Hospital doctors, general practitioners and dentists learning together

BACKGROUND: Recurrent melanoma of the extremity has been treated by local excision, systemic chemotherapy, amputation, or a combination of these approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb preservation through isolation, allowing the administration of chemotherapy in higher doses than is possible through systemic treatment. METHODS: An experimental group of 59 HILP patients with melanoma recurrences of the extremity was studied prospectively. A control group of 248 melanoma patients with similar recurrences was excluded from HILP because their recurrences were in non-extremity locations. The experimental group underwent HILP and excision; the control group had excision only. The experimental procedure consisted of vascular isolation of the affected extremity and a 1-hour perfusion with melphalan. Temperatures were maintained at 40 degrees C in the perfusion circuit. RESULTS: The HILP patients had a lower rate of locoregional recurrence (P=.028) and demonstrated increased survival (P=.026) compared to the control group. In multivariate regression analysis, which included age, ulceration and thickness of the primary, and the treatment variable of perfusion, age (P=.02) and perfusion for the treatment of recurrence (P=.006) were significant predictors of survival. CONCLUSIONS: HILP improves prognosis by sterilizing the treated extremity, controlling locoregional disease, and perhaps preventing metastasis, thus having a positive impact on overall survival.     

The current surgical treatment of primary malignant melanoma of the skin

In our Department, between 1991 and 1996, 132 patients, there of 87 male-45 female, average age of 48.2 years underwent surgery because of stage 1 (T2) to stage 3 melanoma that was located on the skin. None of patients suffered from early or in situ melanoma. Our retrospective study was based on those 94 patients who had been followed up by Department or dermatology-oncology in our medical centre. Surgery is still the primary treatment for cutaneous malignant melanoma. Thin melanomas (up to 2 mm in thickness) can be excised with 2 cm margins. Whether this is also true for thicker melanomas is not known and the only way to obtain more knowledge is to participate in prospective randomised studies. Elective lymph node dissection is associated with significant morbidity which includes lymphedema, wound complications and paresthesias of the extremity. For this reason we use an alternative operative approach uses selective lymphadenectomy with identification of the sentinel node.     

A cytotoxic pennogenin glycoside from Majanthemum dilatatum

Axillary dissection is the major cause of morbidity in breast cancer and primary cutaneous melanoma of the extremity. In the present study, we examine the potential benefits and advantages of endoscopic axillary lymph node dissection over conventional surgery. Twenty endoscopic axillary dissections and 10 lymph node samplings were performed in 10 cadavers (four male, six female). A preperitoneal distention balloon (PDB) system was used to dissect the axilla. In four of the cadavers, the procedure was followed by open surgery. The axillary contents were examined for lymphatic tissue by a pathologist. The endoscopic technique offered easy access to the axilla and clear visualization of the axillary vein, as well as the long thoracic and thoracodorsal nerves. Results were comparable to those achieved with the classic surgical dissection. Endoscopy is feasible for axillary lymph node dissection and sampling in cases of breast cancer and primary cutaneous melanoma of the extremity. Further studies in patients are needed to reach definitive conclusions.     

Isolated hyperthermia chemotherapy perfusion for limb melanoma

Safe techniques for regional chemotherapy of the limbs by perfusion are now available. The method is effective in obtaining regionally confined high levels of toxic drugs or chemotherapeutic agents in the isolated areas. The best responses have been observed in limb melanoma with recurrent or intransit disease. Chemotherapy by perfusion as an adjunct to surgical excision reduces the local recurrence and the regional and lymph node metastases. Our survivals for adjunctive perfusion for Stage I melanomas with Level V and lesions 5 mm thick and thicker are better than usually reported. Regional chemotherapy has had an important role in reduction of major amputations for the control of limb melanoma. Multiple chemotherapeutic limb perfusions can further extent survival in patients with recurring melanoma.     

