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We report herein the case of a 57-year-old female who was admitted to our hospital for treatment of rectal carcinoma and incidentally found to have a giant cystic tumor, 20 cm in diameter, in the body and tail of the pancreas. Several imaging procedures, including ultrasonography, computed tomography, and magnetic resonance imaging, showed that this tumor was round and hypovascular, and had a septum with protuberant lesions. The capsule was 3-4 mm thick with partial calcification. A preoperative diagnosis of a solid cystic tumor (SCT) of the pancreas was made, even though these tumors are rarely found in females in their fifties. Moreover, few reports of SCT with a septum have been described. Distal pancreatectomy and splenectomy were performed, and the tumor was found to be filled with massive necrotic tissue. Microscopically, the tumor was confirmed to be a SCT with a fibrous septum. We present this case due to the atypical findings, including the age of the patient and the existence of a septum caused by extracapsular growth.

A technique, by which the root of the right gastric artery can be clearly exposed and the area of the right gastric artery can thus be completely dissected, is presented herein. In conventional procedures, the approach to the right gastric artery is performed from the lesser omentum, and a lymphadenectomy along the common hepatic artery is carried out after the division of the right gastric artery. Using the present technique, the common hepatic artery is exposed before the exposure of the right gastric artery and lymph node dissection is thus continued peripherally to the proper hepatic artery. During these procedures, the root of the right gastric artery arising from the hepatic artery can be easily identified. The lymphatic flow from the area of the right gastric artery to that of the common hepatic artery is transected using the conventional procedure, but not with the present technique. In addition, an en bloc dissection of the regional lymph nodes is also possible when using this procedure.

Most complications after appendectomy occur within 10 days; however, we report herein the unusual case of a patient in whom a wound abscess was detected more than 10 years after an appendectomy. A 26-year-old woman presented to our hospital with nausea and vomiting, pain, and a mass in the right lower abdominal wall. She had undergone an appendectomy 11 years previously. Physical examination revealed a tender mass, 5 cm in diameter, under the appendectomy scar. An abdominal ultrasonography demonstrated a low-echoic mass lesion measuring 9.0 x 5.0 x 2.0 cm. Incision of the connective tissue revealed about 3 ml of cream-colored and odorless fluid in the abscess cavity. Fistulography revealed an abscess cavity not communicating with the bowel lumen. Floss was discovered in the connective tissue and removed. Debridement of the abscess wall was performed and a piece of the wall was sent for histologic examination. Pathological examination revealed panniculitis of the subcutaneous tissue, and panniculitis with granulation and granuloma of the abscess wall. This case report demonstrates that a preoperative diagnosis should be based not on one finding, but on all findings collected, inclusively.

Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of beta1 and beta2 integrins on these lymphocytes quantitatively with two-color flow cytometry. Both LPL and TIL expressed a lower level of common beta1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated alpha chains, the expression levels of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher, whereas those of alpha4 (CD49d) and alpha6 (CD49f) were markedly reduced in LPL and TIL. No significant differences were observed in expressions of any alpha1 integrin chains between these two lymphocytes populations. Similarly, both alphaL (CD11a) and beta2 (CD18) were down-regulated in TIL and LPL with CD8+ cytotoxic phenotype, but not in those with CD4+ phenotype. CD8+ TIL expressed a slightly but significantly higher level of alphaLbeta2 than did CD8+ LPL. CD8+ LPL and CD8+ TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8+ PBL. Although CD8+ TIL showed a slightly higher level of adhesion to these substrates than did CD8+ LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.

The purpose of this investigation was to evaluate the effects of GH and IGF-I administration in a murine model of burn-induced gut-derived sepsis. BALB/C mice were treated with 4.8 mg/kg/day of GH, 24 mg/kg/day of IGF-I or saline for 4 days. They were then administered 1010 E. coli by gavage and subjected to 20% full thickness flame burn. All mice received allogeneic blood transfusion 5 days before burn injury to induce mild immunosuppression. Seventy-three mice were observed for survival and 51 mice were sacrificed at 4 and 20 h postburn. Blood, mesenteric lymph nodes (MLN), spleen and liver were harvested aseptically, and viable bacterial counts in the organs were determined. The small intestine was harvested for the evaluation of villus height and mitoses in the crypts. GH and IGF-I groups showed a significantly better survival than the control group. GH and IGF-I groups had significantly greater villus height and mitoses/crypt than the control group. Translocation of bacteria was not significantly different among groups, however, the relation between the numbers of viable bacteria in MLN and blood suggests that both GH and IGF-I reduced systemic spread of translocated bacteria. It is concluded that GH and IGF-I had positive effects on outcome in this model of burn-induced gut-derived sepsis. It appears that GH and IGF-I may have immune-enhancing effects and that administration of these agents may be useful for burn injury.

Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta1 and beta2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated alpha chains, the expressions of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha4 (CD49d) and alpha6 (CD49f) were markedly downregulated in TIL. Both alphaL (CD11a) and beta2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.

