Heriberto Medina-Franco

Multimodality Treatment of Merkel Cell Carcinoma: Case Series and Literature Review of 1024 Cases

Background: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options.Methods: The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher’s exact test. Significance was defined as P < .05.Results: MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001).Conclusions: MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

Factors Associated With Local Recurrence After Skin-Sparing Mastectomy and Immediate Breast Reconstruction for Invasive Breast Cancer

ObjectiveTo examine the incidence of local recurrence (LR) and factors associated with it in a population of patients who underwent skin-sparing mastectomy (SSM) and immediate reconstruction for invasive carcinoma. Summary Background DataThe efficacy of SSM has been challenged by concerns about increased risks of LR. MethodsA consecutive series of 173 patients (176 cancers) with invasive carcinoma underwent SSM and immediate breast reconstruction (June 1986 to December 1997). Data were analyzed by the Kaplan-Meier method, the log-rank statistic test, and the Cox proportional hazards model. ResultsMean patient age was 47 ± 9 years (27% were 40 or younger). The AJCC stages were 1 = 43%, 2 = 52%, and 3 = 5%. Thirty percent of tumors were poorly differentiated. With a median follow-up of 73 months, the LR rate was 4.5%. The mean local relapse-free interval was 26 months. Seventy-five percent of patients who presented with LR developed distant metastases and died of disease within a mean of 21 months. On univariate analysis, factors associated with higher LR rate were tumor stage 2 or 3, tumor size larger than 2 cm, node-positive disease, and poor tumor differentiation. Actuarial 1-, 3-, and 5-year overall survival rates were 98%, 94%, and 88%, respectively. On multivariate analysis, factors associated with decreased survival were advanced stage, presence of LR, and absence of hormone therapy. LR was a highly significant predictor of tumor-related death. ConclusionsThere is a low incidence of LR after SSM, and it is associated with advanced disease at presentation. LR is an independent risk factor for tumor-related death.

Radioguided occult lesion localization (ROLL) versus wire-guided lumpectomy for non-palpable breast lesions: A randomized prospective evaluation

It is important to optimize the localization technique for non‐palpable breast lesions.

Clinicopathologic characteristics of gastric cancer in a young patient population

The aim of this study was to analyze the clinicopathologic characteristics of young patients with gastric cancer with special attention to hereditary gastric cancer in a tertiary referral university hospital. Charts from all patients 40 years of age or younger at the time of diagnosis, during the period from January 1, 1987 to December 31, 2001, were retrospectively reviewed. Demographic variables, family history of gastric cancer, clinicopathologic characteristics, and treatment-related variables were analyzed. Overall survival was the main outcome variable. Survival curves were constructed by means of the Kaplan-Meier method, univariate anlaysis was performed with the log-rank test, and multivariate analysis with Cox regression. Significance was considered at P<0.05. During the study period, 558 cases of gastric cancer were seen at our institution, 83 (14.8%) were in patients 40 years of age or younger. Mean patient age was 33.2 years. Forty-five patients (54.2%) were male. Fourteen patients (16.9%) had a family history of gastric cancer. Five patients (6%) fulfilled the criteria of hereditary gastric cancer. Surgery was performed in 88% of patients, but only 35% of the operations had a curative intent. Operative mortality was 2.4%. On univariate analysis, advanced tumor stage, hypoalbuminemia, low performance status, diffuse type, pangastric tumor location, noncurative surgery, and lack of adjuvant chemotherapy had a significant negative impact on survival. On multivariate analysis, advanced tumor stage, pangastric tumor location, and absence of adjuvant chemotherapy were significantly associated with poor prognosis. Family history of gastric cancer or hereditary gastric cancer did not have any impact on prognosis. There is a high frequency of gastric cancer in young patients at our institution. Most patients present in advanced stages, which favors a poor overall survival. Family history of gastric cancer or hereditary gastric cancer did not have a significant impact on survival. Complete resection and adjuvant chemotherapy appeared to confer the only chance of prolonged survival.

Sentinel Node Biopsy for Cutaneous Melanoma in the Head and Neck

AbstractBackground: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area. Methods: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fisher’s exact test was used for comparisons. Significance was defined as P < .05. Results: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%. Conclusions: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

Pancreaticoduodenectomy for metastatic tumors to the periampullary region

Although operative resection of metastatic lesions to the liver, lung, and brain has proved to be useful, only recently have there been a few reports of pancreaticoduodenectomies in selected cases of metastases to the periampullary region. In this report we present four cases of proven metastatic disease to the periampullary region in which the lesions were treated by pancreaticoduodenectomy. Metastatic tumors corresponded to a melanoma of unknown primary site, choriocarcinoma, high-grade liposarcoma of the leg, and a small cell cancer of the lung. All four patients survived the operation and had no major complications. Two patients died of recurrence of their tumors, 6 and 63 months, respectively, after operation; the other two patients are alive 21 and 12 months, respectively, after operation. It can be inferred from this small but documented experience, as well as a review of the literature, that pancreaticoduodenectomy for metastatic disease can be considered in selected patients, as long as this operation is performed by experienced surgeons who have achieved minimal or no morbidity and mortality with it.