Ilioinguinal block dissection for malignant melanoma

A retrospective analysis of 41 patients treated for metastatic inguinal lymph node malignant melanoma is presented: 16 underwent inguinal node excision and 25 ilioinguinal node excision. The two groups were well matched for age, sex and other characteristics. The mean time in hospital (inguinal 20 days, ilioinguinal 18 days) and the complication rates (inguinal, ten of 16 patients, ilioinguinal, 13 of 25) were similar in each group. The incidence of groin relapse, defined as the development of symptomatic melanoma in the region of the inguinal or iliac node basins following block dissection, was lower after ilioinguinal block dissection (inguinal, three patients; ilioinguinal, none). Histological examination demonstrated a high proportion of iliac node involvement (13 of 25 patients), even in those with a single mobile inguinal lymph node clinically and no clinical or computed tomographic evidence of iliac node involvement. This supports the value of ilioinguinal block dissection and suggests that the associated morbidity need not be greater than that associated with inguinal clearance alone.     

Management of cutaneous melanoma M0: state of the art and trends

This article reviews the epidemiology, diagnosis and treatment of cutaneous melanoma, including the most recent developments. The combination of positive family history, fair complexion, number of nevi, exposure to sun and/or chromosomal alterations seem to be implicated in the pathogenesis of cutaneous melanoma. Melanomas can be classified according to their growth patterns, and tumour microstaging is of straightforward predictive value for survival and risk of metastasis, although new factors are also being investigated. As yet, surgical excision is the only effective treatment available for primary tumours, resection margins varying according to tumour thickness. Elective node dissection is, however, no longer advocated for melanomas thinner than 1.5 mm, and there is disagreement as to its role for thicker lesions. In contrast, selective node dissection at the time of definitive surgery is becoming more widely accepted, with regional node dissection being restricted to positive cases. Therapeutic dissection is required for lymph node involvement, the most common pattern of recurrence from melanoma, which affects nearly 30% of all patients. Complete remission rates from isolated limb perfusion, which has been employed in patients with multiple recurrences or in-transit metastases, range from 40 to 90%, depending on drugs and techniques used in different series; the best responses so far have been obtained with tumour necrosis factor in combination with melphalan. Patients with thick lesions (> 4 mm) or lymph node metastases have a high risk of micrometastases that would warrant adjuvant therapy. The only agent found to affect survival is interferon alpha-2.     

Lymphatic mapping and selective lymphadenectomy as an alternative to elective lymph node dissection in patients with malignant melanoma

This article reviews the use of selective lymphadenectomy, otherwise known as sentinel lymph node biopsy, as a clinical alternative in patients with malignant melanoma. This represents a compromise between the two traditional treatment modalities, elective lymph node dissection or observation of the regional nodal basin followed by therapeutic lymph node dissection once disease becomes clinically apparent.     

Outpatient pelvic lymph node dissection

PURPOSE: Staging pelvic lymph node dissection is an important part of the evaluation of most patients with prostatic carcinoma. While laparoscopic pelvic lymph node dissection provides an alternative to standard pelvic lymph node dissection, it has been associated with a significant learning curve, high major complication rate, frequent hospitalization and greater expense. We sought to modify the technique of pelvic lymph node dissection to allow its performance as an outpatient procedure. MATERIALS AND METHODS: Pelvic lymph node dissection was performed through bilateral 3 cm. incisions overlying the obturator fossa in 11 patients. RESULTS: Nodes sampled ranged from 5 to 26 per patient that differed insignificantly from those undergoing standard pelvic lymph node dissection. Four patients had lymph node metastases. Nine procedures were performed entirely on an outpatient basis. One complication (external vein injury) was repaired with a single suture after extending the incision to 6 cm. CONCLUSIONS: Outpatient pelvic lymph node dissection through small incisions provides an attractive alternative to standard or laparoscopic lymph node dissection. With further experience it may become the procedure of choice for staging prostatic carcinoma in patients with a high risk of pelvic lymph node metastases.     

