Primary signet-ring cell adenocarcinoma of the uterine cervix: case report and review of the literature.

Signet-ring cell adenocarcinoma is a rare subtype of the uterine cervix; thus there are no guidelines and the prognosis is unknown. There seems to be a significant role for reporting the treatment and outcome of this rare disease in order to establish guidelines and to assist in decision-making. However, treatment should be tailored to each patient according to clinical status and disease stage. Excluding extra-genital origin is mandatory, as it will change treatment management considerably.

Total Skin Electron Irradiation and Sequential Malignancies in Mycosis Fungoides Patients: Longitudinal Study.

AIMS: To determine the role of total skin electron irradiation (TSEI) as a cause of second malignancies in mycosis fungoides patients. MATERIALS AND METHODS: Mycosis fungoides patients referred to TSEI were followed in a longitudinal study. Other diagnosed malignancies were obtained after cross-matching with the Israel National Cancer Registry database. RESULTS: Between 1974 and 2010, 197 patients were treated: 134 (68%) men, 63 (32%) women; mean age 58 ± 17years. Topical/systemic treatment was given to 134 (68%) patients. TSEI was given to 104 (68.9%) patients. Seven (4.6%) received sub-TSEI and 40 (26.5%) received focal electron irradiation fields. Forty-six (23%) patients did not receive radiotherapy. The second primaries rate was 6.7 times higher in male mycosis fungoides patients and 13.1 times higher in female mycosis fungoides patients than in the general Israeli population. Malignant melanoma developed in eight patients after radiotherapy, in one patient without irradiation. The skin-related cancer rate after irradiation versus no irradiation was higher (P = 0.018). Combination radiotherapy with psoralen + ultraviolet A and/or nitrogen mustard yielded 11 cases of skin cancer versus no cases without irradiation. CONCLUSIONS: Mycosis fungoides patients have a high incidence of sequential malignancies. TSEI is associated with higher 'skin-related cancer' rates. Close longitudinal follow-up of mycosis fungoides patients is obligatory.

Nuclear and cytoplasmic expression of ErbB-4 in prostate cancer.

PURPOSE: To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. BASIC PROCEDURES: Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using Immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0-3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). MAIN FINDINGS: Overexpression of ErbB-4 (> or = 1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was > or = 2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (< or = 1) and intermediate/high (> or = 2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. PRINCIPAL CONCLUSIONS: ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.

Curcumin synergistically potentiates the growth inhibitory and pro-apoptotic effects of celecoxib in pancreatic adenocarcinoma cells.

BACKGROUND AND AIM: Adenocarcinoma of the Pancreas is a leading cause of cancer-related mortality, accounting for an estimated 30,000 deaths per year in the United States. Multiple studies have indicated that specific cyclooxygenase-2 (COX-2) inhibitors may serve in the prevention and treatment of a variety of malignancies including pancreatic adenocarcinoma. Recent studies had shown that the long-term use of high concentration of COX-2 inhibitors is not toxic free and may be limited due to serious gastrointestinal and cardiovascular side effects. The chemopreventive efficacy of the phytochemical, curcumin has been demonstrated in several in vitro and animal models. In this study we investigated whether curcumin potentiates the growth inhibition effect of a COX-2 inhibitor (celecoxib, Pfizer, NY, USA) in human pancreatic cancer cells. METHODS: P-34 (expressing high levels of COX-2), and MIAPaCa (expressing low levels of COX-2) and Panc-1 (no expression of COX-2) evaluated cell lines were exposed to different concentrations of celecoxib (0-40 microM), curcumin (0-20 microM) and their combination. Cell viability was by XTT assay. Apoptosis was assessed by flow cytometry and COX-2 expression was measured by Western blotting analysis. RESULTS: In P-34 cells, curcumin synergistically potentiated the inhibitory effect of celecoxib on cell growth. The growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Western blot analysis showed that COX-2 expression was down-regulated by the combination therapy. CONCLUSION: Curcumin synergistically augments the growth inhibition inserted by celecoxib in pancreatic cancer cells expressing COX-2. The synergistic effect was mediated through inhibition of COX-2. This may enable the use of celecoxib at lower and safer concentrations and may pave the way for a more effective treatment in this devastating disease.

