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N A Fenske

Publications and source records attributed to N A Fenske.

At least 19 recordsLinked to original sources

Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy.

BACKGROUND: Electroporation is a process that causes a transient increase in the permeability of cell membranes. It can be used to increase the intracellular concentration of chemotherapeutic agents in tumor cells (electrochemotherapy; ECT). A clinical study was initiated to determine if this mode of treatment would be effective against certain primary and metastatic cutaneous malignancies. A group of six patients, three with malignant melanoma, two with basal cell carcinoma, and one with metastatic adenocarcinoma, were enrolled in the study. the treatment was administered in a two-step process. METHODS: Each patient received a 10 unit/m2 dose of bleomycin administered intravenously at 1 to 1.5 units/minute. This was followed by eight 99 microsecond pulses at an amplitude of 1.3 kV/cm administered directly to the tumors 5 to 15 minutes after the bleomycin was completely infused. Pulses were administered after the injection of 1% lidocaine solution around the treatment site. RESULTS: Two of three melanoma patients had objective responses. In these two patients, five of six treated tumors decreased in size, and three completely responded. Untreated tumors displayed continued growth. Objective responses were observed in both basal cell carcinoma (BCC) patients. One patient had partial responses in both treated tumors. The other patient had one of four primary BCCs respond completely, and the remaining three respond partially. Patients with metastatic breast adenocarcinoma showed complete responses in both treated nodules after ECT. All patients tolerated the treatment well with no residual effects from the electric pulses. CONCLUSIONS: ECT was an effective local treatment in the majority of nodules treated. The results thus far are very encouraging and the study is being continued.

Adenocarcinoma

Cutaneous manifestations and consequences of smoking.

Cigarette smoking is strongly linked to serious internal diseases such as cancer, cardiovascular disease, and lung disease. However, the external manifestations and consequences of smoking are relatively unknown. Although generally less ominous, the cutaneous manifestations of smoking may be associated with significant morbidity. This article reviews the known adverse effects on the skin of smoking.

Humans

Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome: spontaneous remission in a 15-year-old girl.

Acanthosis nigricans is associated with many diseases, including internal malignancies, genetic disorders, and endocrine abnormalities. Insulin resistance frequently accompanies endocrine-associated acanthosis nigricans. We describe a patient with acanthosis nigricans associated with hyperandrogenism and extreme insulin resistance that spontaneously resolved after a marked decrease in insulin receptor antibodies.

Acanthosis Nigricans

Bleomycin-mediated electrochemotherapy of basal cell carcinoma.

BACKGROUND: A new technique, electroporation, enhances the antitumor effects of a variety of chemotherapeutic agents. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy. Exposure of cancerous tissues to pulses of electricity during electrochemotherapy appears to increase cell membrane permeability and thus intracellular access to cytotoxic drugs. Electrochemotherapy has been shown to have potent antitumor activity in a variety of in vitro studies, animal tumor models, as well as in clinical trials with squamous cell carcinomas of the head and neck. OBJECTIVE: The purpose of the study was to determine the effects of bleomycin-mediated electrochemotherapy on several basal cell carcinomas (BCCs) in two patients with nevoid BCC syndrome. METHODS: Electrical pulses were delivered to tumor nodules by means of caliper electrodes after systemic doses of bleomycin were administered. Vital signs were closely monitored during application of the electrical pulses. RESULTS: Partial responses were observed in tumors from both of the patients treated with electrochemotherapy; three partial responses were observed in one patient, and one partial response was observed in the other patient. Complete responses were seen in two lesions. Only minimal local or systemic side effects were noted in response to the therapy. CONCLUSION: To our knowledge, this is the first study that documents the effects of bleomycin-mediated electrochemotherapy on BCC. Studies are ongoing with intralesional bleomycin during electrochemotherapy to see whether additional antitumour effects can be produced in patients with BCC by this route of administration.

Adult

The use of intraoperative radiolymphoscintigraphy for sentinel node biopsy in patients with malignant melanoma.

BACKGROUND: Selective lymphadenectomy or "sentinel node" biopsy has been introduced recently by Morton and colleagues (Arch Surg 1992;127:392-9) to stage patients with intermediate and thick malignant melanomas. It has proven to be an effective way to identify nodal basins at risk for metastasis without the morbidity of a complete lymph node dissection. The majority of biopsies can be performed under local anesthesia with small incisions, but technical difficulties occasionally result in unsuccessful explorations. Identification of the sentinel node can be enhanced by a intraoperative radiolymphoscintigraphy, a technique introduced Alex and Krag (Surg Oncol 1993;137-43) that uses radiolabeled sulfur colloid and a hand-held gamma probe. OBJECTIVE: We used intraoperative radiolymphoscintigraphy in conjunction with 1% lymphazurin blue dye to define the sentinel node(s) in 148 patients with greater than 0.76 mm in thickness or Clark level IV melanomas. Sentinel lymph nodes were isolated, harvested, and examined using conventional histopathology, and immunohistochemistry for S-100 and HMB-45 antibodies. RESULTS: The overall success rate of sentinel lymph node localization was 97% using a combination of the two techniques. Twenty-one (14%) patients had micrometastasis, and 17 of these subsequently underwent complete lymph node dissection. A total of 220 of 275 (80%) sentinel nodes harvested were radioactive or "hot" compared with 165 of 275 (60%) with the blue dye alone. Four of the patients with micrometastasis had sentinel nodes positive by gamma probe, but negative by blue dye mapping techniques. CONCLUSION: Our results suggest that intraoperative radiolymphoscintigraphy using a hand-held gamma detecting probe improves the identification of sentinel lymph nodes during selective lymphadenectomy. This may reduce the number of "unsuccessful explorations" using the vital blue dye technique for lymphatic mapping, and appeal to a greater variety of surgeons, including dermatologic surgeons.