We report a rare case of ulcerative colitis (UC) associated with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in multiple organs, and with compressive fracture from osteoporosis after the administration of high-dose prednisolone and azathioprine. A 25-year-old man had been treated with high-dose prednisolone for UC. He suddenly experienced severe lumbago, which prevented him from walking. Plain X-ray demonstrated compressive fractures of the thoracic and the lumbar vertebrae, which were thought to be due to osteoporosis as a side effect of the high-dose prednisolone. At this admission, in another hospital, he also had a bloody discharge from the rectum, and azathioprine was started; however, the patient's condition still did not show any improvement. The total doses of azathioprine and prednisolone he had received were 3150 mg and more than 15 000 mg, respectively. Considering the presence of the serious complications, surgical intervention was the treatment selected. Culture study revealed MRSA in the feces and nasal cavity, and P. aeruginosa in the feces and urine. Vancomycin hydrochloride and gentamicin were administered, and were effective, with a subsequent negative culture study. Subtotal colectomy with mucus fistula was performed. After the operation, culture studies remained negative. Major steroid side effects such as bone fracture and osteoporosis should be considered as an indication for surgery in UC patients. MRSA and P. aeruginosa are a menace, especially for UC immunosuppressed patients on steroid or immunosuppressive therapy. When these bacteria are detected, there should be prompt and adequate antimicrobial therapy against the organisms and the immunosuppressive therapy should be immediately discontinued. We conclude that surgical therapy should be considered in the earlier stage for patients with intractable UC, rather than continuing long-term administration of steroid or azathioprine, which may lead to serious complications.

Background: Laparoscopic technique has been applied to a variety of colonic and rectal operations, generally using carbon dioxide insufflation (CDI). However, CDI is inevitably associated with cardiopulmonary loading and can cause complications. The objective of this study was to determine the feasibility of gasless laparoscopic colonic surgery. Methods: The abdominal wall was lifted up using an originally designed retractor. A small incision, 3 to 5 cm in length, was made at the start of the operation. The surgeon operated through this incision using both conventional and laparoscopic instruments. Results: Operations were undertaken in 67 patients. In 6 patients (9%), conversion to open surgery was necessitated. In the remaining 61 patients, operations were completed with gasless laparoscopically assisted technique. Four reoperations (7%) were performed because of postoperative bleeding, anastomotic rotation, anastomotic stricture, and transmesenteric hernia. Fifty-three patients with colonic cancer were operated on with potentially curative intent. Of these, 1 (2%) developed hepatic recurrence during the mean follow-up period of 23.8 months. There was no port site recurrence. Conclusions: Gasless laparoscopic colonic surgery is technically feasible. CDI is not necessary to perform minimal access surgery.

The transcription factor IRF-1 has been implicated in tumor suppression: IRF-1 suppresses cell transformation and mediates apoptosis in vitro. Here we show that the loss of IRF-1 alleles per se has no effect on spontaneous tumor development in the mouse but dramatically exacerbates previous tumor predispositions caused by the c-Ha-ras transgene or by nullizygosity for p53. Grossly altered tumor spectrum, as compared to p53-null mice, was also observed in mice lacking both IRF-1 and p53, and cells from these mice show significantly higher mutation rate. Our results suggest that IRF-1 is a new member of the tumor susceptibility genes.

Background The frequency of lymph node metastasis in mucosal gastric cancers 2–4 cm in diameter was low (three (1·3 per cent) of 234) in patients treated in this unit between 1966 and 1995. This study was a prospective report on local resection with lymphadenectomy for early gastric cancer. Methods Eight patients with a single early gastric cancer underwent local resection with lymphadenectomy. The tumour was excised with a non-cancerous rim of approximately 2 cm. The extent of lymphadenectomy depended on tumour location. Intraoperative endoscopic examination and frozen-section analysis of the dissected nodes were used to determine the resection line and evaluate nodal status. Results Mean operating time, blood loss and number of dissected nodes were 171 min, 87 ml and 8 respectively. There were no operative complications. Cancer invasion was confined to the mucosa in six tumours but two patients had minute submucosal invasion. The maximum diameter of the resected specimens was 10 cm and no nodal involvement was detected. No patient developed postgastrectomy syndrome. Conclusion For selected patients with early gastric cancer, local resection with lymphadenectomy can provide a good quality of life without compromising cure rate.

We herein describe a 27-year-old male presenting with a pulmonary blastoma. The patient was admitted to our hospital with the chief complaints of fever and left back pain. Chest roentgenograms showed a tumor measuring 10 cm in diameter in a lower lobe of the left lung. Computed tomography and magnetic resonance imaging revealed a well demarcated and heterogeneously enhanced tumor. Although a histological diagnosis could not be obtained by a transbronchial biopsy, image analyses led us to suspect it to be malignant. The patient underwent a left lower lobectomy with lymph node dissection. A histopathological examination revealed the tumor to be a biphasic type of pulmonary blastoma. Because of the rapid progress of the tumor and the difficulty in making a preoperative diagnosis in such cases, an immediate surgical resection is therefore recommended in cases with even the slightest suspicion of malignancy.

