Melanoma: Nieweg OE

van Everdingen JJ, van der Rhee HJ, Koning CC, Nieweg OE, Kruit WH, Coebergh JW, Ruiter DJ, Anonymous00197. · Kwaliteitsinstituut voor de Gezondheidszorg CBO, Postbus 20.064, 3502 LB Utrecht. · Ned Tijdschr Geneeskd. · Pubmed #16128181 No free full text.

Abstract: The guidelines 'Melanoma' (3rd revision) are evidence-based in nature. A number of outcomes are summarised in this article. Dermatoscopy deserves a standard role in the clinical diagnosis of pigmented skin abnormalities. Pathological findings from a diagnostic excision should be recorded meticulously to include anatomical localisation, type of intervention used, excision margin, diagnosis, Breslow thickness, and the completeness of the removal. The sentinel node procedure should be reserved for patients who want to be as informed as possible about their prognosis. The procedure is not considered a part of standard diagnosis. Sentinel node assessment should include stains for specific markers and should be conducted in multiple sections. The following margins of non-affected skin are recommended for therapeutic re-excision of melanoma: in situ melanoma, 0.5 cm; Breslow thickness < or = 2 mm, 1 cm; Breslow thickness > 2 mm, 2 cm. Pathological assessment of a re-excised specimen depends on the completeness of the first excision. Systematic adjuvant treatment of patients with melanoma is not recommended outside the context of a clinical study. Patients with metastatic melanoma are preferably treated within a clinical study. Outside of a clinical study, these patients should be treated with dacarbazine. There is no evidence to suggest that survival is improved by frequent follow-up. However, follow-up can be a useful way to meet the information needs of patients and care requirements for physicians.

Nieweg OE, van Rijk MC, Valdés Olmos RA, Hoefnagel CA. · No affiliation provided · Eur J Nucl Med Mol Imaging. · Pubmed #15875179 No free full text.

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Estourgie SH, Nieweg OE, Kroon BB. · No affiliation provided · Eur J Surg Oncol. · Pubmed #15296983 No free full text.

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Nieweg OE, Tanis PJ, de Vries JD, Kroon BB. · No affiliation provided · J Surg Oncol. · Pubmed #11745813 No free full text.

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Kroon BB, Noorda EM, Vrouenraets BC, van Slooten GW, Nieweg OE. · Department of Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam, the Netherlands. · Surg Oncol Clin N Am. · Pubmed #18722918 No free full text.

Abstract: Isolated limb perfusion with high-dose chemotherapy is an accepted treatment modality to achieve locoregional control in advanced melanoma of the extremities. The drug of choice is melphalan. Tumor necrosis factor-alpha is frequently added to melphalan in bulky disease, and this combination may be an option for repeat perfusion for recurrent melanoma after a first perfusion. Results of perfusions performed with tissue temperatures between 37 degrees C and 38 degrees C seem to be equivalent to those of the perfusions performed under mild hyperthermic conditions. Perfusion cannot be recommended as an adjunct to wide local excision in patients who have primary melanoma. Adjuvant perfusion in repeatedly recurrent limb melanoma, however, may be of value because it lengthens the limb recurrence-free interval and decreases the number of lesions per recurrence significantly. Regional toxicity of perfusion should be mild when risk factors are taken into account.

Tanis PJ, Nieweg OE, van den Brekel MW, Balm AJ. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Head Neck. · Pubmed #18213724 No free full text.

Abstract: The management of patients with clinically node-negative melanoma of the head and neck remains controversial. This is a systematic review of management strategies for stage I head and neck melanoma. Subgroup analysis of 1 randomized controlled trial (RCT) and most available cohort studies do not reveal a significant impact of elective neck dissection on survival. For 1.2- to 3.5-mm-thick melanoma at all anatomical sites, 1 RCT does not show an overall significant melanoma-specific survival benefit of sentinel node biopsy, but subgroup analysis suggests a survival benefit for lymph node-positive patients, confirming findings from 3 retrospective series. Sentinel node biopsy in the head and neck region can be technically demanding, with lower identification rates and higher false-negative rates. There is no conclusive survival advantage of either elective neck dissection or sentinel node biopsy in patients with clinically node-negative head and neck melanoma of intermediate thickness.

Noorda EM, Vrouenraets BC, Nieweg OE, Kroon BB. · Department of Surgery, Slotervaart Hospital, Louwesweg 6, Amsterdam 100 BK, the Netherlands. · Surg Oncol Clin N Am. · Pubmed #16632221 No free full text.

