倉科 憲太郎

The patient is a 61-year-old man who had previously undergone an extended thymectomy for myasthenia gravis. Endoscopic examination during a routine follow-up visit revealed early gastric cancer in the proximal portion of the stomach. To undergo resection the patient received general and epidural anesthesia. The conditions were unfavorable for laparoscopic-assisted surgery because he had a body mass index of 33 and muscle relaxants could not be used. Pneumoperitoneum was induced with carbon dioxide, and the abdominal wall was lifted. An adequate working space was secured in the upper abdomen and proximal gastrectomy was successfully performed.

We report a case of a 51-year-old man with esophageal cancer who had a complete pathological response to preoperative chemotherapy with a combination of docetaxel, cisplatin and 5-fluorouracil (DCF). Endoscopy and esophagography showed a type II tumor 8 cm in diameter, located in the upper thoracic esophagus. On computed tomography the diagnosis was T3N1M0, stage III disease according to TNM classification. Before surgery, the patient received DCF therapy, consisting of docetaxel (60 mg/m(2)) on day 1, cisplatin (60 mg/m(2)) on day 1, and 5-fluorouracil (800 mg/m(2)) on days 1-5. The patient had grade 3 hematological toxicity, but two courses were administered as scheduled. After chemotherapy, esophagography and computed tomography showed that the tumor had shrunk. Esophagectomy with three-field lymph node dissection was performed. Histopathologically, an ulcer scar was found, with no residual cancer cells. There were no metastases in dissected lymph nodes. This regimen is considered to have a high potential.

BACKGROUND: Quality of life is an important outcome measure in the care of patients with cancer. We developed a new scoring system specifically for the evaluation of patients with upper gastrointestinal cancer and postoperative gastrointestinal dysfunction. This study was undertaken to evaluate the scoring system's validity in comparing outcomes after gastric resection. MATERIALS AND METHODS: Patients with gastric cancer, 3 months to 3 years postoperatively, were surveyed using the survey instrument. Postoperative dysfunction scores and the status of resuming activities of daily living were compared with the surgical procedure performed by analysis of variance and multiple-comparison techniques. RESULTS: Of 211 patients surveyed, 165 (119 men, 46 women; mean age, 65.1 ± 10.5 years) responded. Procedures included distal gastrectomy in 100, total gastrectomy in 57, and pylorus-preserving gastrectomy in 8. The overall dysfunction score was 61.8 ± 15.5. The dysfunction score was 58.9 ± 15.0 after distal gastrectomy, 66.8 ± 14.1 after total gastrectomy, and 62.4 ± 21.6 after pylorus-preserving gastrectomy. These values differed significantly among the groups (P = .007). Dysfunction scores according to postoperative activity status were 49.1 ± 15.6 in 71 patients who resumed their activities, 56.9 ± 15.7 in 39 patients with reduced activities, 57.3 ± 8.8 in 15 patients with minimal activities, and 63.3 ± 11.8 (P < .05) in 16 patients who did not resume activities because of poor physical condition. CONCLUSIONS: This scoring system for postoperative gastrointestinal dysfunction provides an objective measure of dysfunction related to specific surgical procedures and correlates with activities of daily living in the postoperative period.

BACKGROUND: In patients with adverse events of S-1, the dose is generally reduced or the treatment cycle is shortened. Whether the therapeutic effectiveness of modified regimens is similar to that of the standard dosage remains unclear. METHODS: We retrospectively studied patients with gastric cancer who received S-1 on alternate days. RESULTS: A total of 266 patients received S-1 on alternate days. In 116 patients, S-1 was initially given at the standard dosage but was switched to alternate-day treatment because of toxicity within 28 days on average. The other 150 patients initially received alternate-day treatment because of poor general condition. In the adjuvant chemotherapy group (n = 96), the 3-year survival rate was 88% in patients with stage II, 73% in stage IIIA, and 67% in stage IIIB who underwent D2 lymph-node dissection. In the palliative surgery group (n = 96), the response rate was 13%, with a median survival time (MST) of 624 days. In patients with unresectable/recurrent disease (n = 74), the response rate was 25%, with an MST of 338 days. Among the 116 patients who initially received treatment on consecutive days, 100% had grade 1, 53% had grade 2, and 5.2% had grade 3 adverse events. When S-1 was switched to alternate-day treatment, toxicity decreased in all patients. In the 266 patients who received alternate-day treatment, 8% had grade 1, 6% had grade 2, and 0% had grade 3 adverse events. CONCLUSION: Alternate-day treatment with S-1 may have milder adverse events without compromising therapeutic effectiveness.

