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Background. Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases (MMPs) that are considered to contribute to cancer invasion and metastasis. One of the gene products that the authors have isolated by a cDNA subtraction of human gastric cancer minus normal gastric mucosa is MMP-7. The purpose of this study was to examine the expression of MMP-7 mRNA in different stages of human colorectal carcinomas. Methods. A subtracted complementary DNA library was generated from a paired sample of human gastric carcinoma minus normal gastric mucosa. Screening of the library clones determined that MMP-7 mRNA was overexpressed. The complementary DNA insert was then used as a probe to evaluate the expression in a larger number of surgical samples of human colorectal carcinomas by Northern hybridization. Results. The mRNA signal was greater in the colorectal carcinoma than in paired adjacent normal colonic or rectal mucosa in 39 of 47 cases. The expression of MMP-7 mRNA in tumor tissues increased with increasing Dukes' stage (P < 0.05). The MMP-7 mRNA expression was greatest in the metastatic liver lesions. Conclusions. The findings imply that MMP-7 mRNA is overexpressed in human colorectal carcinomas and that MMP-7 may prove useful as a marker of biologic aggressiveness. Cancer 1995;75:1516-9.

Background. Recent studies have shown that microsatellites are unstable in various types of cancers, and such genetic instability at the microsatellite loci (microsatellite instability) has been considered to play an important role in the development of cancer. However, the clinicopathologic significance of microsatellite instability in gastric cancer has not been clarified. Methods. To elucidate the role of genetic instability in the development of gastric cancer, the presence of microsatellite instability was examined in 25 cases of gastric cancer using fresh-frozen tumor-normal paired samples using a polymerase chain reaction (PCR)-based method. Microsatellite instability was defined as tumors that showed altered banding patterns at two or more microsatellite loci. Results. The incidence of microsatellite instability in gastric cancer cases was 4 of 25 patients (16%) and 4 of 26 cancers (15%). A significantly high incidence of microsatellite instability was observed in both the elderly (P < 0.01) and in lymph node metastasis-negative patients (P

Background. N-acetylation polymorphism has been documented as a representative pharmacogenetic trait, and also has been implicated ecogenetically in an individual's susceptibility to cancer. However, there still remains controversy concerning the association between colorectal cancer and N-acetylation polymorphism. Methods. A newly established molecular genotyping method using polymerase chain reaction-based restriction fragment length polymorphism to analyze the distribution of polymorphism in a large group of japanese patients with colorectal cancer was used. Results. Based on an analysis of 234 Japanese patients with colorectal cancer and 329 healthy control subjects, no significant difference was observed in either the distribution of acetylator phenotypes or of allele frequencies between the two groups. In addition, no significant difference in their distribution was found based on the age at which cancer was first detected, the location of tumors, or the histopathologic features. Conclusions. N-acetylation polymorphism does not appear to be implicated crucially as a genetic trait affecting an individual's susceptibility to colorectal cancer.

We developed a reliable procedure for obtaining sufficient blood flow at the anastomotic site of the gastric tube for esophageal reconstruction. By utilizing the junction between the left gastroepiploic and short gastric vessels via the splenic hilar vascular arcade, the distal portion of the gastric tube could be sufficiently nourished. The application of this technique resulted in a complete prevention of postoperative anastomotic leakage after antesternal esophageal reconstruction.

Accurate detection of breast tumors and discrimination of tumor from normal tissues during breast-conserving surgery are essential to reduce the risk of misdiagnosis or recurrence. However, existing probes show substantial background signals in normal breast tissues. In this study, we focus on glycosidase activities in breast tumors. We synthesized a series of 12 fluorescent probes and performed imaging-based evaluation on surgically resected human breast specimens. Among them, the α-mannosidase-reactive fluorescent probe HMRef-αMan detected breast cancer with 90% sensitivity and 100% specificity. We identified α-mannosidase 2C1 as the target enzyme and confirmed its overexpression in various breast tumors. We found that fibroadenoma, the most common benign breast lesion in young woman, tends to have higher α-mannosidase 2C1 activity than malignant cancer. Combined application of green-emitting HMRef-αMan and a red-emitting γ-glutamyltranspeptidase probe enabled efficient dual-color, dual-target optical discrimination of malignant and benign tumors.

