Immunohistochemical assessment of basement membrane components in colorectal cancer: prognostic implications.

Loss of basement membrane integrity during neoplastic invasion may have some direct prognostic significance, which is worth investigating. We studied 151 cases of colorectal adenocarcinomas retrospectively. The aim of the study was to investigate the immunohistochemical expression as well as the distribution of laminin and collagen IV within the basement membranes of cancer cell formations. The results were related to histological grade of malignancy (I, II or III) and Dukes' staging of all tumours as well as to 3-year survival status in 52 patients. Using the immunostaining method of strept ABComplex/HRP and appropriate monoclonal or polyclonal antibodies, we assessed the continuity, the discontinuity of the distribution or the total loss of structural basement membrane components alongside the infiltrating borders of each tumour. The results were evaluated statistically. Either a considerable degree of discontinuity or a total loss of basement membrane components was more common in moderately and poorly differentiated adenocarcinomas (p = 0.002 and p = 0.005 for collagen IV and laminin, respectively) and they seemed to be adversely associated with survival status (p = 0.066 and p = 0.014 for collagen IV and laminin, respectively). Interestingly, no association with the stage of disease was noticed. The results of this study reinforce the value of laminin and collagen IV as possible prognostic factors independently to tumour stage. The total loss or considerable discontinuity of the basement membranes of cancerous cells can be considered as indicators of tumour aggressiveness.

Laparoscopic management of large retroperitoneal lymphoceles complicating aortic surgery.

Retroperitoneal lymphocele is a rare but debilitating complication of aortic replacement with synthetic graft. The only effective treatment reported to date is surgical reexploration and ligation of leaking lymphatics. This report illustrates the successful management of two patients with large retroperitoneal lymphoceles formed after aortic surgery using laparoscopic techniques. The available literature is reviewed. Laparoscopic fenestration of the lymphocele and laparoscopically assisted ligation of the leaking lymphatics combined with internal drainage resulted in long-term relief of compression symptoms, as observed, respectively, over the 5-year and 3-month follow-up periods. Percutaneous catheter drainage before laparoscopic management was unsuccessful in both cases. In addition, the unique presentation of a large retroperitoneal lymphocele with intestinal obstruction is reported, and currently available treatment options are discussed.

Sweat gland carcinoma with multiple local recurrences: a case report.

We report a case of primary, high grade sweat gland carcinoma, a rare tumor, occurring in the skin of the left axilla. The patient, a 54-year-old man, was treated with wide surgical excision and lymph node dissection; he had developed metastatic deposits in one regional lymph node. The neoplasm relapsed locally thrice in a period of 10 years; however, distant metastases were not found. The differential diagnosis of sweat gland tumors is discussed in the present article.

The use of TWH catheters in CAPD patients: fourteen-year experience in technique, survival, and complication rates.

OBJECTIVE: To evaluate the technique of insertion, complication rates, and survival rates of Toronto-Western Hospital (TWH) peritoneal catheters in continuous ambulatory peritoneal dialysis (CAPD) patients. PATIENTS AND METHODS: A total of 222 TWH catheters were inserted into 203 CAPD patients (113 males and 90 females) with end-stage chronic renal failure during a period of 14 years (1 January 1982 to 31 August 1995). The mean age of the patients was 58.5 years (range 18-86 years). For the first 6 years, the peritoneal cavity approach was performed via a lower midline incision (45 insertions), various other approaches (17 insertions), and, finally, for the last 160 insertions (for approximately 8 years) the transverse paraumbilical incision was exclusively employed. The duration of CAPD ranged between 1 to 151 months (mean time 33.2 months). RESULTS: Regarding early and late complications (namely leakages, obstructions, eviscerations, tunnel infections, herniation, and others), as well as catheter survival, the transverse paraumbilical insertion, compared to other approaches, had the smallest number of complications. Thus, early leakage occurred in 5/222 (2.25%) versus 10/222 (4.5%), obstruction nil versus 2/222 (0.9%), and evisceration nil versus 1/222 (0.45%). In addition, as far as the late complications are concerned: tunnel infections 5/222 (2.22%) versus 13/222 (5.85%), herniations 1/222 (0.45%) versus 16/222 (7.3%), and cuff protrusion nil versus 7/222 (3.1%). Finally, overall peritonitis occurred with a rate of one episode every 21.2 months. Actuarial survival for 1 and 3 years was 75% and 37%, respectively. CONCLUSIONS: The transverse paraumbilical incision seems to be the most advantageous approach in inserting (by "surgical method") theTWH catheters. We found it to be a safe, simple, versatile procedure, giving good results in all parameters concerned.

Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Cathepsin D (CD), an estrogen-regulated lysosomal protease, has been detected in a variety of tissues. CD expression has been correlated with the invasive potential of breast cancer, acting as an autocrine mitogen or as a protease that degrades the extracellular matrix. The role of CD expression in predicting prognosis or invasive potential in colorectal carcinomas is mostly unknown. METHODS: CD immunohistochemical expression was studied in 60 surgical specimens of colon adenocarcinomas. A three-step avidin biotinylated, horseradish immuno-peroxidase (ABC-HRP) staining technique was performed on 4 microm paraffin-embedded tissue sections with a polyclonal antibody to CD. RESULTS: Carcinoma cells showed positive CD immunostaining in 41.6% of adenocarcinomas (50%, 43.7%, 37.5%, and 25% of Dukes' Stage A, B, C, and D, respectively). Nonneoplastic stromal cells demonstrated positive staining in 68.3% of the adenocarcinoma specimens (37.5%, 62.5%, 91.6%, and 75% of Stage A, B, C, and D, respectively). Patients with colorectal carcinomas exhibiting simultaneously negative and positive CD expression in malignant and stromal cells, respectively, had a worse 5-year overall survival (P < 0.05). The mean 5-year survival of the 16 patients overexpressing CD in nonneoplastic stromal cells (>15% of stromal cells positive for CD) was significantly worse in comparison with the rest of the adenocarcinomas (n = 44) (27.6 +/- 4.6 vs. 46 +/- 2.7 months, respectively, P < 0.01). CONCLUSIONS: Expression of CD immunoreactivity by the stromal cells may be associated with a more invasive phenotype. Therefore, CD expression in tumor and stromal cells may serve as an important indicator of progression and guide postoperative treatment.

Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified.

A series of 80 female patients undergoing surgery for primary breast ductal infiltrating carcinoma not otherwise specified (NOS) was immunohistochemically studied in order to verify any relationships between Proliferating Cell Nuclear Antigen (PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity, and several clinicopathological predictors. Positive PCNA scores (> 20% of strongly immunopositive malignant nuclei) were observed in neoplastic cells' nuclei in 13 tumors (16.25%) and were intimately associated with axillary nodal involvement (p = 0.0131), relatively high tumor grades (p = 0.0016), increased tumor size (p = 0.0312), and low or negative levels of estrogen receptors (p = 0.0323). HSP70 positive immunoexpression in malignant cells' cytoplasm (percentage of HSP70 immunoreactive cells > 10%) was detected in 33 samples (41.25%). It correlated significantly with presence of axillary lymph nodal metastases (p = 0.0033) and rather poor tumor differentiation (p = 0.0014), whereas an association of borderline statistical significance emerged between HSP70 immunoreactivity and high progesterone receptor status (p = 0.0637). PCNA positive immunostaining demonstrates the tumors' proliferative fraction and might be used as an indicator of increased malignant potential in breast cancer since it was associated with four adverse prognosticators. HSP70 immunodetection is a probable marker of the biological stress experienced by breast cancer cells, since it was related to relatively high tumor grades. Since both proteins may potentially predict disease outcome, their prognostic significance must be validated by direct relation to survival. A multivariate statistical analysis including the variables with which both proteins were associated will reveal any possible independent prognostic value of PCNA and HSP70 immunostaining in local, ductal invasive breast cancer NOS.

Heat shock protein 70 and HLA-DR molecules tissue expression. Prognostic implications in colorectal cancer.

