Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

BACKGROUND: Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. METHODS: A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. RESULTS: Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. CONCLUSIONS: In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

Carbon dye histologically confirms the identity of sentinel lymph nodes in cutaneous melanoma.

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.

Hopelessness predicts mortality in older Mexican and European Americans.

OBJECTIVE: The purpose of this study was to evaluate the relationship between hopelessness and mortality in a biethnic cohort of older community-dwelling Mexican Americans, the most rapidly growing segment of the elderly, and European Americans. METHODS: A total of 795 persons aged 64 to 79 years completed an English or Spanish version of the 30-item Geriatric Depression Scale on entering the San Antonio Longitudinal Study of Aging, an epidemiologic survey, between 1992 and 1996. Women constituted 58% and Mexican Americans 54% of this randomly selected sample. Subjects who answered "no" to the item "Are you hopeful about the future?" were classified as hopeless. RESULTS: As of August 1999, 29% of the 73 hopeless subjects had died, compared with 11% of the hopeful, a highly significant difference. The mortality rates for cardiovascular disease and cancer were significantly greater among the hopeless subjects (7%) than among the hopeful (3%). Hopelessness predicted all-cause mortality in a Cox proportional hazards model adjusted for age, ethnic background, current smoking status, number of comorbid medical conditions, self-rated health, and frequency of social contacts (risk ratio = 2.23, 95% confidence interval = 1.33 to 3.76, p = .0026). Neither sex nor probable depression was a significant predictor of mortality in this model. CONCLUSION: These findings, together with those of others, suggest that hopelessness is a significant predictor of mortality in older and middle-aged adults of various ethnic backgrounds. Further research is needed to evaluate the mechanisms that underlie this phenomenon and the effects of treating hopelessness on the quality and duration of subjects' lives.

Does sentinel lymphadenectomy improve staging and alter therapy in elderly women with breast cancer?

BACKGROUND: Routine axillary lymph node dissection (ALND) for elderly women with invasive breast cancer has been questioned because it rarely alters therapy yet carries a significant morbidity rate. Sentinel lymphadenectomy (SLND) improves axillary staging and alters therapy in women with T1 breast cancer, but it is not clear whether SLND alters therapy in elderly women with breast cancer. METHODS: A prospective breast cancer data base was used to identify women 70 years old and older who underwent SLND for axillary staging of invasive breast cancer between 1991 and 1998. RESULTS: There were 75 invasive breast cancers in 73 women. The mean patient age was 74.5 years (range, 70-90 years). Median tumor size was 1.4 cm (range, 0.1-6.2 cm). Of the 75 tumors, 42 (56%) had favorable primary characteristics; the remaining tumors had unfavorable characteristics. SLND was performed alone in 17 cases (23%) and was followed by completion ALND in 58 cases (77%). Positive lymph nodes were identified in 32 cases (43%); 26 (81.3%) were detected by hematoxylin and eosin stains, and 6 (18.7%) were detected by immunohistochemistry alone. Five patients (6.9%) received adjuvant chemotherapy. Seven patients (9.6%) received axillary/supraclavicular radiation for positive nodes. Ten (13.7%) of 73 patients had obvious alterations in therapy because of axillary nodal status. As a result of SLND, 3 (13.6%) of 22 patients with tumors 1.0 cm or smaller received tamoxifen, and 7 (15%) of 46 patients with tumors between 1.0 and 3.0 cm in size had changes in therapy. When patient and tumor characteristics were analyzed to determine relationships to therapeutic decision-making, nodal status was the variable most significantly associated with changes in therapy (P = .0001). CONCLUSIONS: SLND improves axillary staging in elderly women with invasive breast cancer. Results of immunohistochemistry do not alter therapy in this group of individuals (P = .6367). In patients with small primary tumors, SLND alters therapy by increasing the number of patients receiving tamoxifen. In addition, SLND affects adjuvant systemic chemotherapy and regional radiotherapy in a significant number of patients with larger tumors, particularly tumors between 1.0 and 3.0 cm.

Intraoperative examination of the sentinel lymph node for breast carcinoma staging.

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Long-term survival after complete resection of melanoma metastatic to the adrenal gland.

BACKGROUND: Survival of patients with American Joint Committee on Cancer stage IV melanoma is generally poor, although there are occasional long-term survivors who have undergone surgical resection of a limited number of metastases. In the study, we examined the outcome of patients with adrenal gland metastases. METHODS: Eighty-three patients with adrenal metastases were identified from our computerized melanoma database of 8250 patients. Univariate and multivariate analyses for overall survival differences were performed by using proportional hazards modeling. RESULTS: Median survival for the 83 patients was 9.3 months (1-67 months). Of the 27 patients who underwent surgical exploration, 18 (66%) were rendered clinically free of disease by adrenalectomy alone (12 cases) or by adrenalectomy and resection of additional disease (6 cases). Nine patients underwent palliative adrenal resection. Median survival was 25.7 months after complete resection compared with 9.2 months after palliative resection (P = .02). CONCLUSIONS: Patients with adrenal metastases from melanoma, either isolated or with a limited number of additional metastases, may benefit from surgical resection if all visible disease can be removed. Patients with unresectable extra-adrenal disease achieve no survival benefit from adrenalectomy.

Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group.

OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Metastasectomy for recurrent stage IV melanoma.

BACKGROUND AND OBJECTIVES: Many patients undergoing complete surgical resection of distant metastatic melanoma (American Joint Committee on Cancer [AJCC] stage IV) develop recurrent disease. We examined whether a second metastasectomy could prolong the survival of patients with recurrent stage IV melanoma. DESIGN AND PATIENTS: Retrospective review of our 8,750-patient melanoma database identified 211 patients who were rendered clinically free of disease by surgical resection of stage IV metastases during the 24-year study period (January 1971 through December 1995). Our study population comprised the 131 patients who developed recurrent stage IV disease and were followed for at least 24 months or until death. RESULTS: The median disease-free interval prior to recurrent stage IV disease was 8 months (range 0.6-91.8 months). There were 131 tumor-involved anatomic sites; the median number was one (range 1-3). Of these sites, 71 (54.2%) were soft tissue, 35 (26.7%) were pulmonary, 28 (21.4%) were gastrointestinal, 23 (17.6%) were cerebral, 13 (9.9%) were skeletal, and 2 (1.5%) were gynecologic. Median survival following treatment for recurrent stage IV melanoma was 18.2 months after complete metastasectomy, compared with 12.5 months or 5.9 months after a palliative surgical procedure or nonsurgical management, respectively. The 5-year survival rate was 20.0% (8/40) for patients in the complete surgical metastasectomy group, compared with 7.0% (3/43) and 2.1% (1/48) for those in the palliative surgical and nonsurgical groups, respectively. By multivariate analysis, the two most important prognostic factors for survival following diagnosis of recurrent stage IV melanoma were a prolonged disease-free interval to recurrence (P = 0.0001) and complete surgical metastasectomy of the recurrence (P = 0.0001). CONCLUSIONS: Metastasectomy can prolong the survival of patients with recurrent stage IV melanoma if all clinically evident tumor can be resected.

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.

Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases.

BACKGROUND: This study was conducted to document the rate, duration, and type of objective response to active specific immunotherapy with a polyvalent melanoma cell vaccine (PMCV) for patients with in-transit melanoma metastases and to identify any acute or chronic toxic effects of PMCV treatment. METHODS: An analysis was conducted of all in-transit melanoma patients seen at the John Wayne Cancer Institute in Santa Monica, California, during the period 1985-1997 who were enrolled in prospective PMCV protocols in the absence of other therapies with possible antitumor activity (n = 54). Clinical response to PMCV was assessed by standard criteria. Survival curves were estimated by the Kaplan-Meier method. Toxicity was graded according to the Eastern Cooperative Oncology Group standard. RESULTS: PMCV produced a 17% (9 of 54 patients) objective response rate with a 13% rate (7 of 54 patients) of complete remission (CR). The median duration of CR was >22 months. Complete response lasting more than 1 year was observed in 4 patients (7.2%); 1 patient remained in remission over 9 years. Median survival was >53 months (i.e., not reached) for responders, 42 months for nonresponders, and 53 months overall. Salvage interventions allowed reinduction with PMCV in 23 of 25 patients, who subsequently remained clinically free of disease for a median of 14 months. Overall toxicity was mild, easily tolerable, and did not significantly change the quality of life. There were no toxic deaths. CONCLUSIONS: PMCV can cause objective complete regression of measurable intransit metastatic melanoma with minimal toxicity, and may prolong patients' median survival.

Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma.

BACKGROUND: Routine elective superficial parotidectomy for patients with primary cutaneous melanomas of the scalp, auricle, or face has been questioned. We evaluated an alternative, i.e., lymphatic mapping and sentinel lymphadenectomy, for patients with primary cutaneous melanomas draining to the region of the parotid gland. PATIENTS: Retrospective review of our large (>8000 patients) melanoma database identified 39 patients with primary melanomas (American Joint Committee on Cancer stage I or II) of the scalp (n = 19), auricle (n = 11), or face (n = 9) who underwent intraoperative lymphatic mapping to identify a sentinel node (SN) in the region of the parotid gland, between June 1985 and July 1997. RESULTS: A SN was identified in the parotid region of 37 patients (94.9%), four of whom had SN metastases. The mean number of SN obtained was 2.3/patient (range, 1-4/patient). The two patients (5.1%) for whom a parotid-region SN could not be identified underwent superficial parotidectomy during the same operation. Among the 33 patients with tumor-free SN, with a median follow-up period of 33.2 months (range, 1-121 months), there was one (3.1%) intraparotid recurrence; thus, the false-negative rate was 3.1%. The procedure-related surgical morbidity rate was only 2.6% (one case of temporary facial nerve paresis). CONCLUSIONS: For patients with primary melanomas of the scalp, auricle, or face, sentinel lymphadenectomy can be performed accurately in the parotid region and offers a low-morbidity alternative to routine elective superficial parotidectomy.

Tumor doubling time: a selection factor for pulmonary resection of metastatic melanoma.

