodes, bone marrow, and peripheral blood. Previous studies have demonstrated that cytokeratin 19 reverse transcriptasepolymerase chain reaction can detect tumor cells even when lymph nodes appear normal histologically. However, the presence of pseudogenes for cytokeratin 19 have reduced the specificity of reverse transcriptase-polymerase chain reaction, thereby reducing its clinical worth as a sensitive diagnostic technique.We examined the expression of mRNA for cytokeratin 19 using a newly designed set of primers, and compared the results with data from histologic examinations. Samples were obtained from tumors, intact tissues, resected lymph nodes and in 10 patients who underwent esophagectomy via right thoracotomy with lymph node dissection in the neck, mediastinum and abdomen.All tumors, non-cancerous tissues were positive for cytokeratin 19 by reverse transcriptasepolymerase chain reaction. However, 2 of the 6 lymph nodes that appeared normal on histologic examination were positive for cytokeratin 19; sensitivity and specificity were 100% and 67%, respectively.Reverse transcriptase-polymerase chain reaction using new primers for cytokeratin 19 detected micrometastasis in specimens of lymph nodes from patients with squamous cell carcinoma. This method may increase the accuracy of tumor staging and provide clinicians with valuable information that will help individualize treatment options.

The effect of preoperative chemotherapy on prognosis is still controversial. We have investigated the relationship between responses to preoperative chemotherapy and prognosis after curative operations in patients with esophageal squamous cell carcinoma. Thirty-nine patients received preoperative chemotherapy with continuous infusion of 500 mg/m2 of 5-fluorouracil (5-FU) and intravenous injection of 20 mg/m2 of leucovorin every 12 hours for 5 days. On the 5th day alone, 70 mg/m2 of cisplatin was also infused. The effect was evaluated approximately 14 days after the end of one course of chemotherapy. The rates of responders and non-responders were 64.1% and 35.9%, respectively. After an interval of 21-28 days, transthoracic esophagectomy was performed. Significant histological effect by chemotherapy was found in responders compared to non-responders (P < 0.05). Responders had a significantly better prognosis than non-responders by Log-rank test (P < 0.01). This suggests that preoperative chemotherapy may contribute to better prognosis when the tumor is sensitive to chemotherapy.

Endoscopic mucosal resection (EMR) is currently a common treatment for superficial gastrointestinal tumors. We have developed new EMR scissors for superficial lesions in the esophagus and stomach. These scissors have stainless steel blades with an electrocoagulation device for hemostasis. We report a case in which superficial gastric cancer was treated by means of the EMR scissors. The lesion was removed using the scissors and no major complication was encountered. EMR scissors can be used for endoscopic resection of superficial lesions of the esophagus and stomach.

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.

An unusual case involving hemorrhage of a benign intrahepatic cyst in which the correct diagnosis was made preoperatively is reported. A 60-year-old man presented with acute onset of left upper quadrant abdominal pain. On admission, computed tomography and ultrasonography revealed an 8-cm hepatic cyst in the left lateral segment of the liver. Serum concentrations of CA19-9 (170 mu/mL), DUPAN2 (1600 mu/mL), and SPAN1 (94 mu/mL) were elevated. Twenty-three days after admission, magnetic resonance imaging revealed a hyperintense 13-cm lesion that appeared heterogeneous on T1-weighted sequences and relative hypointensity of the bottom on T2-weighted sequences. Percutaneous transhepatic drainage of the cyst was performed 27 days after admission, and serosanguineous fluid was obtained; abdominal pain resolved. Tumor marker concentrations decreased by 1 week after drainage. Six days after drainage, the drainage fluid became purulent. The infection persisted and a left lateral segmentectomy and cholecystectomy were performed 24 days after the cyst was drained. Pathology confirmed that the cyst was benign. The use of magnetic resonance imaging and tumor markers may allow the differentiation of benign hepatic cyst from malignant lesions and obviate the need for surgery.