Gastric carcinoma resected 95 months after being diagnosed: report of a case

It is usually assumed that patients with gastric carcinoma will almost certainly die within 5 years if they do not receive treatment. We report herein a rare case of curative gastrectomy being performed 95 months after gastric carcinoma was diagnosed. A 37-year-old Japanese man had an upper gastrointestinal endoscopy with biopsy which revealed moderately differentiated adenocarcinoma of the stomach. This was diagnosed as type IIc early gastric carcinoma with ulceration but he refused surgery. At 45 years of age, 95 months later, he presented to our hospital with melena, at which time lesions in an identical location had enlarged to Borrmann type 3 advanced gastric carcinoma. Thus, a total gastrectomy with regional lymph node dissection was performed. Although there was no liver or peritoneal metastasis, the regional lymph nodes were involved; however, the patient recovered well and is still alive without any further recurrence roughly 4 years postoperatively. The natural history of gastric carcinoma and the malignant cycle are discussed following the presentation of this case.     

Pelvic exenteration for malignant melanomas of the vagina or urethra with over 3 mm of invasion

Pelvic exenteration has usually been employed as salvage treatment for gynecologic malignancies which have failed primary radiotherapy. The therapeutic mainstay for vulvar melanomas has become wide local excision with or without concurrent regional node dissection. Patients with primary melanoma of the vagina who undergo exenteration as primary therapy may experience 50% 5-year survival if the pelvic nodes are free of metastases. However, the overall 5-year survival for vaginal melanoma is 15%. In our patient population, there have been four patients with vaginal or urethral melanomas treated primarily with pelvic exenteration. The purpose of this study was to report that patients with vaginal or urethral melanomas over 3 mm in thickness may benefit from primary pelvic exenteration. Four patients underwent pelvic exenteration at Indiana University Medical Center for malignant melanoma of the vagina or urethra between 1986 and 1992. The pathologic specimens of all patients were analyzed for thickness, growth pattern, and nodal metastases. Patient age ranged from 50 to 71. Thickness of the melanomas ranged from > 3 to 12 mm. All four patients underwent exenterations, three total and one anterior. All patients had negative pelvic and inguinal nodes at the time of surgery. None of the patients has experienced a recurrence. Three of four patients are alive without evidence of disease at 31 to 97 months following their exenteration. One patient died postoperatively of cardiopulmonary complications. Patients with melanomas of the vagina and female urethra, greater than 3 mm in thickness, may benefit from primary pelvic exenteration.     

Isolated hyperthermic limb perfusion with melphalan and tumor necrosis factor in malignant melanoma

OBJECTIVE: To analyse a personal series of cases of malignant melanoma of a limb with regional metastasis treated by isolated cytostatic perfusion of both recombinant human tumour necrosis factor (rhTNF-alpha) and melphalan, reported to produce a response rate of up to 100%. PATIENTS AND METHODS: 23 isolated hyperthermic regional perfusions were performed between 1993 and 1995 in 21 patients (17 women, four men) with proven regionally metastatic malignant melanoma of the limb, using rhTNF-alpha and melphalan in combination. Perfusion time was 90 min, at a tissue temperature of 38 degrees to 40 degrees C and a perfusion pressure 10-15 mm Hg below mean arterial. RESULTS: All systemic effects of the limb perfusions were easily manageable under intensive care monitoring. There were no severe disturbances (WHO grade 3/4) of cardiovascular or pulmonary functions. One patient, who had sustained a marked leak during the perfusion, died two days after the perfusion of severe pneumonia and pulmonary emboli from a femoral vein thrombosis. Two further perfusions were terminated because of a leakage rate of more than 10%. A rise in bilirubin and the transaminases occurred in 11 of the 23 perfusions up to WHO grade 2 (n = 9) and 3 (n = 2). Renal functions were temporarily impaired in three of the 21 patients (WHO grade 1). Complete tumour regression was obtained in 13 patients, a partial one in three (response rate 80%). After a median follow-up period of 15 months five of the 13 patients developed a regional recurrence. CONCLUSION: The observed response rate is higher than that with melphalan alone as reported in the literature. To clarify this difference a randomized phase III study comparing the two methods has been initiated.     

Long-term follow-up of positive cultures in 500 abdominal aortic aneurysms

The surgical management of regional nodes in patients with cancer has been controversial for many years. This paper reviews the role of elective lymph node dissection in the management of malignant melanoma. The evidence for and against elective lymphadenectomy is discussed and a policy of therapeutic, rather than elective, lymph node excision recommended.     

