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POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is a scoring system which assesses perioperative surgical risks (Copeland GP et al.: Br J Surg, 1991, Vol 78, 356-360). The POSSUM scoring system consists of two categories of assessment to assess the risk of surgery. A 12-factor (age, cardiac status, pulse rate, systolic blood pressure, respiratory status, Glasgow Coma Score, serum concentration of urea, potassium and sodium, hemoglobin concentration, white cell count and findings on electrocardiography) and 4-grade physiological score (PS) were developed. This was combined with a 6-factor (type of surgical procedure, number of procedures, blood loss, peritoneal soiling, presence of malignancy and mode of surgery) and 4-grade operative severity score (OSS). The present paper attempts to validate it retrospectively. Postoperative hospitalization period and duration of antibiotics administration were both significantly correlated with OSS, but not with PS. These results suggest that the POSSUM scoring system is useful for predicting the postoperative clinical course.

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophan-nicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cachexia.

Patients with far advanced colorectal cancers received chemotherapy consisting of low-dose cyclophosphamide (LDCY) 333 mg/m2 every four weeks intravenously and by oral administration of 5'-DFUR (a masked compound of 5-Fluorouracil). Serum levels of immunosuppressive acidic protein (IAP), an acute phase protein, were measured every four weeks for a total of thirty-one LDCY trials of ten patients. LDCY chemotherapy significantly decreased the IAP levels in cancer patients with high IAP levels. These results suggested that LDCY chemotherapy could counteract host responses against tumors and could have decreased immunosuppressive responses in cancer patients.

This study was conducted to examine the effect of gamma-interferon (IFN-gamma) on experimental metastasis formation by murine colon 26 adenocarcinoma in BALB/c mice. We found that the number of experimental lung metastases was increased after colon 26 cells were pretreated for 1 h with as little as 1 OIU/ml of IFN-gamma. 5-[125I] iodo-2'-deoxyuridine-radiolabeled colon 26 cells pretreated with IFN-gamma remained at higher level in the lung at 24h after intravenous injection than when the cells were not pretreated. In vivo elimination of asialo GM1-positive cells increased the number of lung metastases and, in such mice, there was no longer a difference in metastatic ability between control and IFN-gamma-treated cells. Colon 26 cells were completely resistant to lysis by isolated splenocytes. Splenocytes incubated in vitro with interleukin 2 exhibited moderate cytotoxicity against colon 26 cells, but there were no significant differences between control and IFN-gamma-treated cells. Colon 26 cells pretreated with IFN-gamma demonstrated resistance to tumor necrosis factor alpha-mediated growth inhibition. The enhancement of metastases by IFN-gamma was dependent on de novo protein synthesis since the enhancement was abolished by cycloheximide. Taken together, the data suggest that the metastatic ability of colon 26 cells pretreated with IFN-gamma is significantly higher due to the resistance to asialo GM1-positive cells accompanied with de novo protein synthesis.

The antitumor effects of indomethacin and interleukin 2 (IL-2) were studied in C3H/HeJ mice inoculated with MH134 hepatoma cells. Combined treatment with indomethacin and IL-2 augmented natural killer (NK) cells in mice with MH134-induced peritoneal carcinomatosis, and the survival of the treated mice was significantly longer than the non-treated mice. In animals with subcutaneous MH134 tumors, the combined therapy with indomethacin and IL-2 significantly suppressed tumor growth and induced complete regression of the tumor in three out of five mice. These results suggest that indomethacin and IL-2 therapy could be effective on human gastrointestinal cancer cells as well.

The medical records of 16 consecutive patients with Crohn's disease surgically treated in our department from 1978 to 1993 were retrospectively reviewed. The indication for surgery was obstructive symptoms due to Crohn's strictures that were unresponsive to conservative therapy. The types of operations performed were classified into five categories. Nine patients (56.3%) had small bowel resection only, 4 (25.0%) underwent an ileocolonic resection, 1 (6.3%) had a total colectomy, 1 (6.3%) had Mile's operation and 1 (6.3%) had subtotal gastrectomy with gastrojejunostomy and antral mucosectomy. Of these 16 patients, 13 (81.3%) had resection with a single anastomosis and strictureplasty was concomitantly performed in only 2 cases (12.5%). Crohn's disease recurred in 3 patients (18.8%), 1 of whom required a second operation.

PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells.