OBJECTIVE: We aimed to present new histopathological features of metastatic liver nodules as more reliable prognostic factors after surgical resection for colorectal metastatic cancer. METHODS: Clinicopathological features, including newly proposed histopathological ones, of 63 consecutive patients were reviewed retrospectively to determine which most strongly correlated with long-term prognosis after hepatectomy for metastatic tumors from colorectal cancers, using univariate and multivariate analysis. RESULTS: The 1-, 3-, and 5-year cancer-related survival rates after hepatectomy were 87.8%, 55.2%, and 47.3%, respectively. New histopathological features we proposed, which are expansive growth, marginal fibrosis, and peritumorous lymphocytic infiltration of hepatic tumor, were significant prognostic factors for cancer-related survival after hepatectomy in an univariate analysis. Also in a multivariate analysis, i.e., a stepwise Cox regression analysis, infiltrative, i.e., not expansive, growth of hepatic tumor was one of significant and independent poor prognostic factors for survival after hepatectomy, with moderate to severe lymphatic vessel involvement of the primary colorectal lesion, microscopic cancer invasion at the surgical margin of hepatectomy, and extrahepatic distant metastases. CONCLUSIONS: Our results suggest that our proposed new histopathological features of hepatic metastases were good predictors of prognosis after surgical resection for hepatic metastases from colorectal cancer. Especially, infiltrative growth of hepatic tumor is strongly correlated with a poor prognosis after hepatectomy.

It has been established that lymphocytes obtained from tumor-draining lymph nodes (DLN) are sensitized to the tumor antigen in vivo. Moreover, after being activated in vitro, these cells can be utilized for adoptive immunotherapy. In the present study, DLN cells, obtained from C57BL/6 mice with fibrosarcoma (MC-1), were activated and expanded with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2 (rIL-2). These CD4- CD8+ CD25+ CD44+ T-cells showed specific antitumor efficacy to the pulmonary micrometastases of an autologous tumor, against which lymphokine-activated killer cells were ineffective; however, they did not show cytolytic activity in vitro. The supernatant, obtained by coculturing the activated DLN cells with MC-1 cells, exhibited the specific production of interferon-gamma (IFN-gamma) which was enhanced by rIL-2. The therapeutic effect of the activated DLN cells correlated with the specific IFN-gamma production better than with the cytolytic activity.

Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a multifactorial disorder with significant genetic influence. Recently, evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3 was reported by an affected sib-pair analysis. Previous reports indicate a possible mucin abnormality in UC patients, but whether genetic differences in a specific mucin gene are associated with UC is unknown. Here we analysed polymorphisms of variable number of tandem repeats (VNTRs) within this gene using DNAs obtained from 243 Japanese (75 patients with UC and 168 controls), and to confirm the result we undertook a two-stage examination using 328 Caucasian samples (72 and 85 with UC in the first and second stages, respectively, and 171 controls). When the frequency of patients carrying one or two rare VNTR alleles was compared with that of controls, a significant increase was found first in Japanese patients (odds ratio 2.72, 95% CI 1.17-6.32, P = 0. 0308). In Caucasians, the odds ratio was 2.80 (95% CI 1.36-5.75, P = 0.0079) in the first stage, 2.43 (95% CI 1.20-4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P = 0.0024) in total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P = 0.0001). This result suggests that rare alleles of the MUC3 gene may confer genetic predisposition to UC.

Background. Neutrophils contribute to the host defense mechanism, but they can cause remote organ injury in peritonitis. The purpose of this study was to examine neutrophil adhesion to the peritoneum and remote organs simultaneously in peritonitis using a fluorescence microscopic method. Study design. Experiment 1: Sprague–Dawley rats ( n = 16) were injected intraperitoneally (ip) with saline solution or 10 5 , 10 7 , or 10 9 Escherichia coli. Five hours after challenge, 1 × 10 6 fluorescein-labeled neutrophils were infused. Two minutes after neutrophil injection, five peritoneal samples (the greater omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Lung myeloperoxidase (MPO) activity was also determined. Experiment 2: Rats ( n = 23) were given 10 9 E. coli ip. Before challenge (0 h) or at 1, 5, or 10 h after challenge, labeled neutrophils were infused. Then, the labeled neutrophil numbers in organs and lung MPO activities were assessed as described for Experiment 1. Hemodynamic and arterial blood gas data were also obtained in another set of rats before and at 1, 5, 8 and 10 h after 10 9 E. coli ip challenge. Results. Experiment 1: The labeled neutrophil numbers in the peritoneum, lungs, and kidney showed significant positive correlations with the injected bacterial numbers. Lung MPO also positively correlated with E. coli number and labeled neutrophil number in the lungs. Experiment 2: Labeled neutrophil numbers in the peritoneum and kidney peaked at 5 h. The pulmonary labeled neutrophil number rose, reaching a plateau at 5 h. No remarkable change was observed in the hepatic labeled neutrophil number. There was a positive correlation between lung MPO activity and pulmonary labeled neutrophil number. Hemodynamic and blood gas data reflected a hyperdynamic state. Conclusions. Concomitant dose-dependent increases in neutrophil adhesion in the peritoneum, lungs, and kidney were observed in this peritonitis model. Increased neutrophil adhesion was transient in the peritoneum and kidney but persistent in the lungs. Strategies modulating neutrophil adhesion in organs are anticipated to be useful for the treatment of peritonitis.