Biopsy

Bleomycin-mediated electrochemotherapy of metastatic melanoma.

BACKGROUND: Electroporation is a new technique that enhances the antitumor effects of chemotherapy by exposing cancerous tissues to pulses of electricity. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy (ECT). The electric pulses increase cell membrane permeability and thus intracellular access. Electrochemotherapy has been shown to have potent antitumor activity in a number of in vitro studies, several animal models, and clinical trials with squamous cell carcinomas and basal cell carcinomas. OBJECTIVE: To report the effects of ECT in 5 patients with metastatic malignant melanoma. RESULTS: Twenty-three lesions of metastatic melanoma were treated with intralesional bleomycin sulfate followed by pulses of electricity. Pulses were delivered via caliper or needle electrodes placed around the tumor. Complete responses were observed in 18 tumors (78%) and partial responses were seen in 4 (17%). No responses were seen in lesions treated with either pulses or bleomycin alone. Vital signs were closely monitored during the procedure, and minimal side effects were noted. CONCLUSIONS: This is the first study that documents the antitumor effects of ECT in metastatic melanoma. Although not a cure, it may be an effective alternative to palliative surgery or irradiation in these patients.

Adult

The clinical spectrum of actinic elastosis.

A plethora of literature promoting our understanding of the differences between intrinsic (chronologic) aging versus extrinsic aging of the skin has been published during the last two decades. The predominant extrinsic factor is UV radiation; the functional, histologic, and clinical consequences are referred to as photoaging, or dermatoheliosis. Actinic elastosis refers specifically to the degenerative histologic alterations seen by light microscopy in sun-damaged skin. Multiple factors, including anatomic site, extent of sun exposure, and other physical or environmental factors affect the clinical appearance of these changes. We review the clinical spectrum of the actinic elastotic variants.

Humans

Herpes zoster and internal malignancy.

Herpes zoster (HZ) often occurs concomitantly with various internal malignancies, most commonly hematologic in origin. Authors in the past proposed that HZ was a marker for internal malignancy, since it is often found in association with a malignancy. A critical review of the literature revealed that when HZ and malignancy occur in the same individual, rarely does HZ precede the malignancy, but usually follows it. Many studies have evaluated HZ in cancer patients, but only three studies have evaluated the occurrence of malignancy after the diagnosis of HZ, and all found no increased incidence of internal malignancy in patients with HZ. Since HZ is a poor marker for internal malignancy, extensive workups to find occult malignancy are not indicated. In rare cases, however, HZ precedes a malignancy. We therefore recommend a baseline history and physical examination, with further directed workup only if there are abnormal findings.

Child

The razor blade biopsy technique. Introduction of the adaptor-designed shave biopsy instrument.

BACKGROUND: Several years ago, the razor blade was introduced as an alternative device for performing the shave removal and/or biopsy of skin lesions. Though inexpensive and readily available, the razor blade is somewhat cumbersome to use and poses a risk for accidental injury to the practitioner. OBJECTIVE: We describe a modification of the razor blade shave biopsy procedure utilizing an innovative adaptor design. METHODS: A comparison of the adaptor-designed shave biopsy instrument to the standard razor blade device is made. RESULTS: The modifications implemented in the adaptor design serve to enhance the comfort of performing biopsies, minimize accidental injury, help save time, and provide for a more professional appearing way in which to obtain skin specimens. CONCLUSION: The new adaptor design helps to facilitate the safe and effective use of the razor blade in dermatologic practice.

Biopsy

Merkel cell carcinoma. Diagnosis and treatment.

BACKGROUND: Merkel cell carcinoma is an uncommon malignancy of the skin that often portends a poor prognosis. Since its first description by Toker in 1972, a plethora of case reports and articles regarding the etiopathogenesis and treatment have been published spanning multiple medical and surgical disciplines. Much confusion still exists regarding the diagnosis and treatment of this ominous tumor. OBJECT: Through extensive review of the medical, surgical, and pathological literature, to collate the observations of multiple investigators and summarize these findings. METHODS: Articles from journals of multiple subspecialties were carefully reviewed with particular emphasis placed on epidemiology, prognosis, histology, immunohistochemistry, electron microscopy, tumor origin, treatment, and work-up of Merkel cell carcinoma. RESULTS: Merkel cell carcinoma is an aggressive malignant neoplasm. Local recurrence develops in 26-44% of patients despite therapy. Up to three-fourths of patients eventually develop regional nodal metastases with distant metastases occurring in one-third of all patients. Reported overall 5-year survival rates range from 30% to 64%. CONCLUSION: Treatment recommendations unfortunately are based more on anecdotal than scientific data because of the rarity of the tumor and its recognized high risk. Most authors recommend wide local excision of the primary lesion and regional lymph node resection if lymph nodes are palpable followed by x-irradiation of both the postsurgical bed and lymph node basin. The role of elective lymph node resection in the absence of clinically positive nodes remains controversial.

