Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Increased tight junctional permeability is associated with the development of colon cancer.

Epithelial tissues act as barriers between two fluid compartments, and the epithelial barrier function is provided by the epithelial cells and the tight junctions (TJs) that connect them. We have shown previously that chronic treatment of a cultured epithelial monolayer with phorbol ester tumor promoters induces an increase in transepithelial paracellular permeability and produces tumor-like polyps, suggesting an association between TJ permeability and tumor formation. In this study, we analyzed the association between TJ permeability and formation of tumors in vivo. The permeability of the TJs was assessed in normal human and rat colon epithelia and in colon tumors by measuring the transepithelial electrical resistance, the paracellular flux rate of D-[(14)C]mannitol and the electron microscopic evaluation of the penetration of the electron dense dye ruthenium red across the TJs. By these criteria, the TJs of human colon tumors, including carcinomas and adenomatous polyps, and the TJs of 1,2-dimethylhydrazine (DMH)-induced rat colon tumors were leakier than the TJs of normal colon. Treatment of rats with the carcinogen DMH induced a progressive increase in the number of aberrant colonic crypts, considered the putative pre-neoplastic colonic phenotype while increasing TJ permeability of the colon epithelium prior to the development of tumors. These results showed that increased TJ permeability of the colon epithelium and consequently a decrease in epithelial barrier function precede the development of colon tumors.

Paget's disease of the male breast.

A histopathologically proven case of Paget's disease of the breast in a 47-year-old male induced a review of the 32 cases in the world's literature. Paget's disease usually presents in the 5th and 6th decades of life without any obvious racial predilections. The most frequent presenting signs include ulceration, eczema, nipple discharge, bleeding, and crust formation. At the time of presentation, 50 per cent of the patients have a palpable breast mass, positive lymph nodes, or both. When entertaining the diagnosis of Paget's disease of the breast using morphologic characteristics of the cells, the diagnosis of malignant melanoma and Bowen's disease (intraepithelial squamous cell carcinoma) must be included in the differential diagnosis. Certain differences will be seen between these three entities based on specific cell staining and the uptake of certain tumor markers. There is no evidence that this disease behaves differently in males versus females, but the 5-year survival for males is worse: 20 to 30 per cent in males versus 30 to 50 per cent in females. The treatment of this disease must focus on the pathology of the underlying tumor. Current treatment involves modified radical mastectomy or radical mastectomy for Stage I and II tumors. Adjuvant chemotherapy, radiation, and tamoxifen are also used depending on the nodal and receptor status of the tumor.

The effect of Fe3+ ion on benzylpenicillin in micellar and nonmicellar aqueous solutions.

The effect of Fe3+ ions on the hydrolysis of benzylpenicillin in aqueous solution below and above the critical micellar concentration (c.m.c. = 0.26 M) has been studied. The catalytic effect of Fe3+ ions on hydrolysis of this drug has been demonstrated; the reaction rate constant, calculated from UV absorption data of non-micellar solutions, decreases with concentration. It is likely that Fe3+ ions form complexes with the products of degradation. The bright brown slightly soluble product formed in micellar solutions was analyzed by UV - Vis reflection, IR and mass spectroscopy and, in agreement with the results of elemental analysis, is postulated to be an octahedral binuclear complex, Fe2BP4(OH)2. This study has been linked with the clinical observation that prolonged treatment with penicillin leads to anemia.

Cerebral hydatid cyst in children. Experience of 27 cases.

The authors present 27 cases of cerebral hydatid cyst (CHCy) treated between 1980 and 1992. These cases of CHCy represent 2.8% of all cases of expansive nontraumatic lesions in children. Most of the patients were between 6 and 10 years of age. There was a substantial prevalence of male patients-18 cases (66.6%). Most of the children with CHCy were from rural areas. The cysts were all located in the cerebral hemispheres (none in the posterior fossa). Usually two or three lobes were affected and the cysts were most often retrorolandic. Only 8 patients (29.6%) also had pulmonary or hepatic infestation. All patients were operated on immediately the diagnosis was established. Operative mortality was very low (1 patient died immediately after surgery). There have been 11 cases of recurrence; all these patients have been reoperated on. Neurological sequelae were mainly partial and general seizures. Epilepsy developed postoperatively in five patients. Paresis, which usually disappears in time, was the most common motor disturbance. Two other important postoperative complications were subdural effusion and ventricular dilatation (six cases). There have been five cases of multiple recurrences (four of these patients have since died). Treatment with albendazole was used in three cases without significant results.

Chronic post thoracotomy pain.