Thermoradiotherapy for residual microscopic cancer: elective or post-excisional hyperthermia and radiation therapy in the management of local-regional recurrent breast cancer.

A Phase I/II study was undertaken to investigate the efficacy and side effects of combined hyperthermia and radiation therapy in the management of presumed or known microscopic residual tumors. Between February 1985 and March 1991, 262 fields in 89 patients with local-regional recurrent breast cancer were treated with externally administered hyperthermia and radiation therapy. Thirty-eight fields were treated for microscopic residual disease following excisional biopsy of nodular recurrences and 224 fields were treated electively for areas at high risk for local recurrences adjacent to fields with macroscopic residual disease. Mechanically mapped temperatures were monitored throughout the field in all treatments. All patients had at least one follow-up evaluation at three weeks or more following completion of treatment. The majority of the fields were in patients who had had extensive prior therapy including radiation therapy (54%), chemotherapy (71%), and hormonal therapy (51%). All fields received hyperthermia (1-6 treatments: average 1.74) and radiation therapy (average dose: 42.4 Gy); concurrent hormonal therapy was administered in 37% of the treatments and no fields received concurrent chemotherapy. The treatments were well tolerated, no life-threatening complications were noted. Averages for all fields of the minimum, maximum, and average measured interstitial temperatures were 40.2 degrees C, 45.3 degrees C, and 42.8 degrees C, respectively. The three-year actuarial local-control rate for all 262 treated fields was 68%. Parameters characterizing the initial breast cancer, the patient and tumor at the time of hyperthermia, and the treatment were studied in univariate and multivariate analysis for correlation with duration of local control within the hyperthermia treatment field. Parameters in the best five covariate model correlating with the duration of local control included: estrogen receptor status of the initial breast cancer; initial T-stage; time from initial breast cancer to first failure; age at hyperthermia; and concurrent radiation dose (p-value for model less than 0.000001). Six covariate models adding anatomic site of disease, field type, mean minimum temperatures, and mean percent temperatures greater than or equal to 40 degrees C all resulted in improved models. Randomized controlled studies stratifying for these pretreatment parameters are felt warranted to confirm the value of adjuvant hyperthermia in the elective treatment of areas of high risk for local-regional recurrent breast cancer and in fields following surgical excision of recurrent disease, particularly in patients in whom full dose radiation therapy cannot be safely administered.

Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy for the treatment of carcinoma of the prostate.

PURPOSE: Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study. METHODS AND MATERIALS: From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures. RESULTS: Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively. CONCLUSION: From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.

Intrapericardial minocycline sclerosis for malignant pericardial effusion.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of minocycline hydrochloride (minocycline) intrapericardially in patients with malignant pericardial effusion. DESIGN: Consecutive patients admitted to the hospital during a 32-month period received intrapericardial minocycline. SETTING: A 900-bed university hospital. PATIENTS: Fourteen consecutive patients with malignant pericardial effusion. INTERVENTION: Following percutaneous insertion of a pericardial drain, minocycline was administered at a dosage of 10 mg/kg every 48 h until fluid drainage stopped or until further therapy was deemed necessary. MEASUREMENTS: Complications associated with therapy, total minocycline requirements, immediate and late failure of therapy, and clinical and echocardiographic follow-up of at least 6 months. RESULTS: Mean amount of minocycline administered was 1.9 +/- 1.0g given in 2.4 divided doses. Total drainage time was 5.4 +/- 2.5 days. Recurrence of malignant pericardial effusion was seen in only 1 of 14 patients. Death occurred in 10 patients due to severe metastatic disease in all. Minocycline instillation was associated with severe chest pain in seven patients, and with ECG changes suggesting pericardial or subepicardial injury in two patients. CONCLUSION: (1) Intrapericardial minocycline instillation is very effective in preventing recurrence of malignant pericardial effusion. (2) Minocycline is irritative to the pericardium and may cause severe chest pain with transient ECG changes, suggesting pericardial or subepicardial injury.

Mucosal melanoma following autologous stem cell transplantation for non-Hodgkin's lymphoma (NHL).