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract.

To identify novel cancer-promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non-cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ.

The purpose of this study was to screen for genes involved in ovarian carcinogenesis in an attempt to develop an effective molecular-targeted therapy for ovarian cancer. We constructed retroviral expression libraries for the human ovarian cancer cell lines SHIN-3 and TYK-CPr, and performed a focus formation assay with 3T3 cells. As a result, proteasome subunit beta-type 2 (PSMB2), ubiquitin-specific protease 14 (USP14), and keratin 8 (KRT8) were identified from SHIN-3, and polymerase II RNA subunit (POLR2E), chaperonin containing T-complex polypeptide 1 subunit 4 (CCT4), glia maturation factor beta (GMFB), and neuroblastoma ras viral oncogene homolog (NRAS) from TYK-CPr. NRAS gene analysis revealed a CAA --> AAA substitution at codon 61, resulting in a Glu --> Lys change at position 61. When the mutant NRAS was introduced into fibroblasts for its expression, many transformed foci were generated, confirming the transforming ability of the mutant NRAS.

Background/Aims: Laparoscopic-assisted distal gastrectomy (LADG) is a minimally invasive procedure for patients with gastric carcinoma. We have previously reported gasless LADG with a Billroth-I reconstruction using a 5-7cm mini-laparotomy. We modified the technique for gasless LADG to include a Roux-en Y reconstruction and to expand the indications for its use. Methodology: A total of 40 patients with early stage gastric tumors (T1 n=38, T2 n=2) underwent this procedure. Following gasless laparoscopic distal gastrectomy with lymph node dissection, a jejunum to greater curvature of the gastric remnant anastomosis was performed using an intracorporeal laparoscopic stapled method. The jejuno-jejunal anastomosis was performed using a hand-sewn technique under direct vision through a mini-laparotomy. Results: The mean surgical time (n=40) was 222min, estimated blood loss 101ml, and the mean number of lymph nodes harvested was 21. There were no postoperative complications such as bleeding, leak, or cardio-pulmonary dysfunction. Mean body weight loss was 3.9 kg, and there is no evidence of recurrence during a mean follow-up of 14 months. Conclusions: Gasless LADG with Roux-en-Y reconstruction is a feasible, novel procedure for a minimally invasive approach to gastric cancer.

Esophageal carcinosarcoma is an extremely rare tumor, and surgery is the mainstay of treatment. We report two patients with carcinosarcoma of the esophagus who received neoadjuvant chemoradiotherapy and underwent curative resection. Patient 1 was a 50-year-old man with a type 2 lesion in the upper thoracic esophagus; clinical stage was T3 or partial T4N1M0. After chemoradiotherapy the tumor and the lymph nodes become smaller, and subtotal esophagectomy was performed. Patient 2 was a 66-year-old man with a protruding lesion in the lower thoracic esophagus. Preoperative chemoradiotherapy was administered, and he had a partial response. However, surgery was postponed because of pneumonia; 11 months later, tumor enlargement was confirmed and we then performed subtotal esophagectomy. The therapeutic role and effectiveness of both chemotherapy and radiotherapy remain unclear. We reviewed 26 previously reported cases of esophageal carcinosarcoma treated by chemotherapy, radiotherapy, or both. These findings suggest that preoperative chemoradiotherapy may be effective for downstaging the primary tumor in patients with advanced esophageal carcinosarcoma.

A 67-year-old woman underwent resection of a gastric tumor and a synchronous metastatic lesion of the liver in 1991. Histopathologically, both the primary and metastatic tumors were diagnosed as leiomyosarcoma. Four years after the initial resection, another liver metastasis was detected in the caudate lobe, and a partial hepatectomy was performed. Multiple bilateral lung metastases were identified 7 years later and one was resected. Immunohistochemically, tissues from both the primary and metastatic sites were positive for KIT and CD34, and a c-kit gene mutation was found in the resected lung lesion. The remaining lung metastases responded to treatment with imatinib mesylate, but the treatment was discontinued because of toxicity. The patient remains under observation and the lung lesions have not progressed. At present she has no symptoms, and she has had no further recurrences in the past 3 years. This case is extremely unusual; a slowly progressing gastrointestinal stromal tumor over the course of 17 years from the initial diagnosis, with hematogenous metastases at multiple sites.