Chronic post-thoracotomy pain (CPP) is a vexing clinical problem whose management has received scant attention. In order to identify the risk factors associated with CPP and determine the optimal treatment, the records of 238 consecutive patients who underwent thoracotomy were reviewed. CPP was defined as discomfort requiring the regular administration of analgesics that continued more than three months following surgery. CPP was present in 25 (11%) patients: 10/20 (50%) chest wall resections, 5/25 (20%) pleurectomies, 10/193 (5%) pulmonary resections. Among the 23 patients who required preoperative narcotics, 12 (52%) developed CPP. Improved pain control and decreased narcotic use was achieved via the administration of nonsteroidal anti-inflammatory medication and tricyclic anti-depressants. In addition, 10/25 patients required 11 pain procedures: trigger-point injection, intercostal blocks, injections of epidural steroids, stellate ganglion block. Recurrent pain occurred in 20 patients following initial control. All were found to have tumor regrowth. We conclude that CPP occurs more commonly following chest-wall resection and pleurectomy, and that preoperative narcotic use is a predictor of CPP. Worsening pain following initial relief should prompt a vigorous search for recurrent cancer.

Morbidity after intraperitoneal insertion of saline-filled tissue expanders for small bowel exclusion from radiotherapy treatment fields: a prospective four year experience with 34 patients.

UNLABELLED: When prolonged small bowel exclusion (SBE) from external radiotherapy (RT) fields or immediate exclusion of bowel from brachytherapy sources is required for a patient without adequate omentum, there are no simple proven methods available for accomplishing these goals. We report a prospective study of SBE by intraperitoneal, saline-filled tissue expanders (TE). Thirty-four patients had exclusion of small bowel from either external radiotherapy (RT) ports (20), afterloading catheter treatment fields (5), both (5), or from intracavitary implants (4). Twenty-seven TEs were placed in the pelvis and 7 in the iliolumbar fossa. TE volume ranged from 400-1500 cc (median 550 cc). Patients had rectal (n = 15), colon (6), endometrial (4), anal (3), and vaginal (1) cancers and sarcomas (5). Fifteen patients had recurrent neoplasms, 13 of which were in previously irradiated fields. Nine patients had colorectostomies directly behind the TE, and 12 had other bowel (6) or ureteral (3) anastomoses or bladder repairs (3) adjacent to the TE. RESULTS: TEs remained in the patients from 6 to 173 days (median 95). Morbidity included three early TE withdrawals before RT was begun, one for a prolonged ileus, one for a perineal wound dehiscence, and one for an unrelated small bowel obstruction. Two patients (5.9%) early in the series had post-withdrawal complications (non-lethal small bowel fistulas requiring reoperation), although in a recent cohort of patients no post-withdrawal complications occurred using a different placement technique (0/17 vs. 2/14, P = 0.2). The patient injury complication rate was 4/34 (11.8%). None of these limited or delayed RT, but RT was limited to less than that planned in one other by TE deflation (total complication rate 14.7%). There were no clinical infections involving the prostheses, even though one patient had an abdominal wound dehiscence, 3 had pelvic abscesses, and 2 had exposure of the TE through the vagina (1 planned, 1 at dehisced vaginal cuff) after TE placement. We noted no acute and one possible late RT complication in these patients (18 months median follow-up, range 3-43 months). Small bowel was displaced from > 95 per cent of the RT treatment volume in 70 per cent and from > 75 per cent of the treatment volume in 89 per cent of 27 evaluable patients treated with external RT. CONCLUSION: Intraperitoneal placement of a saline-filled tissue expander is a simple, safe and effective means of small bowel exclusion from RT portals.

Isolated locally recurrent rectal cancer: a review of incidence, presentation, and management.

Locoregional recurrence after treatment for rectal cancer may be largely prevented by wide pelvic surgical margins, adjuvant radiotherapy, and chemotherapy. Approximately half of these recurrences will present with recurrence only at the surgical site; one third to one half will be resectable with conventional surgical procedures, but the rest will require extended resections, including sacrum and hypogastric vessels, to achieve clean margins. Only a small fraction of those treated will be cured. There is no proof that radiotherapy or chemotherapy added to surgical excision afford better results, since no trials have been or are likely to occur, given the rarity of the situation. However, best results seem to follow multimodality therapy using complete surgical resection and radiotherapy (IORT or brachytherapy with or without teletherapy) with chemopotentiation. Yet, there is no multimodality series with a sufficient number of patients and follow-up period to be able to distinguish the actual value of the treatment and which patients are most likely to benefit. It is important to note that there will be some patients with second LRR who can be further aided by aggressive locoregional therapy.

Primary leiomyosarcoma of the greater omentum: case report and review of the literature.

Omental leiomyosarcomas are rare intra-abdominal tumors. This report describes a case of primary leiomyosarcoma of the greater omentum discovered on abdominal CT scan. The mass was removed via laparotomy and an omentectomy performed. At 2 years postoperatively there is no sign of tumor recurrence or metastasis.

Heterotopic mucinous cystadenoma of the pancreas.

A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue.

DNA content in correlation with postsurgical stage in non-small cell lung cancer.