Carcinoma, Merkel Cell

The role of selective lymphadenectomy in the management of patients with malignant melanoma.

BACKGROUND: A novel surgical technique based on selective lymphadenectomy was used to stage 132 patients with intermediate and thick cutaneous malignant melanoma. Preoperative and intraoperative lymph node mapping techniques were used to ascertain regional lymph node basins at risk for metastasis, and to identify the first node(s) the afferent lymphatics encounter in the basin, defined as the "sentinel" node(s). It has been shown that the histology of the sentinel node reflects the histology of the rest of the nodal bain, and according to preliminary studies using this technique, the likelihood of bypassing the sentinel node(s) to "higher" level nodes is less than 2%. Epidemiologic studies indicate that the long-term survival of patients with melanomas of intermediate thickness or greater is significantly compromised if regional lymph nodes are involved. Yet, the utility of performing lymph node dissections for the purposes of staging only is controversial, not only because of the morbidity and expense of the procedure, but the lack of proven survival benefit. OBJECTIVE: In the present study, we performed preoperative and intraoperative lymphatic mapping, harvested clinically normal sentinel nodes, and examined them for micrometastasis by light microscopy. Both conventional stains and immunocytochemistry for S-100 protein and HMB-45 antibodies were performed, and only those patients with documented micrometastasis received complete lymph node dissections. RESULTS: The sentinel node(s) was identified in each of the patients. Micrometastatic disease was detected in 31 (23%) of the patients by selective lymphadenectomy, and the sentinel node(s) was the only node involved in 83% of the cases upon subsequent complete nodal dissection. CONCLUSION: Our preliminary results suggest that selective lymphadenectomy following lymphatic mapping is an effective procedure for staging melanoma patients with lesions of intermediate thickness or greater. Our results indicate that sentinel lymph nodes may be successfully identified and harvested in the majority of patients, and that they may be examined for the first evidence of micrometastasis without the need of a complete nodal dissection. Information as to whether micrometastases are present in the sentinel node would be valuable in staging patients, and identifying candidates for complete nodal dissections. We are participating in a National Cancer Institute-sponsored multicenter trial to ascertain whether this surgical approach can impact on the recurrence rate and survival of patients with stage 1 and 2 melanoma.

Adolescent

Immunohistochemical assessment of tumor vascularity in recurrent Clark II melanomas using antibody to type IV collagen.

Thin melanomas, measuring 0.76 mm or less, are generally associated with an excellent prognosis. However, a certain subset of these seemingly innocuous lesions have been reported to develop recurrences. Therefore, the predictive values of currently accepted prognostic indicators have been questioned in thin melanomas. Several studies concerning tumor vascularity in melanoma and certain non-melanocytic malignancies suggest that the degree of vascularization correlates with growth rate and biologic aggressiveness. In the present study, we determined the vascularity of a small group of Clark level II melanomas that resulted in recurrence, and compared these results to an equal number of nonrecurrent lesions with similar prognostic indicators. Blood vessels were labeled by immunoperoxidase staining techniques for Type IV collagen, and quantified by image analysis. No statistical difference was found between the two groups when mean blood vessel counts and percent vascular area were measured. The recurrent tumors had a mean PVA of 4.68 compared to 4.34 for the nonrecurrent group (p = 0.677). The mean blood vessel count beneath the recurrent group was 29.6 per 400 x field, and the corresponding value for the nonrecurrent group was 31.8 (p = 0.681). Our data is preliminary within this limited group of tumors, yet it suggests that tumor vascularity is not a distinctive prognostic indicator by which eventual outcome can be predicted in thin Clark level II malignant melanomas.

Adult

Atypical beta 2-microglobulin amyloidosis following short-term hemodialysis.

A 47-year-old white female renal transplant recipient presented complaining of "wrinkles" that predominantly involved the palmar aspect of her fingers. Light-microscopic examination of biopsy material obtained from affected areas revealed deposits of amorphous, hyaline material in the reticular dermis that contrasted sharply with collagen and elastic fibers. Examination by transmission electron microscopy disclosed a mass of fibrils recognizable as amyloid, despite negative histochemical staining with both Congo red and crystal violet. Immunoperoxidase staining for beta 2-microglobulin was positive. Along with an elevated serum beta 2-microglobulin level, this finding supported the diagnosis of hemodialysis-induced amyloidosis (HIA). Unusual features of our case include lesion location, short duration of antecedent hemodialysis therapy, and negative staining for amyloid using conventional staining techniques.

Amyloidosis