BACKGROUND: Pancreatic carcinoma causes more than 20,000 deaths every year in Japan. The role of (neo-) adjuvant chemotherapy for pancreatic carcinoma is still controversial. METHODS: At the 34th Annual Meeting of the Japanese Society of Pancreatic Surgery in 2007, questionnaires were distributed regarding the use of (neo-) adjuvant chemo(radio)therapy for pancreatic carcinoma between 2001 and 2005. RESULTS: Sixty of the 146 member institutions responded to the questionnaires. There were a total of 1,846 cases of resected pancreatic carcinoma between 2001 and 2005. The study population had a greater proportion of males, and a mean age of 65.3 years (range 34-90 years). The lesion was located in the head of the pancreas in 1,204 cases (71.7%), in the body in 353 cases (21.0%), and in the tail in 111 cases (6.6%). Overall survival rates were 67.3% at 1 year, 36.0% at 2 years, and 23.9% at 3 years, respectively. Adjuvant chemotherapy (usually involving gemcitabine) was used in 66.0% of cases. The use of adjuvant chemotherapy was found to improve the overall survival rate. Interestingly, adjuvant chemotherapy only improved survival in late-stage (UICC stages IIB, III, and IV) but not early stage (IA, IB, and IIA) patients. Survival was treatment duration-dependent, with patients who received more than 12 months of therapy having a 3-year survival rate of 51.2%. CONCLUSION: This high volume retrospective data indicated the promising effect of gemcitabine-based adjuvant chemotherapy and the rational duration of adjuvant chemotherapy should be determined in the future prospective studies.

BACKGROUND: The toxic effects of S-1 can lead to discontinuation of treatment. Strategies for reducing toxicity without compromising therapeutic effectiveness are required. METHODS: We used the human gastric cancer cell lines MKN28 and MKN45 to examine such strategies in vitro. The cell lines were treated with three different regimens, given on alternate days (alternate-day) or on consecutive days (consecutive-day). On consecutive days, treatment A provided the same total dose as the alternate-day treatment, and treatment B was given for the same number of days as the alternate-day treatment. A fourth group served as control. In vitro, the relative inhibition (RI) of tumor growth by 5-fluorouracil was calculated using the 2-(2-methyl-4-nitrophenyl)-3-(4-nitrophyl)-5-2, 4-disulfophenyl)-2H-tetrazolium (WST-8) method. We also carried out an in vivo experiment in which tumor-bearing nude mice (BALBc/nu-nu) were used to examine the antitumor activity of S-1. Leukocyte counts and gastrointestinal mucosal injury were compared in mice that received alternate-day and consecutive-day treatments. RESULTS: In vitro, for MKN28, the RI was 22.9% for alternate-day, 34.1% for consecutive-day A, and 37.7% for consecutive-day B treatments. For MKN45, the RI was 51.1% for alternate-day, 52.2% for consecutive-day A, and 50.5% for consecutive-day B treatments. In vivo, for MKN28, the treated groups showed higher inhibition than the control, and inhibition of tumor growth was higher with alternate-day than with consecutive-day treatment. The RI was significantly higher with alternate-day (49.3%) than with consecutive-day treatment (16.2%; P < 0.05). For MKN45, the RI was greater than 50% in both treated groups. With consecutive-day treatment, 5 of the 14 mice used died during treatment. Leukocyte counts were lower in the mice with consecutive-day than with alternate-day treatment, or control. Atrophic changes and inflammatory cell infiltration of the small intestinal mucosa were severe after consecutive-day, but minimal after alternate-day treatment. CONCLUSION: Experimentally, alternate-day treatment with S-1 is equivalent to consecutive-day treatment in terms of RI of tumor growth, with lower toxicity.

Colorectal carcinoma (CRC) remains the major cause of cancer death in humans. Although chromosomal structural anomaly is presumed to play an important role in the carcinogenesis of CRC, chromosomal copy number alterations (CNA) and loss of heterozygosity (LOH) have not yet been analyzed extensively at high resolution in CRC. Here we aim to identify recurrent CNA and LOH in human CRC with the use of single nucleotide polymorphism-typing microarrays, and to reveal their relevance to clinical outcome. Surgically resected CRC specimens and paired normal mucosa were obtained from a consecutive series of 94 patients with CRC, and both of them were subjected to genotyping with Affymetrix Mapping 50K arrays. CNA and LOH were inferred computationally on every single nucleotide polymorphism site by integrating the array data for paired specimens. Our large dataset reveals recurrent CNA in CRC at chromosomes 7, 8, 13, 18, and 20, and recurrent LOH at chromosomes 1p, 4q, 5q, 8p, 11q, 14q, 15q, 17p, 18, and 22. Frequent uniparental disomy was also identified in chromosomes 8p, 17p, and 18q. Very common CNA and LOH were present at narrow loci of <1 Mbp containing only a few genes. In addition, we revealed a number of novel CNA and LOH that were linked statistically to the prognosis of the patients. The precise and large-scale measurement of CNA and LOH in the CRC genome is efficient for pinpointing prognosis-related genome regions as well as providing a list of unknown genes that are likely to be involved in CRC development.