In this study, we investigated serum-soluble interleukin-2 receptor (sIL-2r) and neopterin (NPT) levels in five patients with severe postoperative infections. A total of 25 synchronous determinations of sIL-2r and NPT were performed. A marked increase in sIL-2r and NPT levels was observed, and the increase in sIL-2r was significantly correlated to that of NPT which is a marker of macrophage activity. These results suggest that macrophages are involved in the stimulation of sIL-2r release, representing a potentially negative biological effect. The results indicate that sIL-2r may be a useful indicator of the efficacy of antibiotics and of prognosis.

Familial adenomatous polyposis (FAP) is a well-known autosomal dominant disorder characterized by the formation of multiple adenomatous polyps of the colon. Gardner's syndrome is a variant of familial polyposis coli, and both can be associated with colonic or extracolonic benign and/or malignant tumors. It has been widely recognized that an adenocarcinoma of the colon develops in virtually all cases, usually at an earlier age, if polyps are left untreated. Families of four individuals diagnosed of FAP were surveyed and 56 relatives of the families were examined. Of these 56, 21 had multiple colon polyps, 3 of whom had early-stage adenocarcinomas. We consider that familial survey of FAP individuals can be of considerable benefit for this high-risk population due to the autosomal nature of the disease, allowing diagnosis of an associated cancer at an earlier stage.

Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

To improve the lymphokine-activated killer (LAK) cell therapy for liver metastasis, two methods which enhance accumulation of LAK cells in the liver were examined for their effects on the liver metastasis of Colon 26 cancer cells in BALB/c mice. Distribution of LAK cells in the mice was examined by the 51Cr labeling method. Portal vein infusion of LAK cells or tail vein infusion of neuraminidase treated-LAK (N-LAK) cells showed an augmented accumulation of infused cells in the liver. In the first experiment, LAK cells (5 x 10(7) cells) were infused in the portal vein or tail vein at days 3 and 7 after the inoculation of 5 x 10(4) tumor cells and 1 x 10(4) units of IL-2 were given three times a day from day 3 to day 7. The portal infusion of LAK cells produced a greater reduction of liver metastases compared with the peripheral infusion. In the second experiment, 5 x 10(7) LAK cells or N-LAK cells were infused via the tail vein on days 1 and 3, and 1 x 10(4) units of IL-2 were given once a day from day 1 to day 5 after the inoculation of 1 x 10(4) tumor cells. The therapeutic effect of N-LAK cells was greater than non-treated LAK cells on the number of metastatic lesions and the survival time of mice. Since access to the human portal vein is difficult and risky in clinical situation, peripheral infusion of N-LAK cells is preferable.

Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration.

Thirteen patients with rectal carcinoma seen between December 1980 and December 1990 have been reviewed to determine the risk of lymph node metastasis and its implication for subsequent treatment. The mean age was 64 years (from 38 to 79; 9 males, 4 females). The site of the tumor was predominantly in the lower rectum (53.8 percent). The polypoid (I) and flat-elevated ulcerated (IIa + IIc) subtypes were detected in seven and six lesions, respectively. Sphincter-saving techniques were carried out in eight cases, and five cases required Miles' operation. Neither postoperative complications nor deaths were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distant metastasis was found during this follow-up. IIa + IIc subtype lesions with deep submucosal invasion at or beyond Smlc level were closely related with lymphatic and vascular invasion. Although this association was not necessarily accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such IIa + IIc cases due to an increased possibility for lymph node metastasis.

In order to investigate the immunological responsiveness of tumor-bearing hosts to tumor cells, splenic suppressor cells from Ehrlich tumor-bearing mice that inhibited anti-tumor effector cell activity were characterized. In vitro cell-mediated cytoxicity and cytostasis assays were performed to test for the existence of anti-tumor immunity. suppressive activity assayed by cell mixture experiments became apparent with decline of anti-tumor immunity and progressive tumor growth. The cells mediating the suppression were found to be nylon wool column adherent T cells and inhibited T cell dependent cytotoxicity rather than non-T cell dependent cytostasis. In vivo cell transfer experiments demonstrated that intravenous injection of suppressor cells to a host already inoculated with tumor cells mixed with antitumor effector cells resulted in significant enhancement of tumor growth. This inhibition of in vivo neutralization assay be suppressor cells was found in not only allogeneic but also syngeneic tumor system. Splenectomy at the time of tumor resection endowed the host with stronger resistance against subsequent reinoculated tumor than sham-splenectomy did, reflected by prolonged survival times. These results suggest that splenectomy combined with surgical removal of the tumor is a useful treatment of clinical malignancies.