Abstract: Adjuvant perfusion to excision of a primary melanoma cannot be recommended because of its limited effect. In patients who have frequently recur-ring resectable locoregional melanoma, perfusion may provide valuable loco-regional disease control by decreasing the number of recurrences and lesions per recurrence. Randomized studies are needed to further establish the role of perfusion as an adjuvant treatment for resectable recurrences of melanoma. Unresectable limb melanoma is the primary indication for perfusion. Better response rates tend to be seen when TNF-a is used in patients who have a high tumor load. Repeat perfusion is feasible, resulting in response rates similar to those of a first perfusion for locoregional melanoma.Older age itself is not a contraindication for perfusion. The long-term health-related quality of life of survivors of melanoma who underwent treatment with perfusion is comparable to that of their healthy peers in the general Dutch population.

Nieweg OE, Kroon BB. · The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Surgery, Plesmanlaan 121, Amsterdam 1066 CX, the Netherlands. · Surg Oncol Clin N Am. · Pubmed #16632217 No free full text.

Abstract: This article critically evaluates the practice of follow-up for patients who have undergone treatment for a primary melanoma without evidence of metastases. One conclusion from this analysis is that the benefits of routine imaging and blood testing are insufficient to warrant a place in routine follow-up. Few patients who have metastases are identified in this fashion and even fewer survive because they underwent these tests. Far more often, false-positive results occur, which invariably cause unnecessary concern, lead to additional unnecessary testing, and may even result in needless surgery. Based on the evidence available, the relevance of follow-up per se must even be challenged. No convincing evidence exists that regional control, survival, and quality of life improve through surveillance. Other reasons for surveillance may be present, but these are less imperative. The present findings challenge current practice.

Gallegos-Hernández JF, Nieweg OE, Tanis PJ, Valdés-Olmos RA, Kroon BB. · División de Cirugía Hospital de Oncología CMN SXXI, IMSS, Av. Cuauhtémoc 330 Col. Doctores, CP 06725, México, D.F. · Gac Med Mex. · Pubmed #14635563 No free full text.

Abstract: The trend to implement sentinel node biopsy as standard of care in patients with clinically localized melanoma is encouraged by the following three factors: the technique of lymphatic mapping has matured to the point that consensus was reached on how the procedure should be carried out, surgeons showed that they can find the node in nearly 100% of patients, and tumor-status was shown to be the most powerful prognostic factor. However, recent studies revealed unfavorable new information that questions the wisdom of this trend. Three studies published in 2001 with a combined total of 1,851 patients show false-negative rates of 16-25%. Another unnerving finding is the 13-19% incidence of in-transit metastases in patients with a tumor-positive sentinel node, reported by three groups. The ultimate purpose of lymphatic mapping is to provide sentinel node positive patients with early therapeutic measures, such as regional node dissection and adjuvant systemic treatment. However, there is currently no evidence that this approach results in improved regional control and survival. Sentinel node biopsy can only become part of routine patient management if the tumor-status of the sentinel node carries clear implications of proven benefit for the manner in wich patients are managed and if regional control is not jeopardized.

Nieweg OE, Eggermont AM, Kroon BB. · Het Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, afd. Heelkunde, Plesmanlaan 121, 1066 CX Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #12369437 No free full text.

Abstract: Elective lymph node dissection is selectively performed in patients with clinically localised melanoma. Randomised studies suggest that survival is improved only in a few subgroups of patients, whereas all patients are exposed to the substantial risk of operative morbidity. Sentinel node biopsy enables the early detection of lymph node metastases from melanoma with less morbidity. The technique has been standardised. The sentinel node can be identified in almost 100% of the patients. The tumour status of the node is the most important prognostic factor in patients with clinically localised melanoma. This information is essential for studies of adjuvant systemic treatment. Regrettably, there is confusion about the definition of a sentinel node. In addition, the sensitivity of the sentinel node approach is unclear. Furthermore, it is uncertain whether early lymph node dissection improves regional control and survival. Sentinel node biopsy is not yet the standard of care.

Kroon BB, Noorda EM, Vrouenraets BC, Nieweg OE. · The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. · J Surg Oncol. · Pubmed #11920783 No free full text.

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Kroon BB, Nieweg OE. · Department of Surgery, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam. · Ann Chir Gynaecol. · Pubmed #11079795 No free full text.