The chronologic changes in the serum levels of interleukin-6 (IL-6), a mediator for acute-phase inflammation, were compared between laparoscopic cholecystectomy (LC) and open cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. The increase in the serum IL-6 level during LC was found to be significantly smaller than that during OC and resulted in a smaller extent of postoperative elevations for C-reactive protein. These results suggest that laparoscopic surgery associated with minimal tissue injury can help limit an increase in the serum IL-6 level during surgery, thus contributing to a reduction in surgical stress.

Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins and play indispensable roles in various physiological and pathological processes. However, only a few highly activatable fluorescence probes for CPs have been reported, and there is a need for a flexibly tunable molecular design platform to afford a range of fluorescence probes for CPs for biological and medical research. Here, we focused on the unique activation mechanism of ProTide-based prodrugs and established a modular design platform for CP-targeting florescence probes based on ProTide chemistry. In this design, probe properties such as fluorescence emission wavelength, reactivity/stability, and target CP can be readily tuned and optimized by changing the four probe modules: the fluorophore, the substituent on the phosphorus atom, the linker amino acid at the P1 position, and the substrate amino acid at the P1′ position. In particular, switching the linker amino acid at position P1 enabled us to precisely optimize the reactivity for target CPs. As a proof-of-concept, we constructed probes for carboxypeptidase M (CPM) and prostate-specific membrane antigen (also known as glutamate carboxypeptidase II). The developed probes were applicable for the imaging of CP activities in live cells and in clinical specimens from patients. This design strategy should be useful in studying CP-related biological and pathological phenomena.

Patients with collagen diseases have been reported to demonstrate a greater risk when undergoing surgical operations. To determine the risk factors in abdominal surgery for patients with collagen diseases, 32 patients with collagen diseases who underwent abdominal surgery were analyzed for their clinical features and surgical results by comparing 26 cases from the favorable prognosis group (Group A) and 6 cases resulting in hospital death (Group B). The analysis revealed that emergent operations tended to result in worse outcomes (P= 0.011) than elective operations and that cases undergoing operations for collagen disease-related problems, including intestinal perforation and acute pancreatitis, also showed a worse postoperative course than those who underwent operations for problems unrelated to collagen diseases, such as carcinomas and cholelithiasis (P= 0.0006). The dose of steroids administered at the time of operation was also significantly higher in Group B than in Group A (P= 0.03). These results suggested that the patients with collagen diseases should be followed periodically not only for the primary disease but also for any potential surgical diseases to identify such diseases at an early stage and to avoid an emergent operation, and that patients treated with high doses of steroids also need intensive care after abdominal surgery.

Because of the rarity of apocrine carcinoma and lack of standardized criteria for the diagnosis, the definitive conclusions of clinicopathologic features and the prognosis has not been determined. We retrospectively examined data on 2091 curatively treated Japanese patients with primary breast carcinoma. Among them, 33 (1.6%) who had been diagnosed of apocrine carcinoma were reviewed. Compared with non-apocrine carcinoma, apocrine carcinoma was characterized by less positive rates of ER and PR, and by frequent rates of unilateral multicentric breast carcinoma with significant difference. The clinicopathological factors influencing 12-year survival rate were lymph node metastasis, lymphatic involvement and vascular involvement. There was no difference in survival rates at 10 years after operation between apocrine carcinoma and non-apocrine carcinoma. Our result shows unique hormone response and unilateral multicentricity are only typical clinicopathological features of apocrine carcinoma.