Astemizole Synergizes Calcitriol Antiproliferative Activity by Inhibiting CYP24A1 and Upregulating VDR: A Novel Approach for Breast Cancer Therapy

Background Calcitriol antiproliferative effects include inhibition of the oncogenic ether-à-go-go-1 potassium channel (Eag1) expression, which is necessary for cell cycle progression and tumorigenesis. Astemizole, a new promising antineoplastic drug, targets Eag1 by blocking ion currents. Herein, we characterized the interaction between calcitriol and astemizole as well as their conjoint antiproliferative action in SUM-229PE, T-47D and primary tumor-derived breast cancer cells. Methodology/Principal Findings Molecular markers were studied by immunocytochemistry, Western blot and real time PCR. Inhibitory concentrations were determined by dose-response curves and metabolic activity assays. At clinically achievable drug concentrations, synergistic antiproliferative interaction was observed between calcitriol and astemizole, as calculated by combination index analysis (CI <1). Astemizole significantly enhanced calcitriol’s growth-inhibitory effects (3–11 folds, P<0.01). Mean IC20 values were 1.82±2.41 nM and 1.62±0.75 µM; for calcitriol (in estrogen receptor negative cells) and astemizole, respectively. Real time PCR showed that both drugs alone downregulated, while simultaneous treatment further reduced Ki-67 and Eag1 gene expression (P<0.05). Astemizole inhibited basal and calcitriol-induced CYP24A1 and CYP3A4 mRNA expression (cytochromes involved in calcitriol and astemizole degradation) in breast and hepatoma cancer cells, respectively, while upregulated vitamin D receptor (VDR) expression. Conclusions/Significance Astemizole synergized calcitriol antiproliferative effects by downregulating CYP24A1, upregulating VDR and targeting Eag1. This study provides insight into the molecular mechanisms involved in astemizole-calcitriol combined antineoplastic effect, offering scientific support to test both compounds in combination in further preclinical and clinical studies of neoplasms expressing VDR and Eag1. VDR-negative tumors might also be sensitized to calcitriol antineoplastic effects by the use of astemizole. Herein we suggest a novel combined adjuvant therapy for the management of VDR/Eag1-expressing breast cancer tumors. Since astemizole improves calcitriol bioavailability and activity, decreased calcitriol dosing is advised for conjoint administration.

Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: A potential new therapeutic approach

BackgroundApproximately 30% of breast tumors do not express the estrogen receptor (ER) α, which is necessary for endocrine therapy approaches. Studies are ongoing in order to restore ERα expression in ERα-negative breast cancer. The aim of the present study was to determine if calcitriol induces ERα expression in ER-negative breast cancer cells, thus restoring antiestrogen responses.MethodsCultured cells derived from ERα-negative breast tumors and an ERα-negative breast cancer cell line (SUM-229PE) were treated with calcitriol and ERα expression was assessed by real time PCR and western blots. The ERα functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were assessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-à-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical analyses were determined by one-way ANOVA.ResultsCalcitriol was able to induce the expression of a functional ERα in ER-negative breast cancer cells. This effect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly, the calcitriol-induced ERα restored the response to antiestrogens by inhibiting cell proliferation. In addition, calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell proliferation regulators CCND1 and EAG1.ConclusionsCalcitriol induced the expression of ERα and restored the response to antiestrogens in ERα-negative breast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic strategy in ERα-negative breast cancer patients.

Anorectal melanoma: report of three cases with extended follow-up.

Primary anorectal melanoma is rare. There is controversy regarding the best surgical treatment because of its poor prognosis. Three cases with extended follow-up are reported in this article. A 53-year-old woman with rectal bleeding was diagnosed with a melanoma of the rectum and underwent an abdominoperineal resection. The patient died with distant metastases 8 months later. An 80-year-old woman with rectal bleeding was diagnosed with a melanoma of the rectum and underwent a transanal local excision. She remains alive 4 years later but with locally recurrent disease. A 78-year-old man with rectal bleeding was diagnosed with a melanoma of the rectum and underwent an abdominoperineal resection. He died with local and metastatic disease 25 months later. Recent trends favor local excision when technically feasible, although some patients may require an abdominoperineal resection of the rectum, especially for larger tumors.

Radioguided Localization of Clinically Occult Breast Lesions (ROLL): A Pilot Study

Abstract:  Management of nonpalpable breast lesions requiring pathologic diagnosis has been with wire localization during the last few decades. Recently, radioguided localization (ROLL) became an alternative for this type of lesions. The objective of the present study was to evaluate the feasibility of this technique in a tertiary referral center in Mexico City. Consecutive patients requiring pathologic diagnosis from a nonpalpable breast lesion were included in the present study. On the same day of operation, all patients were injected with particles of human serum albumin. Localization of the lesion was performed in the operation theater with the aid of a hand‐held gamma‐probe. All lesions were identified in a control x‐ray of the surgical specimen. Demographic, clinical, surgical and pathologic data were recorded. Forty patients with a mean age of 56.8 ± 7.8 years were included. In 39 of the 40 patients (97.5%) the “hot spot” was identified easily. In all patients, the area of maximum radioactivity corresponded to the site of the lesion. Imaging confirmation of the lesion in the surgical specimen was done during the first excision in 37 patients (92.5%). In the remaining cases (7.5%), a wider excision was performed during the same procedure, finding the suspected lesion in all cases. Diagnosis of cancer was made in seven patients, (17.5%). There were no significant surgical complications. Our data suggest that ROLL offer a simple and reliable method to localize occult breast lesions, allowing complete removal of the lesion in 100% of the patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and the medical staff, producing less discomfort in patients than wire localization.