Yasuhiro Komuro

Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles.

Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion-related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets.

Primary malignant melanoma of the esophagus treated by esophagectomy and adjuvant dendritic-cell therapy

To the Editor: Malignant melanoma is a typical cutaneous tumor, arising from melanocytes. Primary malignant melanoma of the esophagus (PMME) is uncommon, comprising from 0.1% to 0.2% of all malignant esophageal tumors. PMME is characteristically aggressive and disseminates early via the bloodstream and lymphatics.1 Here, we report the first case of surgically treated PMME with adjuvant dendritic-cell (DC) therapy. The patient has been free from any signs of recurrence for 2.5 years after the surgery. A 56-year-old man was investigated because he had vomited blood with clots. Physical examinations revealed no pigmented lesions of the skin, rectum, eyes, or elsewhere that were suspicious for melanoma. Esophagogastroscopy showed an ulcerated tumor, sited 27–32 cm from the incisors (Fig. 1a,b). On the biopsy specimen, the lesion was identified as a malignant melanoma. Computed tomography (CT) showed no evidence of distant metastasis. On July 9, 2001, subtotal esophagectomy and lymph node dissection was performed through a retrosternal route. The patient’s postoperative course was uneventful. The surgical specimen contained an ulcerative tumor, which showed a black area under the normal mucosa on the margin of tumor. Histologically, the tumor cells had invaded to the muscularis propia, and the resection margins were free of tumor. Tumor cells at the edge of the tumor contained abundant melanin granules, and there were melanophages in the matrix (Fig. 2a,b). There was no lymph node metastasis. Immunohistochemical staining was positive for antibodies against S-100 and HMB-45 (Fig. 2c,d) and negative for cytokeratin, findings that were consistent with malignant melanoma. The diagnosis of R0-resected PMME, analogous to a pT2N0M0 stage carcinoma was verified. PMME has extremely high malignant potential, with a mean survival of 14 months after radical resection, and with metastasis or recurrence often being observed even in the early stage.2,3 Therefore, we performed DC therapy as adjuvant therapy. The DC therapy was performed as described previously.4 Briefly, the DC therapy had been approved by the Ethics Committee of the University of Tokyo, and written informed consent was obtained from the patient before the DC therapy was started. DCs were generated from peripheral monocytes collected by leukapheresis. The monocytes were cultured with 1000 IU/ml granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and 500 IU/ml interleukin (IL)-4 for 7 days, with pulsation of autologous tumor lysates. The patient received four intradermal infections, of 3 or 4 107 DCs, weekly. At 2.5 years after the operation, the patient is healthy, without any sign of relapse on chest or abdominal computed tomography, or as shown by tumor markers. The main treatment of PMME is supposed to be surgical resection. However, as stated above, the mean survival after radical resection is 14 months, and the overall 5-year survival rate after radical surgical resection is reported to be 4.2%;1 the efficacy of adjuvant therapy for PMME has never been clearly demonstrated. Therefore, effective adjuvant therapy should be explored, even at a relatively early stage of the disease. The place of chemotherapy and radiotherapy in the treatment of PMME is unclear. However, chemotherapy and radiotherapy alone in the treatment of PMME generally does not show real effectiveness and, thus, it appears that these treatments do not have a major role in the management of this tumor.1 DCs are highly efficient antigen-presenting cells that play a crucial role in the initiation of the T-lymphocyte-dependent specific immune response.5 The clinical usage of autologous DCs in the treatment of cutaneous malignant melanoma, glioblastoma, renal cell carcinoma, prostate cancer, and B-cell lymphoma has been reported, with promising results.6 In particular, in the first trial using DCs, in 16 patients with advanced metastatic melanoma, objective clinical responses were obtained in 5 of the 16 patients, including two complete and three partial remissions.7 No significant side effect has been reported. These reports encouraged us to use DCs as postoperative adjuvant therapy for our patient with PMME, and this brought about a 2.5-year tumor-free period. Our result indicates that DC therapy is a safe and promising approach as adjuvant therapy for PMME, which is often a fatal disease.

Diversion colitis with a mucosal tear on endoscopic insufflation

I read with interest the report of Cruz-Correa and colleagues ( Gut2002;51:600 [OpenUrl][1][FREE Full Text][2] ). They described three cases of collagenous colitis with mucosal tears on endoscopic insufflation and stated that as far as they were aware there were no reports in other gastrointestinal diseases. We would like to present the case of a similar mucosal tear on endoscopic insufflation in a patient with diversion colitis. A 46 year old Japanese man presented with an acute abdomen caused by ascending colon diverticular perforation. He underwent drainage … [1]: {openurl}?query=rft.jtitle%253DGut%26rft.stitle%253DGut%26rft.issn%253D0017-5749%26rft.aulast%253DCruz-Correa%26rft.auinit1%253DM%26rft.volume%253D51%26rft.issue%253D4%26rft.spage%253D600%26rft.epage%253D600%26rft.atitle%253DCollagenous%2Bcolitis%2Bwith%2Bmucosal%2Btears%2Bon%2Bendoscopic%2Binsufflation%253A%2Ba%2Bunique%2Bpresentation%26rft_id%253Dinfo%253Apmid%252F12235088%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=gutjnl&resid=51/4/600&atom=%2Fgutjnl%2F52%2F9%2F1388.atom

