Operative morbidity and risk factor assessment in melanoma patients undergoing inguinal lymph node dissection.

A series of 168 patients who underwent 177 inguinal lymph node dissections from 1979 to 1989 were retrospectively reviewed to determine the incidence and severity of postoperative complications as well as the perioperative risk factors associated with them. Operative mortality was 0%, whereas the incidence of moderate to severe wound infection was 11%, skin flap problems 0%, seromas 6%, and hemorrhage 3%. The occurrence of a wound complication increased the average hospital stay from 11 to 12 days. Multivariate risk factor analysis revealed age older than 50, male sex, and smoking to be significant risk factors for developing a wound infection. The use of prophylactic antibiotics and the duration of closed suction catheter drainage were not predictive of wound complications. Overall, 44% of patients experienced some postoperative edema, with only 7% of patients having 1+ edema that lasted longer than 6 months. Combined ilioinguinal lymph node dissection increased the chance of developing moderate to severe edema. These risk factors identify patients at high risk for morbidity, which should lead to improved perioperative care.     

Surgical management and prognostic factors in patients with subungual melanoma.

OBJECTIVE: Forty-six cases of subungual melanoma were reviewed to identify significant clinicopathologic prognostic factors, determine the role of DNA content analysis in the biologic assessment of these tumors, and evaluate the effectiveness of amputation level, lymph node dissection (LND), and regional limb perfusion on the survival of these patients. BACKGROUND: Subungual melanoma is a unique and rare subtype of melanoma, constituting only 1% to 3% of cases. Thus, little is known about prognostic factors and optimal management of patients with this disease. Moreover, the appropriate level of amputation and LND and limb perfusion in the management of subungual melanoma remain controversial. METHODS: Forty-six patients underwent amputation alone or in combination with LND and/or regional limb perfusion for primary subungual melanoma. The effects of these treatment modalities and the prognostic significance of patient and tumor-related variables, including DNA flow cytometric data, on overall survival were assessed. RESULTS: Univariate statistical analysis identified six factors that significantly affected patient survival. They were stage at diagnosis (p = 0.0001), percentage of aneuploid cells (p = 0.01), presence of ulceration (p = 0.02) or bone invasion (p = 0.02), thickness of the primary lesion (p = 0.03), and percentage of cells in S-phase (p = 0.03). Multivariate analyses identified tumor stage and S-phase fraction as independent prognostic factors in these patients. Survival did not differ among patients who received amputation alone or those who underwent amputation in combination with LND or perfusion (p = 0.90); however, the use of limb perfusion reduced the incidence of locally recurrent disease. The level of amputation did not affect patient survival (p = 0.74) or the incidence of local recurrence. CONCLUSIONS: The study identified several significant prognostic factors, including DNA flow cytometric parameters, in patients with subungual melanoma. In addition, it showed that conservative amputation of the affected digit at the level of the proximal interphalangeal or metacarpophalangeal/metatarsophalangeal joint appears to be safe, provided that clear margins are obtained. Although isolated limb perfusion may reduce the incidence of local recurrence, LND, or limb perfusion in the routine management of subungual melanoma remains controversial.     

Predicting survival and recurrence in localized melanoma: A multivariate approach

Several clinical and pathologic factors appear to affect melanoma recurrence and survival. While much attention has been directed at identifying prognostic factors, few researchers have developed predictive models for survival and recurrence. Two major clinical questions are of interest in the management of melanoma: 1) what is the patient's chance of surviving for a given period, e.g., 5 or 10 years, after diagnosis of melanoma; and 2) after a patient has been disease free for a period of time, e.g., 5 years, what is his or her chance of melanoma recurrence or death in the following interval, e.g., 5 years or 10 years. In this paper, a generalized multivariate prognostic model to address both of these clinical questions is presented.Tables of the estimated probabilities of melanoma recurrence and death for prognostic subgroups are shown to facilitate prediction of an individual patient's outcome. The model was based on a database of 4,568 patients with localized melanoma, one of the largest melanoma databases in the world with detailed clinical and pathologic information, and long-term follow-up. Tumor thickness at diagnosis was the single most important prognostic factor for all outcomes. Tumor ulceration, Clark's level, lesion location, and sex had an impact on overall survival from diagnosis for some of the subgroups defined by tumor thickness. Tumor thickness at diagnosis was strongly indicative of melanoma recurrence and death even after a disease free interval of 2, 5, or 10 years. Lesion location and ulceration were of prognostic importance after disease free intervals up to 5 years, but their impact on melanoma recurrence and death diminished after longer disease free intervals.Prediction models for melanoma outcome at diagnosis and after a disease free period can provide useful information to clinicians in the management of melanoma patients. Utilization of the model will be valuable in identifying patients at high risk for melanoma recurrence and death.