Abstract: The following guidelines are recommended in the management of malignant melanoma. An excisional biopsy is the appropriate diagnostic procedure for a skin lesion suspected of being a melanoma. The advised margin for diagnostic excision is 2 mm of macroscopically normal skin around the lesion; the margins for therapeutic excision are 1 cm of normal skin for a lesion with a Breslow thickness of < 2 mm and 2 cm when the Breslow thickness is > 2 and < or = 4 mm. A margin of at least 2 cm also appears to be justified for thicker melanomas. Elective lymph node dissection is not recommended. Sentinel node biopsy appears to be a promising method to detect occult metastases in the regional lymph nodes. If regional lymph node metastases are present, therapeutic regional lymph node dissection must be conducted. Isolated regional perfusion is indicated for inoperable tumour growth in an extremity. Radiotherapy can be applied palliatively or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy is still experimental. There is no standard treatment for patients with haematogenic metastasis and they should be entered in trials whenever possible. A follow-up period of 5 years is sufficient for patients with a melanoma of < or = 1.5 mm Breslow thickness and of 10 years when the Breslow thickness is > 1.5 mm. The patients should be actively involved in the follow-up (inspection, palpation). Regular routine blood tests and radiological examinations are not considered to be worthwhile. There is no evidence that the growth of micro-metastases is stimulated by hormonal changes during pregnancy or contraceptive pill use. Excessive exposure to ultraviolet radiation should be discouraged.

Valdés Olmos RA, Hoefnagel CA, Nieweg OE, Jansen L, Rutgers EJ, Borger J, Horenblas S, Kroon BB. · Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands. · Eur J Nucl Med. · Pubmed #10199926 No free full text.

Abstract: The validation of the sentinel node concept in oncology has led to the rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping with intraoperative probe detection this nuclear medicine procedure is being increasingly used to identify and detect the sentinel node in melanoma, breast cancer, and in other malignancies such as penile cancer and vulvar cancer. In the past lymphoscintigraphy has been widely applied for various indications in oncology, and in the case of the internal mammary lymph-node chain its current use in breast cancer remains essential to adjust irradiation treatment to the individual findings of each patient. In another diagnostic area, lymphoscintigraphy is also useful to document altered drainage patterns after surgery and/or radiotherapy; its use in breast cancer patients with upper limb oedema after axillary lymph-node dissection or in melanoma patients with lower-extremity oedema after groin dissection can provide information for physiotherapy or reconstructive surgery. Finally, the renewed interest in lymphoscintigraphy in oncology has led not only to the rediscovery of findings from old literature reports, but also to a discussion about methodological aspects such as tracer characteristics, image acquisition or administration routes, as well as to discussion on the study of migration patterns of radiolabelled colloid particles in the context of cancer dissemination. All this makes the need for standardized guidelines for lymphoscintigraphy mandatory.

Luiten RM, Kueter EW, Mooi W, Gallee MP, Rankin EM, Gerritsen WR, Clift SM, Nooijen WJ, Weder P, van de Kasteele WF, Sein J, van den Berk PC, Nieweg OE, Berns AM, Spits H, de Gast GC. · Clinical Immunotherapy, Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. · J Clin Oncol. · Pubmed #16260696 No free full text.

Abstract: PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.

Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Wang HJ, Anonymous00289. · John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Ann Surg. · Pubmed #16135917 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. SUMMARY BACKGROUND DATA: Since our introduction of LM/SNB in 1990, this technique has been widely adopted and has become part of the American Joint Committee on Cancer (AJCC) staging system. Eleven years ago, the authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT-I) to compare 2 treatment approaches: wide excision (WE) plus LM/SNB with immediate complete lymphadenectomy (CLND) for sentinel node (SN) metastases, and WE plus postoperative observation with CLND delayed until the subsequent development of clinically evident nodal metastases. METHODS: After each center achieved 85% accuracy of SN identification during a 30-case learning phase, patients with primary cutaneous melanoma (> or =1 mm with Clark level > or =III, or any thickness with Clark level > or =IV) were randomly assigned in a 4:6 ratio to WE plus observation (WEO) with delayed CLND for nodal recurrence, or to WE plus LM/SNB with immediate CLND for SN metastasis. The accuracy of LM/SNB was determined by comparing the rates of SN identification and the incidence of SN metastases in the LM/SNB group versus the subsequent development of nodal metastases in the regional nodal basin of those patients with tumor-negative SNs. Early morbidity of LM/SNB was evaluated by comparing complication rates between the 2 treatment groups. Trial accrual was completed on March 31, 2002, after enrollment of 2001 patients. RESULTS: Initial SN identification rate was 95.3% overall: 99.3% for the groin, 95.3% for the axilla, and 84.5% for the neck basins. The rate of false-negative LM/SNB during the trial phase, as measured by nodal recurrence in a tumor-negative dissected SN basin, decreased with increasing case volume at each center: 10.3% for the first 25 cases versus 5.2% after 25 cases. There were no operative mortalities. The low (10.1%) complication rate after LM/SNB increased to 37.2% with the addition of CLND; CLND also increased the severity of complications. CONCLUSIONS: LM/SNB is a safe, low-morbidity procedure for staging the regional nodal basin in early melanoma. Even after a 30-case learning phase and 25 additional LM/SNB cases, the accuracy of LM/SNB continues to increase with a center's experience. LM/SNB should become standard care for staging the regional lymph nodes of patients with primary cutaneous melanoma.

Noorda EM, Vrouenraets BC, Nieweg OE, Klaase JM, van der Zee J, Kroon BB. · Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. · Melanoma Res. · Pubmed #12883366 No free full text.

Abstract: The aim of this study was to assess the results of an isolated limb perfusion (ILP) schedule with high dose hyperthermia (42-43 degrees C) and melphalan, applied sequentially in patients with advanced melanoma of the limbs. Seventeen patients with extensive recurrent or bulky melanoma of a limb were treated with hyperthermic femoral ILP (42-43 degrees C) without drugs followed by normothermic (37-38 degrees C) ILP with melphalan. Eleven patients (65%) had a complete response. Three patients (27%) had limb recurrences after 5, 6 and 18 months, respectively. The 5 year limb recurrence-free interval for patients with a complete response was 63%. Limb toxicity was mild; pressure-related blistering and transient sensory disturbances occurred after the hyperthermic ILP, and 88% of the patients had a grade II reaction (mild erythema and oedema) after the second ILP. This sequential ILP schedule resulted in a high complete response rate and a low limb-recurrence rate in patients with extensive, recurrent melanoma of the limbs at the cost of only mild toxicity. This regimen could be an alternative to ILP with tumour necrosis factor-alpha and melphalan.

Estourgie SH, Nieweg OE, Valdés Olmos RA, Hoefnagel CA, Kroon BB. · Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. · Ann Surg Oncol. · Pubmed #12839854 No free full text.

Abstract: BACKGROUND: The aim of this study was to evaluate the results of sentinel node biopsy in cutaneous melanoma at our institute. METHODS: A total of 250 patients with cutaneous melanoma were studied prospectively. Preoperative lymphoscintigraphy was performed after injection of (99m)Tc-nanocolloid intradermally around the primary tumor or biopsy site (.32 mL, 65.5 MBq [1.8 mCi]). The sentinel node was surgically identified with the aid of patent blue dye and a gamma ray detection probe. The median follow-up was 72 months. RESULTS: Lymphoscintigraphic visualization was 100%, and surgical identification was 99.6%. In 60 patients (24%), 1 or more sentinel nodes were tumor positive at initial pathology evaluation. Late complications after sentinel node biopsy of the remaining 190 patients were seen in 35 patients (18%). The false-negative rate was 9%. In-transit metastases were seen in 7% of sentinel node-negative and 23% of sentinel node-positive patients. The estimated 5-year overall survival rates were 89% and 64%, respectively (P <.001). CONCLUSIONS: This study confirms that the status of the sentinel node is a strong independent prognostic factor. The false-negative rate and the incidence of in-transit metastases in sentinel node-positive patients are high and have to be weighed against the possible survival benefit of early removal of nodal metastases.

Strobbe LJ, Jonk A, Hart AA, Peterse JL, Wobbes T, Nieweg OE, Kroon BB. · Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam. · Ann Surg Oncol. · Pubmed #11314936 No free full text.