BACKGROUND AND OBJECTIVES: Melanoma patients have a 20-27% rate of 5-year survival after surgical resection of pulmonary metastases. We evaluated tumor doubling time (TDT) and other prognostic factors in an attempt to identify candidates for pulmonary metastasectomy. METHODS: Review of our large melanoma database identified 129 patients who underwent complete or partial resection of pulmonary metastases. At least two preoperative chest roentgenograms were available for 45 patients; these images were used by a single examiner to measure tumor width and length. The mean of the diameters was plotted against time on semilogarithmic paper: the slope of the line approximated tumor growth rate, and TDT was proportional to the inverse of the tumor growth rate. RESULTS: For the 45 patients with a calculated TDT, median survival was 23.1 months and 5-year survival rate was 15.6% (7/45). By multivariate analysis, the only prognostically significant factors were TDT (P=0.006) and type of pulmonary resection (P=0.022). When TDT was <60 days, median survival was 16.0 months, and 5-year survival rate was zero; when TDT was > or = 60 days, median survival was 29.2 months (log-rank test; significant at P < 0.0001) and 5-year survival rate was 20.7% (6/29) (P < 0.0001). CONCLUSIONS: TDT is the most significant preoperative prognostic factor for patients undergoing pulmonary resection of metastatic melanoma. If TDT is <60 days, a preoperative neoadjuvant regimen of chemotherapy and biologic therapy is recommended. Pulmonary metastasectomy should not be attempted if TDT cannot be increased to > or = 60 days by systemic therapy.

2-Hydroxydesipramine and desipramine plasma levels: how are they related to antidepressant response?

Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder (MDD) completed a 5-week trial of desipramine following a week of single-blind placebo. Five had a past history of hypomanic disorder. For all but one patient, daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of 168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final 17-item Hamilton depression rating < and = 6 and were classified as responders. According to receiver operating characteristics analysis, patients with plasma 2-OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact test), while patients with plasma desipramine levels > and = 64 ng/ml were more likely to respond than those with lower levels (p = 0.032, Fisher's exact test). Results using an alternate response criterion were similar. These findings suggest that in desipramine-treated outpatients with primary MDD the relationship between therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for desipramine.

Psychoactive substance use disorder in relatives of patients with anorexia nervosa.

We assessed the lifetime prevalence and morbid risk of psychoactive substance use disorder (SUD; alcoholism and drug use disorder) in the first- and second-degree relatives, excluding children, of 34 female patients with anorexia nervosa (AN) and 34 age- and sex-matched controls who had no history of an eating disorder. Diagnoses of relatives were made blind to probands' diagnoses. The prevalence of SUD was 9% in both anorectic and control relatives, and the figures for morbid risk were 14% and 15%, respectively; these differences were nonsignificant. These results suggest that adolescent and adult women with AN do not possess many of the familial factors that predispose to the development of psychoactive SUD.

Depression in the elderly.

Depression in the elderly can be difficult to diagnose but often responds well to treatment. In treating late-life depression, we have the satisfaction not only of relieving our patients' distress but very likely of prolonging their lives as well.

2-Hydroxydesipramine and desipramine plasma levels and electrocardiographic effects in depressed younger adults.

Desipramine was given to 34 outpatients aged 20 to 51 years who had primary major depressive disorder but who were otherwise in good health. Daily dosage at bedtime was constant for the final 3 weeks of the 5-week study (mean, [SD] 169.1 [46.1] mg). Electrocardiograms done predrug and after 5 weeks were read by a cardiologist blind to the order in which they were performed. Plasma samples drawn 14 hours after the final study dose were assayed by high performance liquid chromatography; mean (SD) levels were 140.2 (140.0) ng/ml for desipramine and 56.5 (29.4) ng/ml for 2-hydroxydesipramine (2-OH-DMI). Heart rate and PR, QRS and QTc intervals were significantly greater at the end of the study than at baseline, while QT intervals were significantly less. Changes in heart rate and PR, QT and QTc intervals were significantly negatively correlated with the value of the respective cardiac parameters at baseline. Changes in PR interval were significantly positively correlated with log desipramine, log 2-OH-DMI and log (desipramine + 2-OH-DMI). Stepwise multiple regression analyses showed that, for PR interval, each of the three plasma level variables showed a significant ability to improve R2 over that obtained from baseline PR alone. These findings suggest that both 2-OH-DMI and desipramine plasma levels predict a prolongation of intracardiac conduction in younger adults and that monitoring both levels may be useful in the clinical management of certain younger adult patients.

A combined group and individual approach to outpatient lithium treatment.

The authors describe a clinic they began in 1980 for patients who take lithium carbonate for the prophylaxis of recurrent psychiatric disorders. They discuss in detail what they have found to be the advantages of this approach. They recommend that other outpatient psychiatric facilities consider a similar program.

How are depression and bulimia related?

The idea that bulimia may be related to affective illness was encouraged by early reports of a high prevalence of clinical depression in bulimic patients as well as a high lifetime prevalence of depression in the families of these patients. More recent evidence suggests, however, that bulimia and major depression are distinct entities. The authors review clinical data, family studies, pharmacotherapy, and the neurobiology of bulimia and discuss the nature of the relationship between depression and bulimia.