Human esophageal carcinomas occur more frequently in males, suggesting that androgens may play a role in the regulation of gene expression associated with malignant transformation. We previously established an androgen-sensitive squamous cell carcinoma line, KSE-1, from a male patient with esophageal cancer; recently a novel isoform of human fibroblast growth factor 8 (FGF8f, isoform FGF8b) was identified and expressed following androgen stimulation of KSE-1 cells. The predicted amino acid sequence of FGF8f contained an additional 29 amino acids when compared to FGF8b. Flutamide, an androgen antagonist, inhibited both FGF8b and FGF8f transcription in a dose-dependent manner. Tissue analysis from tumors revealed FGF8b expression in 24 of 41 male, but in 0 of 9 female esophageal carcinomas (58.5%), and none in adjacent normal esophageal mucosa. In addition, FGF8f was detected in 9 of 24 FGF8b-positive tumors (37.5%), and this observation was significantly associated with a poor prognosis (P < 0.001).Our observations suggest that androgenic exposure will induce FGF isoforms in tumor cells, and expression of these growth factors is associated with the prevalence and prognosis of esophageal carcinoma in males.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. However, TIMP-1 possesses another important function, cell growth promotion. The clinical significance of TIMP-1 expression has not been fully determined in esophageal carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor (T) and corresponding normal (N) tissues of 85 esophageal carcinoma cases by RT-PCR. The T:N ratio of TIMP-1 mRNA expression in each case was evaluated semi-quantitatively with adjustment by an internal control gene. The mean T:N ratio was 2.0 (range 0.2–6.5). When comparing high-expression cases (T:N > 2.0, n = 37) with low-expression cases (T:N ≤ 2.0, n = 48), the former showed a significantly higher frequency of lymph vessel invasion, vascular vessel invasion, lymph node metastasis and advanced-stage disease. The former cases showed a poorer prognosis than the latter. Multivariate analysis disclosed that TIMP-1 expression status was an independent determining factor for prognosis. Our findings suggest that TIMP-1 expression correlates with tumor extension of esophageal carcinoma and might, if validated, prove useful as a novel prognostic marker for esophageal carcinoma. Int. J. Cancer 88:575–578, 2000. © 2000 Wiley-Liss, Inc.

L‐myc polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there have been no reports concerning the association between esophageal cancer and L‐myc polymorphism. To analyze the distribution of polymorphism in Japanese patients with esophageal cancer, a molecular genotyping method using a polymerase chain reaction‐based restriction fragment length polymorphism (PCR‐RFLP) was used. Based on an analysis of 65 Japanese patients with esophageal cancer and 107 healthy control subjects, a significant difference was observed in either the distribution of genotypes (P=0.012) or of allele frequencies between the two groups (P0.004). The relative risk of esophageal cancer for genotypes including the shorter allele was 2.9 compared to the longer allele homozygote. Furthermore, the patients with S‐allele had a tendency for poor prognosis among those with three genotypes. A significant difference between the distribution of genotypes and the incidence of lymph node metastasis was found based on the clinicopathological features of the cancers. These results suggest that L‐myc polymorphism may be implicated as a genetic trait affecting an individual's susceptibility to esophageal cancer, at least among Japanese patients.

Abstract: The induction of cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using MAGE peptide has been investigated in order to use MAGE antigens immunotherapeutically. We therefore developed a simplified method for inducing peptide-specific CTL that kill tumor cells expressing MAGE from the PBMC of either healthy donors or even cancer patients. Since the spleen is a major lymphoid organ, we used a simple method to examine the capacity of spleen cells to generate MAGE-specific CTL by in vitro stimulation with MAGE peptide in gastric cancer patients. The CTL responses could thus be induced from unseparated spleen cells in HLA-A2 patients with gastric carcinoma expressing MAGE-3 by stimulating these cells with autologous spleen cells pulsed with HLA-A2-restricted MAGE-3 peptide as antigen-presenting cells and by using keyhole limpet hemocyanin and interleukin-7 for the primary culture. The induced CTL were thus able to lyse HLA-A2-positive carcinoma cells transfected with MAGE-3 and expressing MAGE-3, as well as the target cells pulsed with the peptide, in an HLA-class-I or -A2-restricted manner. Since MAGE-specific CTL could be induced from the spleen cells of gastric cancer patients, the spleen appears to play an important role in either clinical tumor vaccination or the treatment of cancer patients by adoptive immunotherapeutic approaches using the MAGE peptide.