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Resumen Diversos factores clínicos y patológicos parecen afectar las tasas de recurrencia y mortalidad del melanoma. En tanto que se ha dispensado bastante atención en cuanto a identificar factores de pronóstico, pocos investigadores han desarrollado modelos de predicción de sobrevida y de recurrencia. Dos interrogantes principales son de interés en cuanto al manejo del melanoma: 1) cual es la probabilidad del paciente de sobrevivir un determinado período, por ejemplo 5 o 10 años, después del diagnóstico de melanoma; y 2) después de que el paciente se ha mantenido libre de enfermedad por un período de tiempo, por ejemplo 5 años, cual es su probabilidad de recurrencia del melanoma o de muerte en el siguiente período de tiempo, por ejemplo 5 o 10 años. En este artículo se presenta un modelo generalizado y multivariable de pronóstico para enfrentar estos interrogantes clínicos.Se presentan tablas para estimar las probabilidades de recurrencia y de muerte en divesos subgrupos de pronóstico que facilitan la predicción del destino final de un individuo. El modelo se fundamentó en una base de datos de 4568 pacientes con melanomas localizado, una de las más grandes bases de datos de melanoma existentes en el mundo, con detallada información clínica y patológica y con seguimiento a largo plazo. El espesor del tumor en el momento del diagnóstico apareció como el factor individual de pronóstico de mayor importancia. La ulceración del tumor, el nivel de Clark, la ubicación de la lesión y el sexo exhibieron importancia en cuanto a la sobrevida para algunos de los subgrupos definidos según el espesor del tumor. El espesor del tumor en el momento del diagnóstico fue un factor fuertemente indicativo de recurrencia y de muerte, aún después de un intervalo libre de enfermedad de 2, 5 o 10 años. La ubicación de la lesión y la ulceración aparecieron como de importancia en cuanto el pronóstico después de intervalos libres de enfermedad hasta de 5 años, pero tal importancia disminuyó después de intervalos libres de enfermedad de mayor duración.Los modelos de predicción del resultado final en el melanoma aplicados en el momento del diagnóstico y después de un período libre de enfermedad pueden proveer información útil para el manejo clínico de pacientes con melanomas. La utilización del modelo es de valor en la identificación de pacientes con mayor riesgo de recurrencia y muerte por melanoma.

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Résumé Plusieurs facteurs cliniques et anatomopathologiques semblent déterminer la récidive et la survie des mélanomes. De nombreux auteurs se sont intéressés à l'identidification des facteurs de pronostic, mais peu d'équipes ont essayé d'élaborer un modèle permettant de prédire survie et récidive. Deux problèmes restent à résoudre dans le traitement des mélanomes: 1) quelles sont les chances de survie après le diagnostic de mélanome pour un patient donné, pendant une période donnée, par exemple 5 à 10 ans et 2) quels sont les risques de récidive ou de décès dans les 5 à 10 ans qui suivent une période donnée (par exemple 5 ans) où un patient semblait en rémission. Dans cet article, nous avons créé un modèle d'évaluation pronostique multifactorielle pour tenter de répondre à ces 2 questions.Des tables montrant les probabilités de récidive et de décès par mélanome, calculées à partir de sous groupes différents, peuvent aider à déterminer le pronostic. Ce modèle repose sur une banque de données de 4568 patients atteints de mélanome non disséminé. Il s'agit d'une des plus grandes banques de données au monde contenant des informations cliniques, anatomopathologiques et sur l'évolution à long terme. L'épaisseur de la tumeur au moment du diagnostic était le facteur pronostic le plus important pour déterminer l'évolution. Le caractère ulcéré, le stade de Clark, la localisation de la lésion et le sexe avaient tous une importance pronostique, influant sur la survie globale liée à l'épaisseur de la tumeur. L'importance de l'épaisseur de la tumeur au moment du diagnostic était un facteur de récidive et mortalité même après un intervalle long de 2, 5 ou 10 ans. Le site de la tumeur et son caractère ulcéré étaient également des facteurs associés à un risque de récidive tumorale ou de décès après une rémission de 5 ans. L'influence de ces facteurs diminuait en cas de rémission plus prolongée.Les modèles permettant d'évaluer l'évolution du mélanome malin au moment du diagnostic et apreès un intervalle de rémission sont utiles au cours du traitement du mélanome. Ils doivent permettre d'identifier les patients à risque de récidive et de décès.