Combined endoscopic injection sclerotherapy and endoscopic variceal ligation was used for the treatment of acute bleeding from gastric varices.Between July 1995 and August 1998, three cirrhotic patients with acute bleeding from gastric varices were treated. Endoscopic variceal ligation of the puncture point and bleeding point was performed simultaneously.Acute bleeding from the gastric varices was successfully stopped in all cases.Combined endoscopic injection sclerotherapy and endoscopic variceal ligation can be used to stop bleeding and prevent rebleeding from gastric varices.

Recent improvements in the treatment of gastric varices have resulted in better rates of hemostasis and eradication. This prospective study was conducted in order to examine the natural history of gastric varices and whether prophylactic treatment is required.Between January 1991 and December 1996, 52 patients with cirrhosis and no history of prior variceal treatment were enrolled.Bleeding from gastric varices occurred in 4 patients. Hemorrhage was stopped successfully in all of these patients. The cumulative bleeding rates at 1, 3, and 5 years were 3.8%, 9.4%, and 9.4%, respectively. Erosive gastritis or gastric ulcer was not detected in 3 of these 4 patients at the time of entry into the study, although an ulcer or erosion was found at the point of gastric variceal hemorrhage in all four patients at the time of variceal rupture. There were no significant differences in patient characteristics with ruptured versus non-ruptured varices at the time of their study entry.Factors which could be used to predict bleeding from gastric varices were not identified. Furthermore, the overall incidence of hemorrhage from gastric varices was found to be low. Once gastric variceal hemorrhage did occur, bleeding from these varices was successfully stopped in all cases. Therefore, prophylactic treatment of gastric varices is not recommended.

This study compared a new method, endoscopic scleroligation, intravariceal injection sclerotherapy followed by ligation plus extravariceal injection sclerotherapy, with ligation plus extravariceal injection sclerotherapy. Fifty-nine patients with cirrhosis and esophageal varices were treated by endoscopic scleroligation (ESL group, n = 28) or ligation plus extravariceal injection sclerotherapy (EVL + extraEIS group, n = 31). The demographics and clinical characteristics of the two treatment groups were similar, as was the rate of complete eradication with initial treatment. However, the 1- and 3-year cumulative recurrence rates in the ESL group (3.8% and 22.4%) were very significantly lower than those in the EVL + extraEIS group (48.3% and 81.0%) (p < 0.0001). The overall survival rates in the two groups were similar. In conclusion, endoscopic scleroligation is superior to ligation plus extravariceal injection sclerotherapy in preventing variceal recurrence. The efficacy of intravariceal injection sclerotherapy before ligation is believed to arise from the eradication of feeder vessels.

We describe herein a case of asymptomatic primary malignant melanoma of the esophagus. A 65-year-old man presented with a 4-cm filling defect in the middle third of the esophagus on a routine barium swallow. Subtotal esophagectomy accompanied by lymph node dissection was performed through a right thoracotomy. Postoperatively, the patient received five cycles of systemic chemotherapy with dacarbazine (DTIC), nimustine hydrochloride (ACNU), and vincristine (VCR) (DAV therapy), but ultimately died of generalized metastatic disease 15 months after surgery. Malignant melanoma of the esophagus has an extremely poor prognosis despite various therapeutic efforts.

Spontaneous gastrointestinal perforations in three patients with lymphoma were considered to be treatment-related conditions. All three were diagnosed as having malignant lymphoma by histological examination, and treated with chemotherapy and steroids. Four to 14 days after the start of chemotherapy, they complained of abdominal pain and plain roentgenograms revealed pneumoperitoneum. The interval between the onset of peritonitis and operation was almost 24 h. Emergency operations were carried out; one patient with a jejunal perforation underwent resection of the jejunum, another with a gastric perforation received a simple closure with omental patch, and the third with a gastric perforation underwent gastrectomy. Two patients recovered from the surgery, while the gastrectomy patient died due to sepsis. The favorable outcome of the surgical intervention is attributed to early diagnosis, prompt exploration, and selective operative procedures. We recommended a simple closure with omental patch for gastroduodenal perforation. Resection and primary anastomosis are possible only in the small bowel.