We report here the outcome of surgical treatment for gastric cancer in 54 patients over 80 years of age presenting from 1967 to 1989. The mean observation interval of the postoperative period was 24 days. In most cases, preoperative examinations revealed pulmonary, renal or cardiac disturbances. The postoperative morbidity rate was 40.7%, most commonly as a result of pulmonary complications. In the 2 patients with multiple organ disturbances, 1 died 1 day after operation following myocardial infarction and the other died of pneumonia 12 days postoperatively. Intensive care treatments were needed in the early postoperative period. The increased morbidity rate proved to be related to wide resectional procedures such as total gastrectomy, operative time in excess of 3 hours, and intraoperative blood loss >300 ml (p<0.05). When adjustment for confounding variables was made in the multivariate discriminant analysis, the type of surgery proved to be a major independent risk factor related to postoperative complications. The majority of tumors (92.6%) could be removed by standard resectional procedures and curative operation was feasible for 36 (66.7%) patients. There were 24 deaths due to progression of the cancer. The crude overall 5-year actuarial survival rate was 23.8%, while the rate was 36.9% when correction was made for sex and age. The probability of long-term survival for patients in a relatively early stage of disease (T1-2, N0-1) was statistically better than for those with a more advanced disease (T3-4, N2, M1). Thus, even for patients in the 8th decade of life, gastric surgery can be considered, for carefully selected patients.

Gastric cancer concomitant with pregnancy is rare. In order to determine the clinical problems and practical guidelines on this particular subject, 61 Japanese patients were analyzed for clinical features and the results of obstetric and surgical treatment corresponding to the time of detection of the gastric cancer during the gestational period. The data indicated a limitation in diagnostic approaches caused by pregnancy and difficulty in saving both the mother and the fetus. Only 20 (58.8%) of the pregnant women underwent both obstetric treatment for the fetus and surgical treatment for gastric cancer. Fifty-nine of the gastric cancer cases (96.7%) were advanced and resectability was consistently low (47.5%). The patients who received gastrectomy had a high incidence of hospital death (22.7%) and a poor prognosis—21.1% 3-year survival. Based on the authors' cases of both early and advanced gastric cancer associated with pregnancy, the importance of early detection by gastroendoscopy is emphasized.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a presumed activator of MMP2, which is one of the major proteinases in tumor cell invasion. In this study, we determined the clinico-pathologic significance of MT1-MMP expression in 68 human gastric carcinomas. The tumor-normal ratio (T/N ratio) of MT1-MMP expression was determined by reverse transcription-polymerase chain reaction analysis. To visualize the localization of MT1-MMP, an immunohistochemical study was performed. In addition, a gelatin zymography was done to examine the activation ratio of MMP2, and a correlation between MT1-MMP expression and activation of MMP2 was studied. The expression of MT1-MMP mRNA was higher in tumor tissue than in corresponding normal tissue in most cases. The mean value of the T/N ratio was 4.8. Twenty cases with T/N ≥ 4.8 showed significantly deeper invasion and higher frequency of lymph node metastasis than 48 cases with T/N &lt; 4.8. MT1-MMP expression was an independent factor influencing both tumor invasion of the gastric wall and lymph node metastasis. Although MT1-MMP expression was not an independent prognostic factor, the patients with T/N ≥ 4.8 showed a significantly worse prognosis than those with T/N &lt; 4.8. An immunohistochemical study demonstrated that MT1-MMP expression was mainly recognized in the tumor cells. There was a significant correlation between MT1-MMP expression and activation of MMP2. Our findings suggest that: 1) the expression of MT1-MMP may influence prognosis via tumor invasion of the gastric wall and lymph node metastasis, and 2) MT1-MMP activation of MMP2 may be clinically relevant in gastric carcinoma tumors. Int. J. Cancer 74:316-321, 1997. © 1997 Wiley-Liss, Inc.