We developed a new bioreactor for a bioartificial liver filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF) and in our previous study showed that this NWF bioreactor has promising in vitro efficiency. In the present study, we investigated the efficacy of the NWF bioreactor in a direct hemoperfusion experiment conducted to treat pigs with liver failure. Porcine hepatocytes were isolated from the whole liver of a Sangen strain pig. They were immobilized in a 200 ml column containing NWF via perfusion in a closed circuit for 24 h to prepare a NWF bioreactor. The following day an operative liver failure model was produced by creating a portocaval shunt and ligating the entire hepatoduodenal ligament in the porta hepatis. Perfusion treatment was initiated 4 h after operative induction of liver failure and continued for about 1 h. The pigs which underwent perfusion treatment showed significant improvements in survival and blood data, including ammonia, total bile acid, glucose, and prothrombin time, attributed to significant improvements in the post- as compared to the pre-bioreactor levels in the perfused blood of the treated pigs. These beneficial effects of the NWF bioreactor were based on its excellent composition which allows the accommodation of adequate numbers of hepatocytes and direct contact between hepatocytes and perfused blood.

We present an autopsy case of an 83-year-old Japanese man with a mucin-producing adenocarcinoma accompanied by pancreatolithiasis in the head of the pancreas. He suffered from obstructive jaundice and died of disseminated intravascular coagulation. He did not normally drink alcohol and had no history of chronic pancreatitis. The autopsy findings revealed a mucinous cystic tumor, composed of multiple dilatated branches, in the head of the pancreas. Histological examinations showed papillary adenocarcinoma, which scirrhously infiltrated the distal common bile duct with perineural invasion and lymph node involvement. He was thus diagnosed to have mucin-producing branch-type cancer in the head of the pancreas. The main pancreatic duct was dilated, and the residual pancreatic tissue showed moderate fibrosis and parenchymal atrophy. A stone was observed in a dilated branch of the primary lesion. To the best of our knowledge, there have only been five previously reported cases of mucin-producing tumor associated with pancreatolithiasis. Intraductal calcification is a major characteristic of chronic pancreatitis, but it is clinically important not to misdiagnose cancers associated with pancreatolithiasis such as chronic pancreatitis.

Exposure of cells to extremely low frequency (ELF) electromagnetic fields which reportedly induced the transcription of heat shock protein 70 (HSP70) 1,2, was recently reputed by other studies. HSP is a group of proteins produced by cells in response to stress. We hypothesized that repetitive pulse magnetic stimulation, a much stronger electromagnetic stimuli than those used in the past studies, could induce the stress response of cells.

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.

Background: Several researchers reported promising results that local excision with or without postoperative chemo-radiation therapy is an alternative approach for sphincter preservation in patients with locally invasive rectal carcinomas. However, indications and long-term results have not yet been determined. Methods: Demographic and pathological characteristics of eight patients with locally invasive tumorsundergoing initially local excision were reviewed with reference to histological features at the invasive margin. Results: All the tumors were well differentiated adenocarcinomas. In all but two tumors, the invasion was limited within the proper muscle layer. Radiation therapy was givenpreoperatively in one patient and postoperatively in two patients. Additional bowel resection was not attempted in thesethree cases. Among the remaining five patients, two received additional bowel resection with lymph node dissection. No lymph node metastasis was observed in these two patients. During the average follow-up period of 55 months, three patients had regional lymph node metastases at 7,36 and 72 months, respectively. Another patient had regional lymph node and distant metastases at 5 months. Three out of five patients with moderate to severe grade of dedifferentiated histology at the invasive margin (H-inv) hadregional lymph node metastases. On the other hand, one out of three patients with mild H-inv had lymph node metastases. Conclusions: H-inv may be useful as a clinical predictor of lymph node metastasis. However, more experience is needed to confirm the usefulness of H-invin selecting invasive rectal cancer patients in whom local excision is safe and appropriate.

Background: Growth hormone (GH) regulates the immune and metabolic systems; however, the effects of GH on the functions and cell death of polymorphonuclear neutrophils (PMNs) are not well understood. Therefore, this study was designed to investigate the effects of GH on PMN apoptosis, reactive oxygen intermediates (ROI) production, CD16, and Fas expression. We also investigated the effects of GH on the functions of other circulating leukocytes (ie, monocytes and lymphocytes). Methods: Venous blood was collected from healthy volunteers. Whole blood was washed and pretreated with GH (0 or 100 ng/mL) for 3 hours and then cultured for 0, 4, or 12 hours. PMNs in washed whole blood were analyzed by flow cytometry for cell death, phorbol myristate acetate-stimulated ROI production, CD16, and Fas expression at each time point. Morphologic features also were assessed. PMN apoptosis was confirmed by chromatin staining and DNA gel electrophoresis. Results: GH inhibited PMN apoptosis at 12 hours of culture. GH enhanced ROI production by PMNs and monocytes throughout the 12-hour culture but had no effects on CD16 expression on PMNs. Furthermore, GH decreased Fas expression on PMNs at 4 hours of culture. However, there were no effects of GH on apoptosis of monocytes or lymphocytes for the duration of this experiment. Conclusions: GH pretreatment down-regulates Fas expression on PMNs, inhibits apoptosis, and up-regulates ROI production. GH pretreatment also increases monocyte ROI production. Although activated PMNs have potentially harmful aspects, our results suggest that GH may improve host defense, mainly through enhancement of the PMN functional life span.