The incidence of secondary malignancy following autologous stem cell transplantation (ASCT) is increasing. We describe a patient with stage IVB Hodgkin's disease who developed primary amelanotic malignant melanoma of the tongue 18 months following autologous stem cell transplantation. She was treated by partial glossectomy and supra-omohyoid neck dissection followed by cytokine-mediated immunotherapy. Malignant melanoma of the skin is a frequent secondary solid tumor seen in patients undergoing stem cell transplantation. However, mucosal melanoma which is rare by itself (0.2-8%) has never been reported in NHL patients following ASCT. Early diagnosis and initiation of combined local and systemic treatments including immuno-therapy may improve the outcome of this rare but lethal complication.

Should soybean agglutinin purging be performed in breast cancer patients undergoing autologous stem cell transplantation? A retrospective analysis of 48 patients.

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has gained an increasing role in the treatment of high-risk Stage II-III and/or metastatic breast cancer patients. Several investigators reported on a high rate of tumor cells contaminating the bone marrow and peripheral blood stem cell collection. Nevertheless, the clinical implication of reinfusion of tumor cells with the stem cells to the relapse rate is still uncertain. In this retrospective analysis we compare the outcome and the toxicity of 29 patients with high-risk Stage II-III and 19 metastatic breast cancer patients who underwent HDC with ASCT. Thirteen patients underwent transplant with soybean agglutinin (SBA)-purged graft, while 35 consecutive patients received unmanipulated graft. Engraftment was significantly faster for the nonpurged transplant. No differences in disease-free survival, freedom from relapse, or overall survival were noted in both groups during a median follow up time of 14 months. We conclude that tumor cell purging using SBA in breast cancer patients is not warranted. New purging methods are needed to assess the role of tumor cell purging in breast cancer patients.

Acute pericarditis following bleomycin: a case report and literature analysis.

Acute pericarditis following bleomycin treatment is extremely rare. A case report and analysis of the literature are presented.

Malignant pericardial effusion associated with metastatic rectal cancer: case report.

Pericardial effusion caused by malignant disease is an uncommon disorder. We present a patient with rectal cancer who developed malignant pericardial effusion as the main site of relapse 18 months following surgery. We discuss the incidence and the therapy of this condition.

Radiation therapy in epidemic, AIDS-related Kaposi's sarcoma in southern Africa.

AIMS AND BACKGROUND: Acquired Immunodeficiency Syndrome (AIDS) associated Kaposi's Sarcoma (EKS) is widely spread in the Southern African Region. No large studies concerning the role of radiation therapy in the Southern African variant of EKS have been reported to date. METHODS: Over a 10 year period (1982-1992) 25 patients with EKS (disseminated skin involvement) were treated primarily with radiation therapy at the Johannesburg General Hospital. Radiation fields were individually tailored to the extent of the disease. Total administered doses ranged between 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks. RESULTS: Overall response and symptomatic relief rates were 72% and 80%, respectively. Toxicity was mild and manageable. CONCLUSIONS: Our retrospective analysis supports the use of radiation therapy for the Southern African type of EKS.

PIP: Data suggest that 10-20% of African HIV-infected persons have Kaposi's Sarcoma (KS). African epidemic, AIDS-related KS (EKS) is widespread in the southern African region, with patients often needing treatment because of the disfiguring and stigmatic nature of the disease. Cytotoxic chemotherapy has shown antitumor activity, but it may further compromise the underlying immune deficiency. EKS is, however, very radiosensitive and radiation therapy is considered to be the treatment of choice for palliation, despite the absence of large studies concerning the role of radiation therapy in the southern African variant of EKS reported to date. The authors report findings from a 1982-92 study of radiation therapy among 25 patients with EKS at the Johannesburg General Hospital. Radiation fields were individually tailored to the extent of the disease. Total administered doses ranged 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks to yield 72% and 80% overall response and symptomatic relief rates, respectively. Toxicity was mild and manageable. This retrospective analysis therefore supports the use of radiation therapy for the southern African type of EKS.

Hepatic intraarterial antibiotic therapy for resistant hepatic abscesses.