A case of adrenal metastasis from rectal carcinoma without lung metastasis : evaluation for alteration of loss of heterozygosity and immunohistochemical expression

1. Ball WP, Baggenstoss AH, Bargen JA. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol 1950;50:345–58. 2. Heikius B, Niemelä S, Lehtola J, Karttunen TJ. Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease. Am J Gastroenterol 1999;94:1062–9. 3. Rasmussen HH, Fonager K, Sorensen HT, Pedersen L, Dahlerup JF, Steffensen FH. Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study. Scand J Gastroenterol 1999;34:199–201. 4. Nakamura S, Nakamura T, Suzuki S. Hepatobiliary and pancreatic complications in patients with ulcerative colitis (in Japanese with English abstract). Nippon Rinsho 1999;57:2549–55. 5. Robert JH, Toledano AE, Toth LS, Premus G, Dreiling DA. Hypovolemic shock, pancreatic blood flow, and pancreatitis. Int J Pancreatol 1988;3:283–92. 6. Collins CE, Cahill MR, Newland AC, Rampton DS. Platelets circulate in an activated state in inflammatory bowel disease. Gastroenterology 1994;106:840–5. 7. Castiella A, Lopez P, Bujanda L, Arriola JA, Alzate LF, Torrado J, et al. Ulcerative colitis associated with acute pancreatitis and platelet aggregates. J Clin Gastroenterol 1996;23:77–8. 8. Haber CJ, Meltzer SJ, Present DH, Korelitz BI. Nature and course of pancreatitis caused by 6-mercaptopurine in the treatment of inflammatory bowel disease. Gastroenterology 1986;91:982–6. 9. Fiorentini MT, Fracchia M, Galatola G, Barlotta A, de la Pierre M. Acute pancreatitis during oral 5-aminosalicylic acid therapy. Dig Dis Sci 1990;35:1180–2. 10. Corey WA, Doebbeling BN, DeJong KJ, Britigan BE. Metronidazoleinduced acute pancreatitis. Rev Infect Dis 1991;13:1213–5. 11. Steinberg WM, Lewis JH. Steroid-induced pancreatitis: does it really exist? Gastroenterology 1981;81:799–808. 12. Schrier RW, Bulger RJ. Steroid-induced pancreatitis. JAMA 1965; 194:564–5. 13. Schwarz M, Thomsen J, Meyer H, Boehler MW, Beger HG. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery (St Louis) 2000;127:427–32.

Acute acalculous cholecystitis with a decrease in CD4/CD8 ratio

Acute acalculous cholecystitis (AAC) usually occurs in the elderly and in those with severe preexisting pathological conditions. However, there have recently been reports of AAC in relatively young immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). We report here a 27-year-old woman with AAC who received an emergent cholecystectomy. Although anti-human immunodeficiency virus antibody (anti-HIV) was not detected, a decrease in the CD4/CD8 ratio in sera was found. This rare case of AAC in a patient with decreased CD4/CD8 ratio who showed no other related diseases suggests that surgeons should keep in mind the possible presence of immunosuppression in this condition.

Chemoradiotherapy for rectal cancer: current status and perspectives

The radiotherapy used for rectal cancer is commonly adjuvant or neoadjuvant therapy, or therapy for nonresectable disease, such as highly advanced or recurrent cancers. Previous reports have shown that radiotherapy is effective for reducing local recurrence rates, as well as survival rates, after surgery for rectal cancer. In terms of surgical technique, lateral node dissection has been widely performed in Japan to reduce the local recurrence rate in the surgical treatment of rectal cancer. On the other hand, a number of reports from Western countries suggest that total mesorectal excision (TME) combined with radiotherapy is effective in reducing local recurrence in rectal cancer. Recently, a randomized controlled trial to investigate combined therapy of TME with radiotherapy has reported its results. In the present review, we discuss the effectiveness of radiotherapy and chemoradiotherapy as adjuvant or neoadjuvant therapy for the treatment of patients with surgically resected rectal cancer.

Weight loss and an abdominal mass after resection of a lung carcinoma

A 47 year old man underwent a right upper lobectomy with resection of the chest wall for pleomorphic carcinoma of the lung in July 2003. In January 2004, he had abdominal pain and anorexia. Gastrointestinal endoscopy showed no …