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Background: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host response. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response.Patients and Methods: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing.Results: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001).Conclusions: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer. [ABSTRACT FROM AUTHOR]

Compares the results of adrenalectomy using a retroperitoneal and a transabdominal approach, especially for adrenal carcinoma and pheochromocytoma. Intra-operative complications; Post-operative morbidity and mortality; Pre-operative localization techniques; Uni- and multivariate analysis in patients unsuitable for laparoscopic adrenalectomy.

Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis. Background. In kidney biopsies of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis, a variety of histopathological lesions occur, and their relationship to renal outcome is virtually unknown. This multicenter European study reports a clinicopathological analysis of biopsies from 157 patients with systemic vasculitis. Methods. The biopsies were evaluated according to a previously standardized scoring protocol. Serum creatinine values were measured at the time of biopsy and one year later. In addition, the lowest creatinine level during follow-up was taken into account as the optimum level of renal function recovery. The clinical prognostic value of the histopathological parameters was analyzed with the Kruskal–Wallis one-way analysis of variance and the Mann–Whitney U -test. Results. The percentage of normal glomeruli correlated most significantly with renal outcome at all points of measurement (all P < 0.001). Other lesions predicting for renal function were glomerular sclerosis (P < 0.0005 at one year after the biopsy), diffuse interstitial infiltrates (P < 0.0001 at entry, P < 0.0003 at one year), tubular necrosis (P < 0.0025 at entry), and tubular atrophy (P < 0.002 at entry, P < 0.0002 at one year). Conclusion. Traditionally, attention is focused on the extent of active lesions in the renal biopsy in order to determine the severity of renal disease and its implication for renal outcome. Because of their significant impact on renal function, combined with their easy recognition, we recommend the use of the percentage of normal glomeruli in an adequate biopsy in predicting renal function of patients with systemic vasculitis. [ABSTRACT FROM AUTHOR]

Investigates the efficacy of the continuous double-loop closure (CDLC) technique in avoiding wound complications that occur after midline laparotomy. Development of the CDLC technique to prevent wound rupture through resistance to high intra-abdominal pressure and continued approximation of wound edges; Methods; Findings; Conclusion that the CDLC technique should not be used.

Background: Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements.Methods: We did a randomised, double-blind, placebo-controlled trial in which six liver-transplant centres participated. Patients undergoing primary liver transplantation were randomly assigned intraoperative high-dose aprotinin, regular-dose aprotinin, or placebo. Primary endpoints were intraoperative blood loss and transfusion requirements. Secondary endpoints were perioperative fluid requirements, postoperative blood transfusions, complications, and mortality.Findings: 137 patients received high-dose aprotinin (n=46), regular-dose aprotinin (n=43), or placebo (n=48). Intraoperative blood loss was significantly lower in the aprotinin-treated patients, with a reduction of 60% in the high-dose group and 44% in the regular-dose group, compared with the placebo group (p=0.03). Total amount of red blood cell (homologous and autologous) transfusion requirements was 37% lower in the high-dose group and 20% lower in the regular-dose group, than in the placebo group (p=0.02). Thromboembolic events occurred in two patients in the high-dose group, none in the regular-dose group, and in two patients in the placebo group (p=0.39). Mortality at 30 days did not differ between the three groups (6.5%, 4.7%, and 8.3%; p=0.79).Interpretation: Intraoperative use of aprotinin in adult patients undergoing orthotopic liver transplantation significantly reduces blood-transfusion requirements and should be routinely used in patients without contraindications. [ABSTRACT FROM AUTHOR]

Background: Standard treatment of colorectal cancer includes adjuvant chemotherapy for patients with stage III disease (defined by the presence of lymph-node metastases), but not for patients with stage II tumors (who have no lymph-node metastases). However, 20 percent of patients with stage II tumors die of recurrent disease. We investigated whether the detection of micrometastases can be used to identify patients with stage II disease who are at high risk for recurrence. Methods: We analyzed 192 lymph nodes from 26 consecutive patients with stage II colorectal cancer, using a carcinoembryonic antigen–specific nested reverse-transcriptase polymerase chain reaction. Five-year follow-up information was obtained on all patients. Observed and adjusted survival rates were assessed in the patients with and the patients without micrometastases. Results: Micrometastases were detected in one or more lymph nodes from 14 of 26 patients (54 percent). The adjusted five-year survival rate (for which only cancer-related deaths were considered) was 50 percent in this group, whereas in the 12 patients without micrometastases, the survival rate was 91 percent (P=0.02 by the log-rank test). The observed five-year survival rates were 36 percent and 75 percent, respectively (P=0.03). The groups were similar with respect to age, sex, tumor side (location in relation to the flexura lienalis), degree of tumor differentiation (grade), and diameter of the primary tumor. Conclusions: Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer. (N Engl J Med 1998;339:223-8.) [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the first changes in cognitive and motor functioning in Huntington's disease. Forty-six gene carriers, not clinically diagnosed for HD, were compared with 88 non-gene carriers. Gene carriers performed significantly worse on the Benton Visual Retention Test. This result was due to a minority of participants who had already developed cognitive impairment. Marginal differences appeared on the motor times of single reaction time measures after correction for motor signs. The findings are discussed in the context of inconsistencies in previous studies and underscore the need for longitudinal research.