Liver abscesses present a severe problematic medical entity. The traditional treatment modality consists of surgical drainage, which cannot be accomplished in all circumstances. Other modes of therapy include systemic antibiotics or percutaneous catheter drainage under ultrasonography or computerized tomography. Despite new treatment regimes liver abscesses, to date, are a potentially lethal disease, with a mortality rate of about 50%. We report an innovative approach of high dosage intrahepatic arterial antibiotic infusion for the therapy of hepatic abscesses, which are resistant to conventional treatments. A patient who underwent mastectomy for breast carcinoma, developed liver metastases one year later. She was prescribed systemic chemotherapy for one year, but no antitumor response was evident. Since ther was no evidence for extra-hepatic metastases, intraarterial hepatic chemotherapy was instituted, using an Infusaid (Mi-400) implantable pump. Marked regression of liver metastases was observed. Therapy was withheld after 19 months because of biliary sclerosis development. At this stage, the patient developed liver abscesses, which were resistant to systemic antibiotic therapy. Intraarterial antibiotic therapy, using the implantable pump, was initiated. Following the treatment, a marked improvement in the patients' clinical condition was recorded and shrinkage of the abscesses was evident by ultrasonography. The patient was free of symptoms for three months, when she was readmitted with evidence of terminal metastatic disease and sepsis. It is suggested that intrahepatic arterial antibiotic therapy is an additional mode of treatment for patients with persistent liver abscesses which fail to respond to conventional treatment.

[Evolving role of radiation therapy in nonmalignant disorders].

Various nonmalignant disorders have traditionally been treated with radiation therapy. It has almost completely been discontinued due to reports of secondary malignancy. During the past 15 years there has been an evolving role for radiation therapy in various nonmalignant disorders such as meningioma, A-V malformation, prevention of vascular restenosis and heterotopic bone formation. Appropriate follow-up of such patients for diagnosis of secondary malignancy is recommended. Radiation therapy should be carefully considered in diseases not successfully treated with conventional means.

[Somatostatin analogue in the treatment of neuroendocrine gut tumors].

Somatostatin is a short-acting natural peptide secreted by specialized cells in the GI tract, the central and peripheral nervous systems, and a variety of other tissues. Its many actions include suppression of the secretion of GH, TSH, GI hormones, and inhibition of GI exocrine secretion. A long-acting analogue developed by Sandoz (Sandostatin, SMS 201-995) has been used to treat acromegaly and neuroendocrine tumors. We report our experience with it in carcinoid tumors (4 cases), glucagonomas (2), gastrinoma (1), VIPoma (1) and nonfunctioning islet cell tumor (1). It was given by continuous subcutaneous infusion, using a small portable pump, in doses ranging from 300 to 1500 mcg/day, without significant side-effects. 7 of the 9 patients had complete relief of symptoms, and tumoral hormone secretion decreased in 4 of the 5 in whom it was measurable, but there was no evidence of tumor regression. SMS 201-995 is useful for the symptomatic treatment of patients with neuroendocrine gut tumors.

Effect of Chinese herbal therapy on breast cancer adenocarcinoma cell lines.

Despite the widespread use of medicinal herbs to prevent and treat many diseases, including cancer, there are insufficient scientific data on the safety and efficacy of the majority of herbal therapies. The aim of this study was to assess the effect of a unique Chinese herbal therapy (CHT) from controlled manufactured concentrated powders, on an in vitro model of breast cancer. Three breast adenocarcinoma cell lines (MDA-231, MDA-453, T47D) were exposed to CHT for 72 h. Cell viability was assessed by XTT (sodium 3'-[1-(phenylaminocarbonyl)-3, 4-tetra zolium]-bis(4-methoxy-6-nitro) benzene sulphonic acid hydrate) assay. Apoptosis and cell cycle stage were determined by fluorescence-activated cell sorting (FACS) analysis. CHT decreased cell survival in a dose-dependent manner in all tested cell lines. FACS analysis of treated and non-treated T47D cells demonstrated that the inhibitory effect of CHT was associated with an increase in apoptosis. A randomized clinical trial is currently underway to investigate CHT as supplementary therapy for breast cancer patients receiving chemotherapy.