Abstract: BACKGROUND: A selection of melanoma patients with groin metastases can benefit from a pelvic (iliac/obturator) lymph node dissection in addition to the infrainguinal dissection. However, there are no reliable criteria to determine which patients may benefit from such an inguinal-pelvic lymphadenectomy. METHODS: In 142 patients (group A) out of a review of 214 groin dissections performed between 1980 and 1994, the tumor status of Cloquet's node was traced retrospectively. In 52 additional patients (group B), the status of Cloquet's node was registered prospectively. The number of positive lymph nodes and the total numbers of retrieved nodes were recorded as well. All patients underwent a combined therapeutic inguinal-pelvic lymph node dissection between January 1995 and June 1999 in a tertiary referral center. RESULTS: Cloquet's node was free of disease in 18 of 39 patients with involved pelvic nodes in the retrospective study (sensitivity, 54%; negative predictive value, 83%). In the prospective study, 9 of the 20 patients with involved pelvic nodes had a tumor-free Cloquet's node (sensitivity, 55%; negative predictive value, 78%). Additional immunohistochemical staining of Cloquet's node resulted in a sensitivity of 65%. In the combined group A&B, the number of positive nodes in the inguinal region (cutoff point more than three nodes) had a sensitivity of 41% and a negative predictive value of 78% to determine the pelvic nodal status. When we combined the number of positive inguinal nodes and Cloquet's node in group A&B, the best sensitivity was 56% and the best negative predictive value was 82%. CONCLUSIONS: Cloquet's node has a low sensitivity to predict the pelvic nodal tumor status. This was barely improved when we accounted for the number of positive inguinal nodes. Groin lymph node dissections should encompass the iliac and obturator compartments in patients with palpable inguinal node metastases.

Jansen L, Koops HS, Nieweg OE, Doting MH, Kapteijn BA, Balm AJ, Vermey A, Plukker JT, Hoefnagel CA, Piers DA, Kroon BB. · Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. · Head Neck. · Pubmed #10585602 No free full text.

Abstract: BACKGROUND: Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region. METHODS: Thirty consecutive patients with clinically localized cutaneous melanoma in the head and neck region were included. Sentinel node biopsy was performed with blue dye and a gamma probe after preoperative lymphoscintigraphy. Average follow-up was 23 months (range, 1-48). RESULTS: In 27 of 30 patients, a sentinel node was identified (90%). Only 53% of sentinel nodes were both blue and radioactive. A sentinel node was tumor-positive in 8 patients. The sentinel node was false-negative in two cases. Sensitivity of the procedure was 80% (8 of 10). CONCLUSIONS: Sentinel node biopsy in the head and neck region is a technically demanding procedure. Although it may help determine whether a neck dissection is necessary in certain patients, further investigation is required before this technique can be recommended for the standard management of cutaneous head and neck melanoma.

Vrouenraets BC, in't Veld GJ, Nieweg OE, van Slooten GW, van Dongen JA, Kroon BB. · Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek ziekenhuis), Amsterdam, The Netherlands. · Eur J Surg Oncol. · Pubmed #10529261 No free full text.

Abstract: AIMS: To assess long-term functional morbidity in patients entered in the prospective randomized EORTC trial investigating the role of adjuvant isolated limb perfusion (ILP) with melphalan for high-risk primary melanoma. METHODS: In 65 patients (ILP 36, wide excision only 29), limb circumference and joint mobility measurements were performed on the treated and the contralateral limb after a mean interval of 48 months after primary treatment. The two treatment groups were comparable regarding age, sex distribution, percentage of skin grafts or regional lymph-node dissections, and interval between primary treatment and physical measurements. RESULTS: None of the patients had severe complaints of the treated limb at the time of analysis. The ankle suffered most from ILP, with a statistical significant restricted extension in approximately 40% of the perfused patients. Abduction of the shoulder was minimally affected in treated upper limbs, probably as a result from the formation of scar tissue after axillary lymph-node dissection. Although no significant differences could be demonstrated in the circumference of upper or lower limbs, atrophy was seen in 24% of perfused lower limbs. Of the five perfused patients who developed oedema, four had also undergone a regional lymph-node dissection. CONCLUSION: This risk of long-term functional morbidity should be weighed against the possible advantages of ILP in patients with limb melanoma or sarcoma.

Morton DL, Thompson JF, Essner R, Elashoff R, Stern SL, Nieweg OE, Roses DF, Karakousis CP, Mozzillo N, Reintgen D, Wang HJ, Glass EC, Cochran AJ. · John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Ann Surg. · Pubmed #10522715 links to  free full text

Abstract: 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.