The relationship between DNA content, TNM stage, tumor size, grade, histology, and disease-free survival was assessed in a retrospective study of patients with non-small cell lung cancer who had undergone resection and complete mediastinal lymph node dissection. Flow cytometric analysis was performed on paraffin-embedded tissue of 90 consecutive patients. The patients were analyzed both as a group and by individual stage. Median follow-up was 11 months (range, 1 to 35 months). Aneuploid tumors were not significantly different from diploid tumors with regard to pathologic TNM stage (p = 0.34), size (p = 0.5), grade (p = 0.5), or histology (p = 0.34). Disease-free survival of patients with aneuploid tumors was not significantly different than that of patients whose tumors had normal DNA content (p = 0.69). DNA content did not correlate with established prognostic factors in patients with non-small cell lung cancer who underwent resection and complete mediastinal lymph node dissection.

Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement.

A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication.

Contribution of patient history to the glutathione S-transferase activity of human lung, breast and colon tissue.

Overexpression of the glutathione S-transferases (GSTs) and their involvement in the detoxification of anticancer agents has prompted numerous investigations of the enzyme activity of human tumor tissue. This study represents an in-depth evaluation of the contribution of patient history and pathological status to the GST activity of various human tissues. GST activity was elevated significantly in tumors of the lung, breast and colon as compared to unmatched and matched normal tissue from the same organ. The GST activity of primary breast tumors varied significantly with the stage of the tumor. Breast tumors previously treated with both radiation and chemotherapy had significantly lower levels of GST activity than untreated tumors. Neither progesterone nor estrogen receptor content was associated with the GST activity in primary breast tumors. Colon metastases possessed higher levels of GST activity than primary colon tumors but enzyme activity was independent of the Duke's classification of the tumor. Only tumors of the left colon had levels of GST activity that were higher than those of adjacent normal mucosa. No relationship was evident between either age or sex and the GST activity of any of the tissues examined. GST activity levels may reflect the site-specific ability of tissues to provide cellular protection against xenobiotics.

A technique for liver biopsy performed in Pekin ducks using anesthesia with Telazol.

Infection of Pekin ducks with duck hepatitis B virus is a useful model for studying the hepadenoviruses, of which human hepatitis B virus is the prototype. The utility of this model has been limited, however, by the difficulties associated with anesthetizing and obtaining liver biopsies from ducks. We developed a technique using Telazol (13 mg/kg) to anesthetize ducks before surgical biopsy of the liver in ducks infected with duck hepatitis B virus. Eight Pekin ducks infected with duck hepatitis B virus underwent serial biopsies at 4- to 5-week intervals. There was one perioperative death in 34 surgical procedures with no evidence on intra-abdominal sepsis or wound complications. Telazol can be used safely and humanely to anesthetized ducks without the need for general endotracheal anesthesia.

Lymphokine-activated killer cell suppressor factor in malignant effusions.

We examined the possibility that tumor-released products inhibit lymphokine-activated killer cell activation. Lymphokine-activated killer cells from human peripheral blood lymphocytes were activated with recombinant interleukin 2 for 4 days in the presence of malignant effusions or conditioned media from cultured cell lines (10% vol/vol). Eight of 10 malignant effusions/media suppressed the induction of lymphokine-activated killer cell cytotoxicity, as measured in a 4-hour sodium chromate release assay. Seven of 10 effusions/media inhibited lymphokine-activated killer cell proliferation. Suppression was both dose and time dependent. A representative suppressive effusion was fractionated by agarose gel chromatography, treated with detergents disruptive of ionic bonds and lipids, and refractionated using polyacrylamide gel chromatography. Seven suppressive fractions ranging in molecular weight from 1 x 10(5) to 3 x 10(5) d were isolated. It is speculated that this suppressor factor may represent a large multimeric structure with ionic-bonded individual suppressive components.

Malignant mesothelioma of the tunica vaginalis testis.

Malignant mesothelioma of the tunica vaginalis is an extremely rare tumor. Appropriate treatment consists of inquinal orchiectomy with close followup. Treatment of locally recurrent malignant mesothelioma of the tunica vaginalis has not been standardized. We recommend radical resection for the initial presentation of locally recurrent disease rather than saving surgical resection as salvage therapy after other treatment modalities have failed. We report case 37 of malignant mesothelioma of the tunica vaginalis and review the literature.

Successful heart transplantation in recipients with recent preoperative pulmonary emboli.

Acute pulmonary embolus (less than 6 weeks old) has been considered an absolute contraindication to heart transplantation for fear of the potential problems of lung abscess, empyema, bronchopleural fistula, and systemic sepsis in an immunosuppressed patient. It is difficult to adhere to this principle because 30% to 50% of patients with dilated cardiomyopathy may have an acute pulmonary embolus and would be excluded from transplantation. Several centers have considered such patients for heart transplantation if they are young, on maximal medical therapy, and in extremis. The surgical management of the postoperative pulmonary problems can include bronchoscopy, antibiotics, surgical drainage, decortication, and pulmonary resection with or without muscle flaps. We describe our approach to two such patients who were managed successfully with lobectomies and latissimus dorsi muscle flaps to seal the bronchus and fill the pleural space.