Loss of heterozygosity (LOH) observed in human tumors strongly suggests the existence of (a) tumor-suppressor gene(s) at the concerned locus. A series of studies has revealed that LOH on the long arm of chromosome 5 (5q) frequently occurs in differentiated gastric adenocarcinomas. Furthermore, it has been shown that the interferon regulatory factor-1 (IRF-1) locus on chromosome 5q31.1 is one of the common minimal regions of LOH in these cancers. IRF-1 is a transcriptional activator that shows tumor-suppressor activity in the mouse. In the present study, we examined the sequence of the IRF-1 gene in 9 cases of histologically differentiated gastric adenocarcinomas, all of which exhibited LOH at the IRF-1 locus. We identified a mis-sense mutation in the residual allele in one case. This mutated form of IRF-1 showed markedly reduced transcriptional activity. In addition, overexpression of wild-type IRF-1 induced cell-cycle arrest, whereas such activity was attenuated in the mutant IRF-1. These results suggest that the loss of functional IRF-1 is critical for the development of human gastric cancers.

CD27, a member of the tumor necrosis factor (TNF) receptor family, has been implicated in T cell activation, T cell development and T-dependent antibody production by B cells. Its ligand CD70 has been identified only in humans, and, thus, physiological and pathological roles of the CD70-CD27 interaction remain to be determined in an experimental animal system. In the present study, we identified murine (m) CD70 by molecular cloning, and characterized its expression and function by generating an anti-mCD70 mAb. The mCD70 cDNA encoded a type II transmembrane glycoprotein of the TNF family, having 56.5% identity to the human CD70 amino acid sequence. The mCd70 gene was assigned in the central region of chromosome 17. To explore the expression and function of mCD70, we generated cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein (mCD27-Ig) to mCD70 transfectants. FR70, as well as mCD27-Ig, immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70 far more efficiently than mCD27-Ig. FR70 also abrogated the CD28-independent co-stimulatory activity of A20 cells. The expression of mCD70 was detected on splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti-IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced mCD70 expression on splenic B cells. These results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system. FR70 will be useful for further investigating the physiological and pathological roles of the CD70-CD27 interaction in T cell development, T-dependent antibody production and various disease models in the murine system.

Background: The biological behavior of signet-ring cell carcinomas in colorectum tends to beworse than thatof mucinous carcinomas. However, inprevious studies, clinicopatho­ logical features of this disease have been somewhat ill-defined because various histological criteria of this disease were adopted. Methods: We selected 11 cases of signet-ring cell carcinomas and 29 cases of mucinous carcinomas among 1595 consecutive colorectal carcinomas ondefined criteria and compared clinicopathological and molecular biological features between these twotypes ofcarcinomas. Results: Clinical stagings of signet-ring cell carcinomas were far advanced and their prognosis tended to be worse than that of mucinous carcinomas. Furthermore, the incidence of K-ras mutations in signet-ring cell and mucinous carcinomas showed no difference between these two types of carcinomas. However, the incidence of K-ras mutation in these diseases was slightly lower than that in 30 ordinary colorectal carcinomas examined as a comparison. Conclusions: These results suggest that the carcinogenesis of signet-ring cell and mucinous carcinomas are different from that of ordinary colorectal carcinomas and that there may exist othergenes related to malignancy of signet-ring cell carcinomas.

Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert different effects on the colon in terms of promotion or inhibition of tumor development. Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformation of colonic cells. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to compare the effects of PUFAs on the proliferation of non-malignant and malignant cells. We also determined the cellular utilization of fatty acids in media by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed at media concentrations ranging from 10 to 20 microg/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 microg/ml, which had no effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC transformants than in NIH3T3 cells (P0.05). There was no difference in the utilization of fatty acids between the two cell lines cultured in media supplemented with ARA. We conclude that the cellular response to exogenous long-chain PUFAs is modified during the course of malignant transformation, and that EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(−) tumors were radioresistant, and the majority of p53(−) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(−), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(−) group (P