Neuroleptic malignant syndrome (NMS) is a potentially fatal complication which may develop in psychiatric patients taking neuroleptic drugs. We report herein the successful treatment of a 33-year-old schizophrenic man, prescribed neuroleptic drugs, who underwent an emergency operation for traumatic duodenal perforation with a retroperitoneal infection. Five days after the operation, he began to demonstrate clinical features consistent with NMS such as high fever, abnormalities in vital signs, leukocytosis, and an elevated serum level of creatine phosphokinase; however, these findings were first presumed to be secondary to either the preexisting tissue injuries or to postoperative complications. A definite diagnosis of NMS was thus delayed until muscle rigidity and autonomic instability became evident. After a tentative diagnosis of NMS had been made, sodium dantrolene, a drug used specifically for the treatment of NMS, was administered and the patient's condition remarkably improved. Since NMS can be induced by either interrupting the course of neuroleptic drugs or by the additional administration of sedative drugs, and since its mortality rate is high if prompt and appropriate treatment is not carried out, surgeons should bear in mind the possibility of NMS developing postoperatively in psychiatric patients.

We previously found that the ability of peripheral blood mononuclear cells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administration. On the basis of the clinical finding, we designed a treatment regimen comprised of 12 mg/m2 mitomycin C i. v. on day 1 and 700 U/m2 recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural killer activity, lymphokine-activated killer (LAK) activity, and the ability to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this therapy. The relationship between these parameters and the clinical antitumor response to this treatment was examined. Although the cytotoxic activities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the changes in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose disease remission was partial or minor were defined as responders. Further, phenotypic analysis showed a significant increase in CD2+, CD3+ CD4+ and CD4+Leu8- cells after the firs course, and CD25+ cells after either the first or second course of this treatment. The precentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets was related to clinical response.

Summary On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.

Summary The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P <0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P <0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P <0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m2, i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. Pretreatment values of total white blood cell and lymphocyte counts, and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-I-β was increased after the treatment in both responders and nonresponders, whereas IL-1-α production was not increased. In addition, a significant increase in the ability to produce TNF-α was observed only in responders, indicating the correlation of TNF-α production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment.

PURPOSE: Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis. An elevated protein level of ODC was observed in the tumors. There has been, however, little information reported so far on the expression of ODC messenger ribonucleic acid (mRNA) in clinical colorectal carcinomas.In vitrostudies disclosed that the transcriptions of the ODC gene is regulated by the c-mycgene. METHODS: The expression of ODC and c-mycmRNA in biopsy specimens obtained from both tumor tissue and the corresponding normal tissue was examined by the reverse transcriptase polymerase chain reaction method in 40 cases of colorectal carcinoma. RESULTS: The expression of ODC mRNA was observed in both tumor tissue and normal tissue. The tumor to normal ratio of ODC mRNA was higher in cases with deeply invasive tumors than in cases with shallow tumors, and it was also higher in Dukes B or C cases than in Dukes A cases. There was a significant correlation between the tumor to normal ratio of c-mycmRNA and that of ODC mRNA in each case. CONCLUSIONS: These findings suggested that 1) the study of the expression of ODC mRNA may be useful for preoperatively predicting more advanced disease of colon carcinoma, and 2) there was a significant correlation between expression of ODC and c-mycmRNA in the clinical samples, which was similar to the findings of a previousin vitrostudy.

The clinical evaluation of esophageal reconstruction in both resectable and unresectable carcinoma of the thoracic esophagus is described. Our operative technique for obtaining a long gastric tube and creating an end-to-side anastomosis has been highly successful, and the anastomotic failure rate was remarkably lowered in patients with resectable carcinoma of the esophagus. However, anastomotic leakage remains a serious problem for those undergoing esophageal bypass for unresectable carcinoma of the esophagus. The most likely cause of anastomotic failure after bypass seems to be the tug on the anastomosis with each swallow.

Abstract: Eighteen cases of mesenteric panniculitis of the colon collected from the literature, together with two cases from the authors' source, were reviewed. The disease occurred most often in late adult life, with a male predominance. Symptoms were abdominal pain, diarrhea, constipation, and a lower abdominal mass in most patients. Barium enema disclosed narrowing, shortening, and poor extensibility of the colon, and ultrasonography and computed tomography showed thickening of the mesocolon and colonic wall with soft-tissue density. Exploratory laparotomy was done in all patients, and colectomy, colostomy, or other surgical treatments were performed in 17 (85 percent). Gross appearance at the time of surgery was characterized by a marked thickening or a firm mass of the mesocolon with a puckered surface involving the appendices epiploicae of the colon. Microscopically, degeneration of the adipose tissue, revealed by aggregates of lipid-laden macrophages, was diagnostic. Inflammatory infiltration and fibrosis also were present in many patients. Mesenteric panniculitis of the colon seems to be a lesion more advaced than the same condition of the small intestine, and colostomy or bypass surgery may be needed for alleviation of severe symptoms.