     

Economic impact of reducing hospitalization for mastectomy patients.

In 1985, two policies designed to reduce hospitalization charges for mastectomy patients were instituted at the M.D. Anderson Cancer Center at Houston. The first was a policy of "same-day" admissions for elective surgery patients, and the second was early postoperative discharge for mastectomy patients with suction catheter drains in place. The economic savings resulting from these policies was analyzed by comparing demographics, operation, stage of disease, hospital stay, hospital charges, and complications for two groups of patients. Fifty-nine consecutive mastectomy patients treated between 1983 and 1984, before these policy changes, had "standard management" consisting of hospital admission 24 hours before surgery and discharge only after the surgical drains were removed. Sixty-one consecutive mastectomy patients treated between 1986 and 1987, after these policy changes went into effect, were admitted from the recovery room after surgery and were discharged with drainage catheters in place, usually within 72 hours. All operations were performed by the same faculty surgeon as a representative experience of the General Surgery faculty. The average hospital stay was reduced from 10.5 to 4.3 days. A mean 39% reduction in hospital charges (from $4867.00 to $2981.00) was achieved by instituting the policies of "same-day" admission and early postoperative discharge with drainage catheters in place. Complication rates were not changed. Implementation of this policy resulted in an estimated savings of $750,000.00 in the hospital care of approximately 400 patients treated at the M.D. Anderson Cancer Center at Houston each year. Adjustments in patient care delivery systems from a predominantly inpatient to an outpatient setting required changes in outpatient nursing responsibilities (although not in new personnel). Patient education and written instructions for home care of surgical wounds and drainage catheters were essential for implementing an early discharge policy. With these facts in mind, hospital admission on the day of operation and early postoperative discharge with drainage catheters in place should be the goal for most mastectomy patients.     

Telemedicine and distributed medical intelligence.

Recent trends in health care informatics and telemedicine indicate that systems are being developed with a primary focus on technology and business, not on the process of medicine itself. The authors present a new model of health care information, distributed medical intelligence, which promotes the development of an integrative medical communication system addressing the process of providing expert medical knowledge to the point of need. The model incorporates audio, video, high-resolution still images, and virtual reality applications into an integrated medical communications network. Three components of the model (care portals, Docking Station, and the bridge) are described. The implementation of this model at the East Carolina University School of Medicine is also outlined.     

A human B cell differentiation antigen selectively expressed on mature B cells identified by a monoclonal antibody (HB-2)

A monoclonal IgM antibody (HB-2), produced against a membrane antigen on the Raji, B cell line, reacted by indirect immunofluorescence with 2 to 40% of lymphoblasts from the B cell lines, Raji, Daudi, SN-1036, and SB but not with other types of cell lines, including pre-B, myeloid, melanoma, or T cells. HB-2 antibody reacted with 10 ± 3% of normal blood mononuclear cells, and was unreactive with monocytes, granulocytes, platelets, or erythrocytes. Two-color immunofluorescence revealed that HB-2 antigen expression was confined to cells bearing surface Ig. An interesting finding was the fact that 25% of plasmablasts induced by pokeweed mitogen also expressed the HB-2 antigen. However, pre-B and plasma cells from normal bone marrow did not express the HB-2 antigen either on their membrane surface or in their cytoplasm. Analysis of 85 leukemias revealed that the HB-2 antigen was expressed on acute and chronic B cell leukemias and Burkitt's lymphomas, but not on malignacies of pre-B, T, myelocytic, or plasma cells. The results suggest that expression of the HB-2 antigen is confined to mature B cells.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.