Objective: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. Design: Prospective randomized experimental study. Setting: Research laboratory in a university hospital. Subjects: Balb/c mice (n = 21). Interventions: Mice were challenged intraperitoneally with 1 x108 Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. Measurements and Main Results: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. Conclusions: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils. (Crit Care Med 1998; 26:338-343) Postoperative septic complications are the most frequent complications in patients undergoing major surgery [1]. Moreover, these complications often occur in patients with malnutrition [2,3], particularly those patients with gastrointestinal disorders [4], or the elderly [5,6]. Therefore, it is important to recognize patients at risk for septic complications preoperatively, and to prophylactically reduce the frequency rate and severity of such disorders, as well as to manage them after the onset. Growth hormone (GH) and insulinlike growth factor I (IGF-I) have been used in catabolic states because of their anabolic properties [7-9]. In addition, these hormones have several immunomodulatory effects [10-13]. Low serum/plasma GH and IGF-I concentrations have been demonstrated in aged populations [14], and low plasma IGF-I concentrations are also related to malnourished states [15,16], with both age and malnutrition increasing the risk of septic complications, as mentioned above. In such patients, therefore, prophylaxis with GH or IGF-I may effectively prevent postoperative septic complications. Ziegler and Leader [17] also mentioned the ICU patient groups as at risk for infection (e.g., severe catabolic illness, malnourished patients hospitalized with catabolic illness or injury, or elderly patients requiring major operations), in whom it would be worthwhile to determine whether GH improves immune cell function and/or reduces the frequency rate or severity of infection. Among septic complications, we focused on severe peritonitis, which has a high mortality rate despite recent improvements in surgical management [18,19]. In peritonitis, host defense mechanisms may be improved by enhancing the bactericidal activities of peritoneal phagocytes (macrophages and neutrophils), which represent the first line of host defense [20]. On the other hand, activated neutrophils in remote organs can cause tissue injury [21,22]. Therefore, new prophylactic strategies may require the control of phagocyte exudation and modulation of the activities of local and systemic phagocytes in severe bacterial peritonitis. Surface opsonin receptors play critical roles in the recruitment and activation of phagocytes. CD11b (alpha M subunit of Mac-1, complement receptor 3) is involved in iC3b binding, phagocytosis and reactive oxygen production, in addition to the neutrophilendothelium binding essential to neutrophil exudation [23-25]. CD32 and CD16 (immunoglobulin G [IgG] Fc receptors II and III, respectively) are also involved in activating phagocytosis and the bactericidal activity of phagocytes [26,27]. Therefore, it may be worthwhile to focus on the expression of these opsonin receptors on local and systemic phagocytes to devise strategies for preventing severe bacterial peritonitis. We [28] previously showed that GH and IGF-I pretreatments enhanced host defense and prolonged the survival of mice with lethal peritonitis. In that study [28], both hormones, especially GH, markedly reduced peritoneal bacterial counts with increased numbers of peritoneal exudative cells (PECs) at 4 hrs after the onset of peritonitis. The aim of the present study was to investigate the mechanisms of peritoneal bacterial reduction with enhanced phagocyte exudation, at the 4-hr time point, by GH and/or IGF-I pretreatments. We focused on CD11b and CD32/CD16 expression on local and systemic phagocytes in the same murine peritonitis model.

Immunochemical methods were developed for the optimal detection and characterization of total cellular p53 protein expression, both in the nuclear-attached and soluble fractions of colorectal cancers, in order to improve the correlation between protein deregulation and gene status. Seventy colorectal carcinomas were studied using 3 monoclonal antibodies in a sensitive analyzing system combining flow cytometry (nuclear-bound fraction) and enzyme-linked immunosorbent assay (ELISA; soluble fraction). DNA indices were calculated on the DNA histograms and mutations of the p53 gene were searched for in a subset of 41 cases. Three p53 expression patterns were found: 35 tumors were classified as pattern "A," characterized by high p53 expression including "mutant" conformation and missense mutations of the gene (16/17 cases tested), pattern "B" consisted of 15 tumors with total absence of p53 expression corresponding to nonsense mutations of the gene (8/9 cases tested), and pattern "C" of 20 tumors presenting low or undetectable nuclear-bound p53 but intermediate p53 protein content (pAb (1801+) in the soluble fraction. The latter pattern was associated with wild-type genes (14/15 cases tested), and with tumors that were often localized in the right colon compared to pattern "A" and "B" tumors (45% versus 8%, P < 0.009) and were frequently near-diploid (80% versus 29%, P < 0.0002). No correlation was found between tumor stage and the patterns of p53 expression. The results indicate that both flow cytometry (FCM) and ELISA seem necessary for the proper characterization of the p53 expression pattern, thus achieving a high degree of concordance with molecular analysis of gene mutations.

In establishing an effective therapy for cancer, one of the most important issues to be considered is how to target only cancer cells and to protect the surrounding normal tissues from side effects. For the targeted gene therapy of cancer, we have been developing our strategies according to these two approaches: 1) specific gene delivery to cancer cells via cancer-specific antigens, and 2) specific gene expression in cancer cells by cancer-specific promoters. Here, I focus on the first approach, developing Carcinoembryonic antigen (CEA)-targeting strategy by retrovirus displaying a chimeric envelope protein with anti-CEA single chain variable fragment (scFv) antibody. Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy.

A bioartificial liver system (BAL) is expected to become an effective treatment for patients with acute liver failure or for patients waiting for liver transplantation. Four groups have already performed actual human clinical trials. However, except for the trial by Rozga et al. [1], the life-saving effect was not so significant. Thus, along with increase in immobilized cell numbers (up to 2X1010 cells, 10% of whole human liver cells), enhancement in cellular functional capacity is still required. The present requirement from the clinical sides of the BAL system is very simple, that is, it should function only up to 6 hour’s plasma perfusion and should be disposable in order to avoid acute immuno-rejection reaction [1]. Therefore, maximal metabolic performance even in the short term is a crucial subject. In this study, we have developed a prototype of a new BAL module immobilizing 2.5% of human liver cells, based on the suspension perfusion culture of porcine hepatocyte spheroids.

Tob (Transducer of ErbB-2) is a newly identified tumor suppressor that may interact/interfare with protein tyrosine kinase receptors including ErbB-2 [1]. ErbB-2 phosphorylates and interacts with Shc that participates inbetween active tyrosine protein kinases to Ras signaling pathway. A point mutation or an elevated expression of ErbB-2 results in oncogenic growth of cells.