Abstract: Left suprarenal-inferior mesenteric venous shunt (Inokuchi) was prescribed for 80 patients with recurrent breast cancer and the efficacy of hormone coditioned cancer chemotherapy was assessed. The patients were separated into 3 groups according to the historical regimen of combined chemotherapy: Group I; surgical hormone therapy alone, Group II; surgery plus short term chemotherapy, and Group III; surgery plus long term chemotherapy. The 5 year survival rate of the responsive patients to the surgical hormone therapy was as high as 84.6 per cent in Group III, as compared to that of Groups I and II, 41.7 per cent and 16.7, respectively. Survival was not prolonged in non-responsive patients, regardless of the group. These findings indicate that surgical hormone therapy combined with postoperative long term cancer chemotherapy is a valid and effective method for treating recurrence of breast cancer.

Summary: Primary cultures of 9-d-gestation Syrian hamster embryo (E9) cells are distinct from primary cultures of later gestational age in terms of their growth and differentiation. First, primary E9 cell cultures express multiple mesenchymal differentiation lineages (e.g., adipocyte, myoblast) only rarely seen in cultures of 13-d-gestation fetal (F13) cells. Second, although most primary E9 cultures have a limited in vitro proliferative life span and exhibit cellular senescence similar to primary cultures of F13 cells, E9 cultures seem to have higher frequency of escape from senescence and conversion to continuous cell lines compared to F13 cells. Moreover, this frequency can be further increased 4- to 5-fold by continuous exposure of the E9 cells to tumor promoters or epidermal growth factor. Eleven continuous cell lines have been isolated from unreated, promoter-treated, or epidermal growth factor-treated primary E9 cultures. Seven of these are neoplastic or preneoplastic. However, the remaining four do not show any evidence of being in neoplastic progression and three of these continue to express the same differentiated phenotype observed in ther parental primary cell cultures.

A comparative study of two different species ofafluorouracil assay was conducted on 11 patients who had carcinoma that was deemed unresectable after the surgical operation. For these patients FU at a dose of 10 mg/kg was intravenously administered before operation, and portions of the tumors were resected within 120-150 min to assay both the (FU)RNA/RNA and FU/protein. After surgery, all patients were given FU alone either intravenously or orally. The FU, which was in an acid-soluble material (FU/protein), was not related to the antitumor effect ofFU. However, the FU in RNA f(FU)RNA/RNA)] was found to be related to the antitumor effect ofFU. When the concentration of (FU)RNAZRNA was above approximately 200 ng/mg, FU was effectual in unresectable carcinomas. It is probable that the (FU)RNAZRNA may be more suitable than FU/protein for predicting the antitumor effect of FU.

Abstract:  After activation with interleukin-2 (IL-2), peripheral blood mononuclear cells (PBMC) have been reported to induce the expression of mRNA coding various cytokines, including interleukin(IL)-1α, -1β and tumor necrosis factor α (TNFα). We examined the cytokine mRNA expression of PBMC following treatment with IL-2 in vitro and in vivo by a quantitative method using the reverse transcription/polymerase chain reaction (RT-PCR). After stimulating PBMC with IL-2 in vitro, peak levels of IL-1α mRNA were reached between 3 h and 12 h, and thereafter declined. The IL-1β expression increased, with levels peaking at 1–6 h and, had decreased by 96 h. The expression of TNFα was elevated both 1–3 h and 24–48 h after stimulation. The peak levels of IL-1α and -1β mRNA and the early elevation of TNFα mRNA mainly accounted for the cytokine mRNA expression in adherent cells; however, the late induction of TNFα mRNA was observed in nonadherent cells. In patients with advanced carcinoma, the IL-1α and -1β mRNA expression were elevated after IL-2 treatment for 5 consecutive days, while the expression of TNFα mRNA also increased. These results indicate that the quantitative RT-PCR method appears to be useful for analyzing the cytokine mRNA expression of PBMC after treatment with IL-2.