The genome of a subset of non-small-cell lung cancers (NSCLC) harbors a small inversion within chromosome 2 that gives rise to a transforming fusion gene, EML4-ALK, which encodes an activated protein tyrosine kinase. Although breakpoints within EML4 have been identified in introns 13 and 20, giving rise to variants 1 and 2, respectively, of EML4-ALK, it has remained unclear whether other isoforms of the fusion gene are present in NSCLC cells. We have now screened NSCLC specimens for other in-frame fusion cDNAs that contain both EML4 and ALK sequences. Two slightly different fusion cDNAs in which exon 6 of EML4 was joined to exon 20 of ALK were each identified in two individuals of the cohort. Whereas one cDNA contained only exons 1 to 6 of EML4 (variant 3a), the other also contained an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). The protein encoded by the latter cDNA thus contained an insertion of 11 amino acids between the EML4 and ALK sequences of that encoded by the former. Both variants 3a and 3b of EML4-ALK exhibited marked transforming activity in vitro as well as oncogenic activity in vivo. A lung cancer cell line expressing endogenous variant 3 of EML4-ALK underwent cell death on exposure to a specific inhibitor of ALK catalytic activity. These data increase the frequency of EML4-ALK-positive NSCLC tumors and bolster the clinical relevance of this oncogenic kinase.

The prolonged survival of patients receiving surgery for esophageal cancer has led to an increased incidence of adenocarcinoma arising in the gastric tube used for reconstruction (gastric tube cancer). In patients with advanced gastric tube cancer, resection of the gastric tube should be considered, but currently available procedures are very invasive. In patients undergoing curative surgery for gastric tube cancer that has developed after reconstruction through the retrosternal route, the gastric tube is usually resected through a median sternotomy, followed by reconstruction with the colon. However, postoperative complications often occur and treatment outcomes remain poor. We developed a new surgical technique for gastric tube resection without performing a sternotomy in patients with gastric tube cancer who had previously undergone reconstruction through the retrosternal route. Our technique was used to treat two patients. Two Kirschner wires were passed subcutaneously through the anterior chest; the chest was lifted to extend the retrosternal space and secure an adequate surgical field. The stomach was separated from the surrounding tissue under videoscopic guidance. Total resection of the gastric tube was done. The retrosternal space was used to lift the jejunum. Roux-en-Y reconstruction was performed. Neither patient had suture line failure or surgical site infection. Their recovery was uneventful. Our surgical technique has several potential advantages including (i) reduced surgical stress; (ii) the ability to use the retrosternal space for reconstruction after gastric tube resection; and (iii) a reduced risk of serious infections such as osteomyelitis in patients with suture line failure. Our findings require confirmation by additional studies.

We describe a 30-year-old man in whom upper endoscopy revealed multiple gastric carcinoids. The peripheral blood gastrin level was 2400 ng/ml (normal range, <200 ng/ml). Mucosal biopsy of the gastric body and fundus showed no atrophy; typical type A chronic atrophic gastritis was thus unlikely. Neither abdominal computed tomography nor selective angiography showed any evidence of tumor in the pancreas or at its periphery. However, the possibility of microgastrinoma could not be ruled out. We performed radioguided surgery with a somatostatin analog, diethylenetriamine pentaacetic acid-D-Phe1-octreotide labeled with (111)In (Octreo Scan). The location of the carcinoids was confirmed. Gastrinoma was ruled out. Total gastrectomy was performed, and the gastrin level decreased to the normal range. Macroscopically, 20 carcinoid tumors, measuring 30 mm in maximum diameter, were confirmed. Microscopic examination showed large numbers of endocrine cell micronests. Hyperplasia of parietal cells was observed, suggesting early-stage type A chronic atrophic gastritis. The antrum contained increased numbers of gastrin-positive cells, which probably caused the preoperative hypergastrinemia.

PURPOSE: Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). METHODS: The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. RESULTS: We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. CONCLUSIONS: The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.

Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.

Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers.