Background: WBC reduction of all blood components is being introduced in many countries. Prevention of immunologic side effects of transfusions is part of the motivation. To compare the immunogenicity of before- or after-storage WBC-reduced RBCs with RBCs without buffy coat, a randomized clinical trial was performed., Study Design and Methods: Cardiac surgery patients were randomly assigned to receive either RBCs without buffy coat (PCs), WBC-reduced RBCs that were filtered before storage (FFs), or WBC-reduced RBCs that were filtered after storage (SFs). Serum samples for antibody analyses were collected before and after surgery., Results: Sera of 404 patients were tested. Of the 317 patients with negative preoperative screening, 12.6 percent developed anti-WBC antibodies (PC, 14.5%; FF, 9.6%; SF, 13.3%). Of the 87 patients with preoperative anti-WBC antibodies, 28.7 percent showed a marked increase in panel reactivity (PC, 31.3%; FF, 29.0%; SF, 25.0%). ELISA showed the newly formed antibodies to be of IgG class and directed against HLA class I in more than 90 percent of the samples tested. Newly formed anti-RBC antibodies appeared in 5.3 percent (PC, 7.1%; FF, 3.4%; SF 5.4%). Alloimmunization against WBCs and RBCs was strongly correlated (p < 0.01). The differences in newly formed anti-WBC antibodies and anti-RBC antibodies between the trial arms did not show significance., Conclusion: Buffy coat removal, and additional WBC reduction by filtration, either before or after storage, result in similar posttransfusion alloimmunization frequencies after a single transfusion event with multiple RBCs.

A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistent thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0.005) and an unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.

Objective: To identify markers that are relevant as predictors of lymph node metastasis in head and neck squamous cell cancer., Design: Expression of p53, Rb, cyclin D1, E-cadherin, and epithelial cell adhesion molecule was examined using immunohistochemical analysis and traditional histological parameters, and the correlation of these markers with the histologically verified presence of regional metastases was determined., Subjects: The study sample comprised 121 patients with head and neck squamous cell cancer from whom paraffin-embedded material of primary tumors was used., Results: Lymph node metastasis was correlated with the loss of expression of Rb (P =.04) and marginally correlated with the loss of expression of E-cadherin (P =.06). If the results are broken down to subsites, loss of E-cadherin expression in oral cancer (P =.04) and absence of eosinophilic infiltration in laryngeal cancer (P =.003) correlated with nodal metastasis. None of the other markers correlated. A combination of relevant parameters did not result in a much stronger correlation., Conclusions: The expression of the investigated genetic markers and histopathological features of primary tumors can supply limited information on the metastatic behavior of tumors. Although the use of markers for regional metastasis would be a welcome additional tool, these results do not warrant the use of these parameters for clinical decision making concerning the treatment of the neck in patients with head and neck squamous cell cancer.

Objective: To decide whether partial nail extraction with phenolisation or with partial excision of the matrix should be the standard treatment in patients with ingrowing toenails of the hallux., Design: Randomized clinical trial with 12-month follow-up evaluations performed by observers who did not know which procedure was applied., Setting: Outpatient department of a surgical teaching hospital., Patients: Fifty-eight consecutive patients with a total of 63 ingrowing toenails were randomized., Intervention: Thirty-four partial matrix excisions ("matrix" group) and 29 phenolizations ("phenol" group) were performed., Main Outcome Measures: Recurrence rate, postoperative morbidity (pain, wound exudates, and scar discomfort), and time to complete recovery (wearing shoes, performing normal activities/work)., Results: Recurrences were seen after 7 procedures in the matrix group and also after 7 procedures in the phenol group, of which patients were symptomatic and required a second operation in 4 and 3 instances, respectively. None of the observed differences in wound healing, postoperative pain, and recovery were statistically significant., Conclusions: Partial matrix excision and phenolization are equally effective in treating ingrowing toenails. Because the use of the toxic agent phenol should be avoided, partial matrix excision is the preferable procedure. But in view of the high recurrence rate, there is a need for further improvement of the treatment of ingrowing toenails.

There appears to be a relationship between mitotic activity and malignant behavior in adrenocortical tumors, and carcinomas with a high mitotic index may have a poorer prognosis. This has been investigated further by quantifying and comparing the Ki-67 index using antibody MIB-1 in a series of 14 adrenocortical adenomas and 40 carcinomas. The levels have been correlated with survival and disease-free survival in carcinomas and with evidence of abnormal p53 expression as detected by immunohistochemistry. Nevertheless, many carcinomas have a low level of proliferation that may reflect varying abnormalities within the regulation of both cell division and apoptosis. Expression of bcl-2 protein, an inhibitor of apoptosis has therefore also been examined. The Ki-67 index in carcinomas was significantly higher than in adenomas, but below 4% there was overlap. There was no significant difference in survival between carcinomas with MIB-1 index <3% and those greater, but the lower group had significantly longer disease-free survival (p = 0.02). There was no significant difference between p53 immunopositive and p53 immunonegative carcinomas. No tumor showed immunopositivity for bcl-2 protein. It is concluded that MIB-1 index may contribute additional prognostic information in adrenocortical tumors. Inhibition of apoptosis by bcl-2 does not appear to play a role in tumor growth.