A case of α-fetoprotein (AFP)-producing gastric cancer, which showed a huge abdominal mass due to an exogastric growth, is here described. A 69-year-old Japanese woman with a huge abdominal mass, measuring 22 × 15 cm in size, had a serum AFP level that was exceptionally high (155 × 103ng/ml). CT, barium meal studies, and gastrointestinal fiberoscopy revealed a gastric tumor with an exogastric growth pattern. The patient underwent a partial gastrectomy. The histological examination revealed that the tumor consisted of anaplastic carcinoma with positive staining for AFP. Although no liver metastasis was observed at operation, she died of multiple liver metastases 8 weeks after the operation. A gastric cancer that shows both AFP production and an exogastric growth pattern is quite rare and may be virulent.

Abstract: A 55 year old man with a short history of continuous vomiting and recent episodes of midabdominal pain and high fever was discovered to have a complete duodenal obstruction caused by acute appendicitis and intestinal malrotation. A fibrous adhesion caused by the inflamed appendix in the high caecum involved the duodeno-jejunal junction. This case is unique in that the onset of acute appendicitis triggered duodenal obstruction in the presence of an asymptomatic malrotation.

Abstract: We recently discovered that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C (MMC) administration. Based on our clinical findings, we designed a treatment regimen comprised of MMC 12 mg/m2 given intravenously on day 1 and recombinant interleukin 2 (rIL 2) 700 U/m2 given intravenously every 12 hr from day 4 through day 8, when the generation of LAK cells had been shown to be markedly increased. Ten patients with various advanced carcinomas for which standard therapy had failed or no standard therapy was available, were treated with this regimen. Of these ten, three had a partial response and three others had a minor response. Fevers were common and anemia occurred in four patients, but nevertheless, severe toxicity was not encountered. These results indicated that rIL 2 in combination with MMC might be effective against advanced carcinoma without causing severe toxicity when these drugs are used in an appropriate combination.

Abstract: Since the late 1970's, there has been a remarkable decrease in the mortality of patients with esophageal cancer. Factors such as progress in pre- and post-operative management, operative technique, and anesthesia all play a contributory role in this improvement. Among 251 Japanese patients with esophageal carcinoma who underwent esophageal resection and reconstruction in our department of surgery since 1965, those treated from 1965–74 and others treated from 1975–1984 were investigated in detail. It became clear that pulmonary complications and anastomotic leakage were the two major complications related to operative mortality. The former has decreased by intensive postoperative care with strong emphasis on cough dynamics, and the latter because of the long gastric tube we devised and which has a good blood supply. These positive events make feasible early postoperative irradiation and cancer chemotherapy.

Abstract: We treated a 66-year old woman with mucoepidermoid carcinoma of the esophagus. The histologic features of this tumor seemed to originate from esophageal glands and their ducts. This deduction was based on the subepithelial growth pattern and the presence of in-situ carcinoma showing a glandular or squamous pattern at the location of the esophageal gland duct. Although the biological nature of this tumor was not elucidated, the prognosis is similar to that seen with the ordinary type of esophageal squamous carcinoma.

Abstract: As complete dissection of metastatic lymph nodes in the upper mediastinum is impossible in conventional surgery for esophageal carcinoma, we devised a form of intraoperative local adjuvant cancer chemotherapy for metastatic lymph nodes of the mediastinum,via tracheal bifurcation lymph nodes located at the anatomical pivot in the upper mediastinal lymph flow. Emulsion type bleomycin (BLM) was injected into the bifurcation lymph nodes of mongrel dogs, and BLM was identified in the pulmotracheal lymph nodes within 20 minutes. When the cervicothoracic lymph nodes in the ipsilateral side were dissected beforehand, the BLM levels in the contralateral side doubled those seen in the controls. In rabbits with VX2 carcinoma, the level of BLM decreased in lymph nodes with metastasis, however, the spread was still evident even when about 75 per cent of the nodes were occupied with metastasis.