PURPOSE: The expression of 70,000-Da heat shock protein (HSP 70) and HLA-DR molecules on cancer cells influences immunologic mechanisms that may be of some prognostic significance. The purpose of this study was to examine the relationship among immunohistochemical HSP 70, HLA-DR expression, and clinicopathologic tumor variables, as well as patient survival in a series of 128 colorectal carcinomas. METHOD: A three-step immunoperoxidase staining technique was undertaken for detection of both markers. RESULTS: Of the examined carcinomas 77.3 percent were HSP 70-positive and 74.2 percent were HLA-DR-positive. Increased HSP 70-positive expression correlated significantly with low differentiation (P < 0.05), showed a tendency to characterize advanced stages of disease, and was clearly associated with worse overall survival (P < 0.05). The highest rate of HLA-DR positivity was demonstrated in early stages and was significantly associated with more favorable prognosis (P < 0.001). HSP 70-positive/HLA-DR-negative patients had worse overall survival compared with the rest (P < 0.001). CONCLUSIONS: The resulting opposite effects on prognosis of examined markers seem to be related to different pathophysiologic functional roles on tumor immunology.

Prognostic significance of p53 and c-erbB-2 immunohistochemical evaluation in colorectal adenocarcinoma.

Mutant p53 tumour suppressor gene and c-erbB-2 proto-oncogene are involved in human carcinogenesis, and their protein product detection in human malignancies might influence the evolution of many neoplasms. Our aim was to estimate their association with histopathological and clinical parameters of prognostic value in colorectal cancer. An immunohistochemical assay was undertaken in formalin-fixed sections from tissue specimens of 60 colorectal carcinomas. Nuclear p53 expression was detected in 46.6%, while membranic c-erbB-2 positivity was noticed in 35% of the examined cases. P53 positivity rate significantly correlated with poor differentiation (p < 0.001), high mitotic activity (p < 0.0001), tumour stage (p < 0.001) and 5-year overall survival period (p < 0.01). C-erbB-2 positivity incidence significantly correlated with advanced Dukes' stage (p < 0.001) and high mitotic activity (p < 0.05). Significant association between p53 and c-erbB-2 immunostaining was observed (p < 0.05) and p53/c-erbB-2 co-expression was related to poor differentiation (p < 0.001), high mitotic activity (p < 0.001), advanced Dukes' stage (p < 0.001), tumour aneuploidy (p < 0.05) and worse overall survival (p < 0.05). P53 and c-erbB-2 immunohistochemical detection in combination with known prognostic indicators may be a useful future tool in determining colorectal cancer prognosis and subsequently in deciding on optimal postoperative treatments.

Significance of estrogen receptors and cathepsin D tissue detection in gastric adenocarcinoma.

Estrogen receptors (ERs) have recently been reported to be present in carcinomas of stomach, an organ that has so far been considered as nontarget for sex hormones. Cathepsin D is an estrogen-regulated lysosomal protease that has been overexpressed in breast cancer. ER and cathepsin D immunohistochemical expression were studied in this research in order to estimate their association to known histopathological and clinical parameters and their possible prognostic significance as well. Sixty-two patients with gastric adenocarcinomas were included in this study. The cancers were studied immunohistochemically concerning ER positivity in tumor cell nuclei and cathepsin D cytoplasmic expression. Nuclear ER staining was detected in tumor cells of 25% of male and 27% of female patients. ER positivity was demonstrated mainly in the well and moderately differentiated carcinomas; 87.5% of ER(+) tumors were also characterized as cathepsin D positive and a significant correlation between ER and cathepsin D positive expression was demonstrated (P < 0.05). Cytoplasmic cathepsin D expression was observed in carcinomatous cells of 70.9% of gastric tumors. Early tumor stage and good differentiation were significantly associated with increased cathepsin D expression (P < 0.05, P < 0.001). Histologic type, degree of differentiation and tumor stage were significantly correlated to survival (P < 0.05, P < 0.001 and P < 0.001). The patients who were cathepsin D(+) had a significant prognostic advantage over the cathepsin D(-) patients (P < 0.001). The presence of ER and estrogen-regulated cathepsin D indicates the involvement of sex hormonal factors in these tumors and cathepsin D positive expression in tumor cells seems to be related to better prognosis. Their biological, clinical, and prognostic roles remain to be further elucidated.

Expression of alpha-thymosins in human tissues in normal and abnormal growth.