Biphenotypic acute leukemia (BAL) is a relatively rare subtype of acute leukemia characterized by the presence of both myeloid and lymphoid cell surface antigens. We have now screened for transforming genes in BAL blasts with the use of the focus formation assay with a retroviral cDNA expression library constructed from malignant blasts isolated from a BAL patient. Some of the retroviral inserts recovered from transformed foci were found to encode wild-type purinergic receptor P2Y, G protein coupled, 8 (P2RY8). The oncogenic potential of P2RY8 was confirmed with the in vitro focus formation assay as well as with an in vivo tumorigenicity assay in nude mice. A variety of luciferase-based reporter assays revealed that P2RY8 increased both the trans-activation activities of CREB and Elk-1 as well as the transcriptional activities of the serum response element and enhancer-promoter fragments of the c-Fos and c-Myc genes. Quantitation of P2RY8 mRNA in CD34(+) cells of bone marrow showed that P2RY8 expression is frequently increased in leukemia patients, especially in those with refractory disease. Our data thus reveal an abundant expression of P2RY8 in leukemic cells and its unexpected role in the pathogenesis of acute leukemia.

BACKGROUND: Many patients with gastric cancer respond to TS-1, but some fail to respond or have recurrence. Second-line therapy is needed. METHODS: We performed a pilot study in patients with advanced gastric cancer who did not respond to TS-1 or who had disease recurrence. The patients received oral doxifluridine (600 mg/day) on days 1 to 21 and an intravenous infusion of paclitaxel (70 mg/m(2)) on days 7, 14, and 21 of a 28-day cycle. The treatment was repeated until disease progression or prohibitive toxicity. Response rate, duration of response, median survival time (MST), effects on pleural effusion, ascites, and other signs, and toxicity were evaluated. RESULTS: The study group comprised 52 patients. The response rate was 28%. The duration of response was 103 days. The MST after the start of second-line treatment was 175 days (95% confidence interval, 135 to 224 days). Pleural effusion or ascites resolved or decreased in 73% of the patients. Hair loss occurred in 32 patients (62%), and leukopenia developed in 28 (54%, grade 3 in 1 patient and grade 2 or lower in the others). The MST after the start of treatment with TS-1 was about 16 months. CONCLUSION: A combination of doxifluridine and weekly paclitaxel is expected to be an effective second-line treatment for gastric cancer not responding to TS-1, especially in patients with malignant ascites or pleural effusion. However, it remains unclear whether paclitaxel plus doxifluridine results in a better response and survival benefit than paclitaxel alone in this subgroup of patients. Further studies are therefore necessary.

To identify transforming genes in acute myeloid leukemia (AML) we here constructed a retroviral cDNA expression library from an AML patient, and then used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid substitutions. The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation.

Background: The development of new surgical instruments and devices has facilitated the performance of esophagojej-unostomy after total gastrectomy. However, total prevention of dehiscence of anastomoses remains difficult. We introduced a new procedure for esophagojejunostomy using a circular stapler, requiring sacrifice of only a small part of the jejunum. Methods: The study group comprised 390 consecutive patients who underwent reconstruction by Roux-en-Y esophagojejunostomy, performed with a circular stapler, sacrificing a small part of the jejunum after total gastrectomy. We assessed anastomotic leakage and anastomotic stenosis after surgery. Results: Only 2 patients (0.5%) had leakage and 4 (1.0%) had anastomotic stenosis after reconstruction. All the patients were cured by conservative therapy. Conclusions: Esophagojejunostomy performed with a circular stapler after total gastrectomy, with sacrifice of only a small part of the jejunum, is a useful and easy procedure, with a leakage rate of 0.5%. Copyright (c) 2007 S. Karger AG, Basel

The patient was a 75-year-old man. Under a diagnosis of angina pectoris, he was being treated with aspirin and ticlopidine hydrochloride at a local clinic. Severe postprandial pharyngeal/thoracic pain and hematemesis occurred. Upper digestive tract endoscopy revealed an extensive submucosal hematoma involving the esophageal orifice and cardia. Computed tomography (CT) scan did not show aortic dissociation or mediastinal emphysema. Antiplatelet therapy was discontinued, and follow-up was continued by fasting and conservative treatment with an H2-blocker. Ten days after onset, endoscopy showed the disappearance of the hematoma, and ingestion was started. Twenty-two days after onset, endoscopy revealed regeneration and cicatrization of the esophageal mucosa. In a detailed examination of heart diseases, angina pectoris was ruled out therefore, antiplatelet therapy was discontinued. There has been no recurrent esophageal submucosal hematoma for 4 years of follow-up. © Japan Esophageal Society and Springer-Verlag 2005.