A word of caution: do not wake sleeping dogs; micrometastases of melanoma suddenly grew after progesterone treatment

Background: Hormonal treatment might affect the immune response to tumor antigens induced in cancer patients who are being vaccinated. Case presentation: A 33 years-old woman was diagnosed with cutaneous melanoma in May 2009. Her melanoma was located in the intermammary sulcus, had a Breslow thickness of 4 mm, a Clark’s level IV, it was ulcerated and highly melanotic. The bilateral sentinel node biopsy was negative. She entered into a randomized Phase II/III clinical study comparing a vaccine composed of irradiated melanoma cells plus BCG plus GM-CSF versus IFN-alpha 2b and she was assigned to the vaccine arm. During the two years treatment she remained disease-free; the final CAT scan being performed in August 2011. Between November and December 2011, her gynecologist treated her with three cycles of 200 mg progesterone/day for ten days, every two weeks, for ovary dysfunction. In November 2011 the patient returned to the Hospital for clinical and imaging evaluation and no evidence of disease was found. At the next visit in March 2012 an ultrasound revealed multiple, large metastases in the liver. A CAT scan confirmed the presence of liver, adrenal glands and spleen metastases. A needle biopsy of a liver lesion revealed metastatic melanoma of similar characteristics to the original tumor. We suggest that progesterone treatment triggered proliferation of so far dormant micrometastases that were controlled during CSF470 vaccine treatment. Conclusion: The use of progesterone in patients with melanoma that are under immunological treatments should be carefully considered, since progesterone could modify the balance of pro-inflammatory and Th1 functions to a regulatory and anti-inflammatory profile of the immune system that could have an impact in tumor progression.Fil: Mordoh, Jose. Fundacion Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tapia, Ivana Jaqueline. Fundacion Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrio, Maria Marcela. Fundacion Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20–41) and 285 days (range 50–1240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients. © 2000 Cancer Research Campaig

The Hybrid SPECT/CT as an Additional Lymphatic Mapping Tool in Patients with Breast Cancer

Background Conventional lymphoscintigraphy does not always define the exact anatomic location of a sentinel node. The lymphatic drainage pattern may be unusual or may not be shown at all. The recently introduced hybrid SPECT/CT imaging could help overcome these difficulties. SPECT is a tomographic version of conventional lymphoscintigraphy and the images have better contrast and resolution. When fused with the anatomical details provided by CT into one image, a meaningful surgical ‘‘roadmap’’ can be created. So far, there is little literature on the use of hybrid SPECT/CT in lymphatic mapping in patients with breast cancer. The purpose of this review was to report on these publications, including our own experience, focusing on patient selection, SPECT/CT settings, anatomic localization, and the detection of additional sentinel nodes. Methods The majority of investigators did not formulate indications for additional SPECT/CT after conventional imaging but scanned all patients eligible for sentinel node biopsy. The SPECT/CT settings used in the studies of this review were mostly similar, but the methods used for conventional imaging were more variable. Results All studies demonstrated an improved anatomical localization by performing additional SPECT/CT; sentinel nodes outside the axilla or nodes close to the injection sit

Primary malignant melanoma of the stomach: report of a case

We report a case of primary malignant melanoma (MM) of the stomach. The patient, a 73-year-old man, was referred to our hospital for investigation of an elevated lesion in the stomach, detected by gastroscopy. On admission, physical examinations and laboratory data were unremarkable. Gastroscopy revealed a pigmented, elevated tumor, approximately 2 cm in diameter, in the posterior wall of the stomach. A biopsy was taken, which resulted in a diagnosis of MM, based on the presence of melanin in tumor cells. F-18 fluorodeoxyglucose positron emission tomography showed no accumulation of tracer except for the tumor in the stomach, indicating that it was a primary MM of the stomach. The patient underwent distal gastrectomy, but died of recurrence 1 year later. Very few cases of primary MM of the stomach have been reported. Thus, we report this case, followed by a review of the literature

Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre

<p>Abstract</p> <p>Background</p> <p>The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma.</p> <p>Patients and methods</p> <p>60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) ± D-actimomycin; 74 HILPs (G-B) with true HT (40–41.8°C) plus L-PAM (10 mg/lt) ± D-act; 108 HILPs (G-C) with true HT plus L-PAM (10 mg/lt) ± D-act plus L-PAM (5 mg/lt) additional bolus.</p> <p>Results</p> <p>Limb toxicity was very low in G-A and in G-B; increasing toxicity (grade III = 37%) in G-C; no grade IV statistical difference was registered in all three groups, with percentage values among 1.6% and 2.7%. Systemic toxicity showed itself only in the haemopoietic parameters. No differences were registered in G-B vs G-A group. In G-C vs G-B a significative increase of systemic toxicity was seen in grade 3 (p < 0.05). Postoperative complications were acceptable. Local and systemic side-effects were transient; no permanent neurological limb deficit was registered. The postoperative mortality was recorded in 3/182 HILPs (1.6%) of the G-B and G-C groups.</p> <p>Conclusion</p> <p>These data suggested that the technical implementations reduced the occurrence and the severity of the side effects and complications. The essential requirement for HILP is the quality assurance of the procedures. Although higher regional and systemic toxicity were observed in the G-C group caused by L-PAM additional bolus, the safeness of the procedures under the true hyperthermal regimen and the time increase of the high L-PAM concentration have assured the treatment reliability along with the increased clinical efficacy expectations of the treatments.</p

Factors associated with use of breast cancer screening services by women aged ≥ 40 years in Korea: The Third Korea National Health and Nutrition Examination Survey 2005 (KNHANES III)

<p>Abstract</p> <p>Background</p> <p>Despite evidence that breast cancer screening reduces morbidity and mortality, until recently most women have not undergone regular mammogram examinations in Korea. We aimed to identify factors associated with use of breast cancer screening services.</p> <p>Methods</p> <p>The Health Promotion Knowledge, Attitude and Practice survey (HP-KAP survey) is part of the Third Korea National Health and Nutrition Examination Survey 2005 (KNHANES III), a nationwide health survey in Korea. Of 7,802 individuals who participated in the HP-KAP survey, 4,292 were female. Of these, 2,583 were women aged at least 40 years and without a history of breast cancer; these women were included in this study. Information about breast cancer screening participation was obtained from the responses to questionnaires. The overall rate of regular breast cancer screening was measured. Factors that affect participation in a breast cancer screening program were identified using multiple logistic regression analysis.</p> <p>Results</p> <p>Among women aged at least 40 years, 30.4% complied with breast screening recommendations. Age of at least 65 years (adjusted odds ratio, aOR 0.61, 95% CI: 0.42-0.88), education level (no [ref], elementary school [aOR 1.51, 95% CI: 1.06-1.47], middle/high school [aOR 1.99, 95% CI: 1.36-2.92], university/higher [aOR 2.73, 95% CI: 1.71-4.35]), private health insurance (aOR 1.42, 95% CI: 1.71-4.35), attitude towards screening tests (aOR 0.18, 95% CI: 0.14-0.23), self-reported health status of 'fair' (aOR 1.26 95% CI: 1.00-1.58), and smoking (aOR 0.52, 95% CI: 0.35-0.79) were associated with the rate of regular breast cancer screening</p> <p>Conclusions</p> <p>To increase the nationwide breast cancer screening rate, more attention should be given to underrepresented groups, particularly the elderly, those with a low education level, smokers, and those with a negative attitude towards screening tests. These issues highlight the need for a new emphasis in health education, promotional campaigns and public health policy aimed at these underrepresented groups.</p

Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines

BACKGROUND: The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines. METHODS: Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan(® )Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells. RESULTS: Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway. CONCLUSION: We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence of IFN-γ-mediated HLA class I expression in ESTDAB-159 cells is due to epigenetic blocking of IFN-regulatory factor 1 (IRF-1) transactivation

Melanoma Patients with Positive Sentinel Nodes Who Did Not Undergo Completion Lymphadenectomy: A Multi-Institutional Study

Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45875/1/10434_2006_Article_10237.pd