Radioimmunoassays specific for the N and C termini of human prothymosin alpha and the N terminus of human parathymosin alpha were employed for the measurement of the levels of alpha-thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression of the two alpha-thymosins was observed in thymus (prothymosin alpha-rich) and liver (parathymosin alpha-rich). A decline in the levels of both alpha-thymosins was found with age, with prothymosin alpha in thymus showing the sharpest change (15- to 30-fold). The levels of both alpha-thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin alpha and parathymosin alpha was 17.9- and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin alpha and parathymosin alpha. These results suggest an in vivo relationship of the expression of alpha-thymosins with the human tissue cell proliferation activity.

[Cutaneous fistula of hydatid cyst of the liver]. / Fistulisation à la peau d'un kyste hydatique due foie.

We report a case of liver hydatic cyst fistulised spontaneously at the skin. It is an extremely scarce complication.

Giant cavernous hepatic hemangioma: treatment by ligation of the hepatic artery.

We present a case of a giant hepatic hemangioma. We found it at laparotomy and we decided on the course of treatment on the operating table. As right lobectomy was not feasible, we performed ligation of the hepatic artery. The patient made an uneventful recovery. A selective hepatic angiography and a liver scan were performed 8 months postoperatively and they both showed regression of the tumor. The tumor was not demonstrable in the right hepatic artery. The patient is in excellent health 2 years after the operation; the liver is smaller in palpation and the tumor itself is nonpalpable. In this case the ligation of the hepatic artery was a successful therapeutic procedure.

Role of tumor immunity in ovarian cancer.

Antigens associated with ovarian cancer tissue have been identified by the use of heteroantisera. It has also been reported that lymphocytes from patients with ovarian cancer responded to phytohemagglutinin (PHA) and keyhole-limpet hemocyanin (KLH) but had failed to respond to autologous tumor extracts. In our series, pretreatment sera from 37 patients with stage III and IV ovarian cancer failed to react with ovarian cancer antigen preparations. After therapy, serum from only three patients was reactive: all three patients were treated by chemoimmunotherapy. Preliminary data from this clinical trial for treating stage III and IV ovarian cancer with chemotherapy, immunotherapy, or combined chemoimmunotherapy show that survival of patients treated by chemotherapy or immunotherapy corresponded to that of nonresponders to L-PAM therapy as described in another study. Interestingly, combined chemoimmunotherapy produced a survival curve depicting significant improvement, similar to that for the responders to L-PAM therapy reported in that study.

Screening for breast cancer.

Mammography is of real assistance to the surgeon in evaluating breast problems not associated with a breast mass. Use of mammography in the detection of early breast cancer in breast demonstration projects has brought forth the time honored value judgement of benefit vs risk. This report introduces an additional aspect in the consideration of benefit vs risk, the interval cancer. From the demonstration project at KUMC, 326 biopsies were performed and 65 proved to be cancer. However, 24 additional women developed cancer before their next recommended screening date. This reduces the accuracy of mammography and physical examination by trained nurses in screening for breast cancer to 73%.

Tricuspid stenosis secondary to metastatic melanoma.

Cardiac metastases from malignant melanoma are frequent, usually asymptomatic and occur terminally. When responsible for symptoms, close evaluation of the patient is imperative for correct diagnosis and subsequent therapy. Surgical intervention where indicated in combination with chemotherapy and judicious use of irradiation constitutes optimal therapy.

Endodermal sinus tumor of the ovary and alpha fetoprotein: a case report.

Yolk sac tumors of the ovary are associated with elevations in serum levels of alpha fetoprotein (AFP). Thus, an antigenic marker is provided for evaluating therapeutic results in selected patients. A patient with a pure endodermal sinus tumor of the ovary is presented who underwent serial determinations of AFP. The effectiveness and limitations of serial AFP levels as demonstrated by this case are discussed in addition to the surgical and chemotherapeutic management of patients with yolk sac tumor of the ovary.

The metastatic potential of metastases: a case report.

Confirmation of the potential for metastases to metastasize in humans, especially those patients with a well controlled primary, should alter present approaches to patients with malignant disease and isolated recurrences. Reported herein is a case clearly demonstrating the metastatic potential of metastases.