Anastomotic stricture is common after esophagogastrostomy. Recent advances in nonsurgical treatment include the silicon bougie and balloon dilatation. However, simple dilatation alone with a silicon bougie or endoscopic balloon dilator was repeated a mean of 4.7+/-5.4 times to control anastomotic stricture because of its temporary effect.For 11 patients, endoscopic injection of dexamethasone (8 mg) around the anastomosis was done immediately after balloon dilatation (40 psi for 5 minutes).This method significantly reduced the number of the dilatations to 1.1+/-0.3 (P0.05). Ten of the 11 patients did not need any further treatment. There were no side effects or complications of dexamethasone injection.A combination of endoscopic balloon dilatation and dexamethasone injection provided an easy and safe method for preventing the recurrence of anastomotic stricture.

Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA). Both host factors and H. pylori strain differences may contribute to differences in the diseases. Thus, we conducted an age and gender matched case-control study of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and gastric cancer (GCA) to examine the role of strain differences of the H. pylori cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain reaction to examine the gastric juice for H. pylori DNA. The test was positive for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients, showing no statistically significant difference among the diseases (P = 0.84). cagA and vacA genes (picked up by using a vacA1 + vacA2 primer pair which detected non-variable regions of the vacA gene) were detected by PCR in the H. pylori DNA-positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%; DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically significant differences were found in the frequencies of these cytotoxin genes in H. pylori-positive cases among the various gastric diseases (P = 0.39 for cagA and P = 0.64 for vacA).

To clarify the histology and morphogenesis of the double muscularis mucosae in Barrett's esophagus, eight specimens resected from patients with Barrett's esophagus were compared histopathologically with 352 specimens resected from patients without Barrett's esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barrett's esophagus, but in none of the 352 cases without Barrett's esophagus. The mucosa in the segment of Barrett's esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barrett's esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barrett's esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa.

We monitored the changes in serum neuron-specific enolase (NSE) level in two patients with esophageal small-cell carcinoma (SCC) during the course of treatment by chemotherapy or surgery, with radiation. Serum NSE levels at diagnosis were 18.5 and 58.0 ng/ml. In both cases, after treatment the serum NSE level decreased to within normal range (less than 10.0 ng/ml), concurrent with reduction in the size of the tumor. However, with relapse of the disease, the serum NSE increased to 24.3 and 200.0 ng/ml, respectively. One patient died of lung and skin metastases 4 months after surgery; the other, who developed brain metastasis, was treated again with chemotherapy by the same regimen. The serum NSE level decreased to 13.0 ng/ml, and the symptoms improved. These results indicate that there is a correlation between serum NSE level and remission or relapse of the disease after treatment in patients with SCC of the esophagus, as with SCC of the lung.

We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidin-biotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty-four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p less than 0.01), and also more often in cancers with lymph node metastasis than in those without (p less than 0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF-negative tumors (p less than 0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential.

Clinicopathologic data on 201 patients who underwent surgical resection of esophageal squamous cell carcinoma, with or without intramural metastasis (IM), were analyzed to determine the significance of IM for patient prognosis and survival. In 24 (11.9%) patients IM was observed. There was one (1.4%) in 74 cases in Stage 0, I, or 11, and 23 (18.1%) in 127 cases in Stage I11 or IV, based on the new pTNM classification. There was a statistically significant Cox-Mantel test difference in the percentage survival curves of the patients, both in all stages (P < 0.01) and in only Stages 111 and IV (P < 0.05), as a function of the presence or absence of 1M. Lymph node metastasis and distant organ metastasis were observed in 22 (91.7%) and seven (29.2%) of the 24 patients, respectively, with IM and in 111 (62.7%) and 13 (7.3%) of the 177 patients without IM. For both types of metastasis, the incidence was significantly lower in the patients without IM (P < 0.01). Seventy percent of IM on the proximal side was detected during preoperative clinical examination. These data indicate that the presence of IM is an important factor for preoperative and postoperative evaluation of the prognosis of patients with esophageal squamous cell carcinoma. Cancer 65:1816-1819,1990.