Objective: To clarify how antibiotic prophylaxis influenced an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) and postoperative infection. Design: Retrospective review. Setting: University-affiliated teaching hospital. Patients: All patients (n = 1824) undergoing subtotal esophagectomy, gastrectomy, or colorectal surgery during the period 1982 through 1995. Main Outcome Measures: Type, timing, and duration of prophylactic antibiotics. Postoperative infection by the Centers for Disease Control and Prevention definition and the organisms isolated. Results: Third-generation cephalosporins were frequently administered for prophylaxis during the period 1982 through 1990. The rate of isolates of MRSA from the infected site increased, peaking in 1988 to 1990. Since 1991 to 1992, along with a marked decrease in third-generation cephalosporin use, the rates of MRSA isolated have declined dramatically. The timing of administration changed from postoperative to intraoperative. Although the duration was gradually decreased, coverage was still provided until about the fifth postoperative day, even during 1993 to 1995. Prolonged coverage did not reduce the rate of superficial incisional or organ/space surgical site infection or that of pneumonia. Conclusions: Overuse of third-generation cephalosporins for long periods caused an MRSA outbreak. Long-term prophylaxis did not lower infection rates. The briefest possible prophylaxis with first- or second-generation cephalosporins should be used in general surgery. Arch Surg. 1997;132:1320-1325

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.

PURPOSE: In view of the changing concept of colorectal carcinogenesis during the last 20 years, a historical review of colorectal carcinogenesis is presented. METHODS: The changing concept of colorectal carcinogenesis was presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neoplasms ; 4) carcinogenesis based on molecular biology. RESULTS : In the first period, large adenomas were thought to play the most important role as precursors to colorectal carcinomas; however, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on the new precursor of colorectal carcinomas that were not recognized in the past. Molecular biology clarified a lack of K-ras mutation in nonpolypoid, particularly depressed, neoplasms, suggesting the presence of a novel pathway of colorectal carcinogenesis, different from that in polypoid neoplasms. CONCLUSIONS: The concept referred to as the adenoma-carcinoma sequence changed because colonoscopic polypectomy specimens were studied, and rather small, nonpedunculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolypoid neoplasms provides us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms, and genetic alterations in so-called de novo carcinomas need to be clarified.

A 54-year-old woman was admitted to our department for assessment of a tumor of the pancreas found incidentally on abdominal ultrasonography. Examination revealed a hypovascular 1-cm sized tumor in the body of the pancreas. Surgical examination revealed that the tumor was solitary and located in the pancreas body, with no invasion to the adjacent organs iof lymph node involvement. Distal pancreatectomy, preserving the spleen, was performed. Histologically, the tumor was a glucagonoma with evident ductular and tubular structures, suggesting that its site of origin was ductal epithelia.

The treatment of patients with thoracic esophageal cancer invading adjacent organs is controversial. The effect, on survival, of esophagectomy with regional node dissection after combined chemotherapy and radiotherapy was studied in six patients with the esophageal cancer. Two patients undergoing esophagectomy survived > 39 months without relapse. Postoperative complications were not observed in patients undergoing esophagectomy with a two-step surgical procedure (interval of several weeks between esophagectomy and reconstruction), while complications were observed in all patients undergoing a one-stage surgical procedure. Two-step esophagectomy with regional node dissection after combined chemo- and radiotherapy is a promising option for patients with esophageal cancer invading adjacent organs.

Background/Aims: Ubiquitin covalently attaches to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tumors. To clarify the change in protein metabolism during hepatocarcinogenesis, we studied ubiquitin immunoreactivity in hepatocellular carcinomas (HCCs) and precancerous lesions using immunohistochemistry and immunoblot analysis. Methods: A total of 72 HCCs (37 advanced, 19 early, 16 early-advanced (advanced HCC component in early HCC nodule) type HCCs) and 18 precancerous lesions (8 atypical adenomatous hyperplasias (AAHs), 10 adenomatous hyperplasias (AHs)) were studied immunohistochemically. Immunoblot analysis was also performed in advanced HCC and early HCC cases. Results: Non-tumorous hepatocytes were either immunonegative or weakly stained in their nuclei. Advanced HCCs showed strong immunoreactivity in most cases, while early HCCs showed relatively weaker immunoreactivity. In 14 to 16 early-advanced type tumors, the inner portion of the nodules, which corresponds to advanced HCC, showed stronger immunoreactivity than the outer low-grade portion. In 8 of 8 AAHs and 7 of 10 AHS, positive but weak staining was found. Immunoblot analysis showed an increase in 42 kDa ubiquitinated protein(s) in 8 of 16 advanced HCC cases (50%) and in 1 of 6 early HCC cases (16.7%), as well as an increase in several other bands in tumor tissues. Conclusions: The intensity of ubiquitin staining appeared to increase in a stepwise manner from AH to advanced HCC, and the results suggest a possible correlation between changes in the ubiquitinated proteins and multistep hepatocarcinogenesis.

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.

Acute acalculous cholecystitis (AAC) usually occurs in the elderly and in those with severe pre-existing 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.

Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10 - 8 M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of 3 H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of 3 H-E3123 increased about 30-fold in acinar cells treated with cerulein (10 -8 M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supramaximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.