Vrouenraets BC, Kroon BB, Ogilvie AC, van Geel AN, Nieweg OE, Swaak AJ, Eggermont AM. · Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek ziekenhuis), Amsterdam. · Ann Surg Oncol. · Pubmed #10379864 No free full text.

Abstract: BACKGROUND: Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation. METHODS: Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes. RESULTS: Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients. CONCLUSIONS: Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.

van der Ploeg IM, Kroon BB, Antonini N, Valdés Olmos RA, Nieweg OE. · Departments of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. · Ann Surg. · Pubmed #19474678 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to evaluate the micromorphometric Starz-classification in melanoma patients. SUMMARY BACKGROUND DATA: The micromorphometric Starz-classification suggests that melanoma patients with a sentinel node metastasis invading no more than 0.3 mm (S-I) or 0.31 to 1.0 mm (S-II) below the capsular level can be spared further surgery, while invasion of the metastasis of more than 1.0 mm (S-III) implies a need for completion dissection. METHODS: Seventy patients with sentinel node metastases were studied. Twenty patients with an S-I or S-II classification were spared further surgery and 50 S-III patients underwent completion dissection. The median follow-up time was 33 months. RESULTS: No lymph node recurrences were detected in the 20 S-I, II patients. Six of the 50 S-III patients (12%) had additional involved nodes in the dissection specimen. In these patients no recurrences developed in the cleared regional basins. Overall 3-year survival was 100% in the S-I, II patients and 80% in the S-III patients (P = 0.04). Three-year disease-free survival rates were 83% and 60%, respectively (P = 0.40). CONCLUSIONS:: This study suggests that further surgery is unnecessary in S-I and S-II patients, while it does seem prudent to carry out completion dissection in S-III patients. The distinct survival difference between the 2 groups of patients suggests that the S-classification also has prognostic implications.

Balch CM, Morton DL, Gershenwald JE, McMasters KM, Nieweg OE, Powell B, Ross MI, Sondak VK, Thompson JF. · Departments of Surgery, Oncology, and Dermatology, Johns Hopkins Medical Center, Baltimore, Maryland, USA. · J Am Acad Dermatol. · Pubmed #19389531 No free full text.

Abstract: An international panel was convened by the organizing committee of the International Sentinel Node (SN) Society (ISNS) at their meeting in Sydney, Australia, on February 21, 2008, to address questions about SN biopsy (SNB) for melanoma. The panelists subsequently wrote this consensus statement, based on their interpretation of current evidence, as a guide to clinical treatment of patients with clinically localized melanoma. The panel comprised a cross section of expert melanoma surgeons who have contributed data and leadership to investigations of SNB.

van der Ploeg IM, Valdés Olmos RA, Kroon BB, Wouters MW, van den Brekel MW, Vogel WV, Hoefnagel CA, Nieweg OE. · Department of Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. · Ann Surg Oncol. · Pubmed #19184226 No free full text.

Abstract: BACKGROUND: The hybrid single-photon emission computed tomography camera with integrated CT (SPECT/CT) fuses tomographic lymphoscintigrams with anatomical CT data. SPECT/CT shows the exact anatomical location of a sentinel node and may detect additional drainage. The purpose of this study was to explore its potential in patients with melanoma. METHODS: We studied 85 patients with melanoma with conventional lymphoscintigrams that were difficult to interpret (51 patients), that showed an unusual drainage pattern (33 patients), or with nonvisualization (1 patient). Forty-one patients had melanoma on an extremity, 31 on the trunk, and 14 in the head and neck region. SPECT/CT was performed following late conventional imaging without reinjection of the radiopharmaceutical. RESULTS: Conventional imaging suggested 214 sentinel nodes in 84 of the 85 patients (99%). SPECT/CT showed these same nodes and 12 extra sentinel nodes in seven patients (8%). Ten of these additional nodes were harvested, of which three nodes of two patients harbored metastases. There was a clear advantage of SPECT/CT in 30 patients (35%), resulting in a different incision in 17 patients, an incision at another site in 8, and an extra incision in 5 patients. The value was questionable in 19 patients (22%) in whom sentinel nodes were more clearly visualized by SPECT/CT, although the incision remained unchanged. There was no additional value of SPECT/CT in 36 patients (42%). CONCLUSIONS: SPECT/CT detects additional drainage and shows the exact anatomical location of sentinel nodes in patients with inconclusive conventional lymphoscintigrams. SPECT/CT facilitates surgical exploration in difficult cases and may improve staging.