Complications of axillary lymph node dissection for carcinoma of the breast: a report based on a patient survey

BACKGROUND: Axillary lymph node dissection is commonly performed as part of the primary management of breast carcinoma. Its value in patient management, however, has recently been questioned. Few studies exist that document long term complications. METHODS: Four hundred thirty-two patients with Stage I or II breast carcinoma who were free of recurrence 2-5 years after surgery were identified. A cross-sectional survey was conducted to determine the prevalence of long term symptoms and complications as perceived by the patient, and patient and treatment factors that may have predicted complications were determined. Three hundred thirty of the 432 (76%) completed a mailed, self-administered questionnaire. In addition, the medical records of the 330 patients were reviewed. Patient and treatment factors were analyzed with logistic regression. RESULTS: Numbness was reported by 35% of patients at the time of the survey. Pain was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%. Eight percent reported episodes of infection or inflammation at some point since the diagnosis of breast carcinoma. The majority of symptoms were mild and interfered minimally with daily activities. Younger age (P=0.001) was associated with more frequent reporting of pain. Numbness was more common in younger patients (P=0.004) as well as in those with a history of smoking (P=0.012). There was a positive association of limitation of arm motion with adjuvant tamoxifen therapy (P=0.016). Arm swelling was associated with both younger age (P=0.004) and greater body surface area (P=0.008). Radiation therapy was associated with a higher frequency of infection or inflammation in the arm and/or breast (P=0.001). CONCLUSIONS: Mild symptoms, especially pain and numbness, are common 2-5 years after axillary lymph node dissection. The frequency of inflammation or infection in patients treated with radiation to the breast or chest wall after an axillary lymph node dissection may be greater than previously appreciated. Severe complications or symptoms that have a major impact on daily activities are uncommon. These findings should help health care providers and their patients with breast carcinoma weigh the pros and cons of axillary lymph node dissection.     

2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep]

The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.     

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group

PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.     

Isolated limb perfusion of an irradiated foot with tumor necrosis factor, interferon, and melphalan

A 57-year-old woman presented with the second recurrence of a high-grade malignant fibrous histiocytoma of the right foot, following previous local resection plus curative adjuvant radiotherapy. The first recurrence of the lesion was treated by isolated limb perfusion with cisplatin; the second recurrence was treated by isolated limb perfusion with tumor necrosis factor, interferon, and melphalan. The tumor and the area that had been irradiated showed a bluish color a few hours after tumor necrosis factor perfusion. Amputation of the right foot and leg below the knee had to be performed because of severe necrosis.     

Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases

PURPOSE: To determine whether treatment with an autologous whole-cell vaccine modified with the hapten dinitrophenyl (DNP vaccine) is an effective postsurgical adjuvant treatment for melanoma patients with clinically evident nodal metastases. PATIENTS AND METHODS: Eligible patients had regional nodal metastases that were large enough (> or = 3 cm diameter) to prepare vaccine. Following standard lymphadenectomy, patients were treated with DNP vaccine on a monthly or weekly schedule. RESULTS: Of 62 patients with metastasis in a single lymph node bed (stage III), 36 are alive after a median follow-up time of 55 months (range, 29 to 76); the projected 5-year relapse-free and overall survival rates are 45% and 58%, respectively. Of 15 patients with metastases in two nodal sites, five are alive with a median follow-up time of 73 months. An unexpected finding was the significantly better survival of older patients; the projected 5-year survival of patients greater than 50 versus < or = 50 years was 71% and 47%, respectively (P = .011, log-rank test). The development of a positive delayed-type hypersensitivity (DTH) response to unmodified autologous melanoma cells was associated with significantly longer 5-year survival (71% v 49%; P = .031). Finally, the median survival time from date of first recurrence was significantly longer for patients whose subcutaneous recurrence exhibited an inflammatory response (> 19.4 v 5.9 months; P < .001). CONCLUSION: Postsurgical adjuvant therapy with autologous DNP-modified vaccine appears to produce survival rates that are markedly higher than have been reported with surgery alone. Moreover, this approach has some intriguing immunobiologic features that might provide insights into the human tumor-host relationship.