We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and interorgan fluxes of taurine and taurine precursors, including methionine and serine, using chronically catheterized awake dogs. In the first study, the dogs received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and arteriovenous differences during infusion and for 2 h after discontinuation of the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in 60 and 90% increases, respectively, in the arterial plasma taurine concentration. Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1 infusion. In the second study, we investigated whether Ala-Gln infusion affects taurine metabolism under normal and stress conditions. The dogs were given a constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was infused simultaneously during the second hour. Plasma concentrations and fluxes, across the liver, gut, and lung, of taurine and taurine precursors were studied. IL-1 administration increased the plasma concentration, hepatic release, and lung uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations or organ fluxes of taurine. These data suggest that cytokines play a role in taurine metabolism under stress conditions.

We report a case of renal cell carcinoma in a 49-year-old man with multiple metastases, including some to the pancreas which were initially diagnosed as primary pancreatic carcinoma. The first clinical manifestation was jaundice caused by a large metastatic lymph node. Computed tomography showed tumors in the body and tall of the pancreas as well as in the left kidney. Angiography showed that all of the lesions were hypervascular. The patient was finally diagnosed as having renal cell carcinoma. Cholecystectomy and choledochojejunostomy were performed. Intraoperative biopsy of the lymph nodes along the common hepatic artery showed spindle cell carcinoma which was compatible with renal cell carcinoma. Since renal cell carcinoma with pancreatic metastasis is rare, special attention should be paid to its differentiation from primary pancreatic carcinoma in patients with tumors in both the pancreas and kidneys.

Searching for mutations in DNA mismatch repair genes is important not only for presymptomatic diagnosis, but also for documenting the spectrum of mutations among families carrying predispositions to hereditary nonpolyposis colorectal cancer (HNPCC). We utilized an automated two-dimensional DNA typing system for mutational analysis of the hMLH1 gene and established optimal conditions for application of the technique to analysis of hMLH1. This approach enabled us to visualize 21 spots covering all 19 coding exons on a single gel and to envisage whether and where any mutations existed. All mutations that we had detected previously by other means in a panel of HNPCC patients and in one patient with sporadic endometrial cancer were also detectable by this method. Furthermore, using the 2-D system, we screened the entire coding regions of the hMLH1 gene in DNAs isolated from affected individuals belonging to two large HNPCC kindreds and four HNPCC-like kindreds, and from four patients with multiple primary cancers as well as eight sporadic colorectal cancers with replication error (RER)-positive phenotypes. We detected novel germline mutations in one HNPCC proband and one sporadic colorectal cancer with the RER-positive phenotype and one polymorphism in two HNPCC-like kindreds. This new diagnostic method is applicable to mutational analysis of any disease-causing gene, and it offers a major improvement over current approaches. Hum Mutat 9:164–171, 1997. © 1997 Wiley-Liss, Inc.

In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice. Two-dimensional gel electrophoresis and immunoblot analysis showed that only Li7NM expressed vimentin and lacked E-cadherin expression, indicating that this clone had undergone epithelial-mesenchymal transition. We then transfected mouse E-cadherin complementary DNA into Li7NM cells and found that the transfectant cells (EM16.21B.3) formed liver metastasis (8/16 mice) after intrasplenic injection and liver tumors (11/13 mice) after intrahepatic injection, whereas the control cell line formed no tumors. These results suggest that E-cadherin plays an important role in the process of intrahepatic metastasis of HCC.

BACKGROUND: Hirschsprung's disease is a congenital disorder which is rare in adulthood. In typical cases the aganglionosis involves mainly the rectum or rectosigmoid colon and the lesion starts from the anal valve. Zonal segmental aganglionosis is a very rare type even in children. PATIENT: A 54 year old women with zonal segmental aganglionosis had an aganglionic segment 18 cm in length located in the rectosigmoid colon with an 8 cm long normal appearing rectum and dilated proximal colon. Resection of the stenotic segment with end to end anastomosis was performed. CONCLUSION: The functional result was excellent five years after the operation.

Background. The significance of preserving the spleen has recently been shown. However, there are few reports of spleen-preserving distal pancreatectomy for lesions of the body and tail of the pancreas, and this procedure is not generally performed. The aim of this study was to clarify the technique and indications for spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for benign lesions of the distal pancreas. Methods. Four patients (two each with an endocrine tumor and a cystic lesion) underwent the procedure. We also performed the spleen-preserving Puestow's procedure with removal of the tail of the pancreas in a 22-year-old male patient with familial chronic pancreatitis. An important technique is to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen and to remove the splenic artery from the pancreas in the other direction. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane, which is cut longitudinally above the splenic vein. It is important to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen, because it is very difficult to remove it in the other direction. There are many branches from the splenic vein on both sides; these branches should be carefully ligated and cut. The pancreas is removed from the splenic artery from the spleen toward the head of the pancreas. This procedure is much easier than removal of the pancreas from the vein. Results. The postoperative course was uneventful in four of the five patients. A pancreatic fistula remained in one patient for several weeks. The mean and standard deviation of the operative blood loss, the duration of the operation, and the postoperative hospital stay in the four uneventful cases, excluding the one in which Puestow's procedure was performed, were 600±479 ml, 290±48 minutes, and 40±21 days, respectively. No severe complications occurred in any of the five patients. Conclusions. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein is easy and safe and should be performed for benign lesions of the distal pancreas.