Implications of Hyperthermic Intraperitoneal Chemotherapy Perfusion-Related Hyperglycemia.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) administration can be associated with hyperglycemia during perfusion. Little is known about this effect, and no previous studies have examined patient characteristics associated with perfusion-related hyperglycemia. METHODS: We retrospectively identified consecutive patients at a single institution treated with HIPEC from 8/2003 to 10/2016 who had intraoperative blood glucose measured. Hypertonic 1.5% dextrose-containing peritoneal dialysate was used as carrier solution in all patients. Comparisons were made using parametric [Student's t test, analysis of variance (ANOVA)], and nonparametric tests (χ 2, Kruskal-Wallis) where appropriate. RESULTS: There were 85 patients identified, with average age of 53 ± 12 years, 69 (81%) with appendiceal or colorectal peritoneal cancer. Most patients were perfused with mitomycin C (69%) or oxaliplatin (24%). Intraoperative hyperglycemia (> 180 mg/dL) affected the majority of patients (86%), with values up to 651 mg/dL. Insulin was required for treatment in 66% of patients. Peak hyperglycemia occurred within an hour of perfusion in 91%, and resolved by postoperative day one in 91% of patients. Glucose > 309 mg/dL (highest quartile) was associated with longer operating time (p = 0.03) and with use of oxaliplatin compared with mitomycin C (p = 0.01). No association was found with other comorbidities, peritoneal carcinomatosis index score, or postoperative outcomes. CONCLUSIONS: Most patients experience hyperglycemia during HIPEC. This is not clearly associated with patient factors, and may be due to use of dextrose-containing carrier solution. Since perioperative hyperglycemia has potential negative impact, use of dextrose-containing carrier solution should be questioned and is worth investigating further.

Implications of Sentinel Lymph Node Drainage to Multiple Basins in Head and Neck Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for head and neck melanoma is challenging due to unpredictable drainage. We sought to determine the frequency of drainage to multiple lymphatic basins and asked if this was associated with prognosis in a large, single-center cohort. METHODS: We queried patients diagnosed with head and neck melanomas who had a SLNB performed from January 1998 to April 2016. Demographic and clinical characteristics were compared using Student's t test, Pearson chi-square analysis, log-rank test, Wilcoxon-Mann-Whitney test, and Kaplan-Meier curves. RESULTS: We identified 269 patients with head and neck melanoma that had SLNBs performed in the following locations: 223 neck, 92 parotid/preauricular, 29 occipital/posterior auricular, 1 axilla. There were 68 (25%) patients who had drainage to multiple basins. These patients were similar to those with single basin drainage in age, gender distribution, Breslow depth, and percent with a positive SLNB (all p > 0.05). Fewer patients with drainage to multiple basins had a completion lymph node dissection (CLND, p = 0.03). A trend toward increased 3-year locoregional recurrence was seen for patients with drainage to multiple basins in univariate analysis (27% vs. 18%, p = 0.10) but was lost in multivariate analysis (p = 0.49), possibly because of higher recurrence rates in patients with positive nodes but no CLND (p = 0.02). No difference was detected for distant recurrence or overall survival based on SLN drainage. CONCLUSIONS: Head and neck melanoma SLNB drainage to multiple basins is common. Drainage to multiple basins does not seem to be associated with increased sentinel lymph node positivity, locoregional recurrence, distant recurrence, or survival.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Fertility preservation in a patient with benign multicystic peritoneal mesothelioma.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor. Surgery is the only effective treatment for BMPM, and affected tissues occasionally must be sacrificed to achieve adequate debulking. A 25-year-old female was diagnosed with BMPM. She was counseled on fertility preservation and had oocyte cryopreservation prior to her debulking. Fertility preservation through embryo or oocyte cryopreservation is a valuable option for patients at risk of losing reproductive tissues during extensive surgery and chemotherapy.

Sequential radiofrequency ablation and surgical debulking for unresectable colorectal carcinoma: thermo-surgical ablation.

BACKGROUND AND OBJECTIVES: Despite decreasing frequency, local recurrences of unresectable colorectal cancer (CRC) remain difficult problems. These patients have few treatment options with conventional therapy. Preliminary results of sequential radiofrequency ablation (RFA) and surgical debulking (thermo-surgical ablation) suggest this technique may have benefit. METHODS: We reviewed a prospective database of patients undergoing thermo-surgical ablation for unresectable colorectal carcinoma from 2003 to 2011. RESULTS: Sixteen patients were treated with unresectable, recurrent abdomino-pelvic colorectal carcinoma: 11 in pelvis; 4 with isolated aortic/retroperitoneal disease; and 1 with pelvic and peri-adrenal/retroperitoneal disease. Eleven patients had recurrent rectal cancer and five had recurrent colon cancer. Median overall and 3-year actuarial survivals were 15 months and 24%, respectively. Median and 3-year PFS was 12 months and 19%, respectively. Three patients without disease have survived 0.75, 4.0, and 7.0 years. Two patients died at 5.0 and 5.5 years. A disease-free interval (DFI) of >24 months after initial resection was associated with longer overall survival (60 months vs. 4 months; P = 0.001). CONCLUSIONS: Thermo-surgical debulking appears to have a role in the treatment of some patients with recurrent, unresectable CRC; those patients with DFI >24 months after initial surgery benefited the most.

Combined thermal-surgical ablation of locally advanced abdominopelvic malignancies.

BACKGROUND: Treatment options for patients with inoperable primary or recurrent/metastatic abdominopelvic malignancies are limited, and these patients have short lifespan. The purpose of our study is to examine outcomes of combined open radiofrequency ablation (RFA) and surgical debulking of otherwise unresectable tumors. METHODS: Consecutive 50 patients were identified from an Institutional Review Board (IRB)-approved database undergoing ablation for unresectable abdominopelvic malignancies via conventional surgical methods in a single institution between 07/2003 and 09/2009. Patients were selected for debulking if they had a dominant mass that caused significant symptoms. RESULTS: Sixteen patients had primary tumors, and 34 presented with a recurrent/metastatic malignancy. The primary tumors were abdominopelvic sarcomas (eight patients), large desmoids (two), colorectal cancer (CRC) (two), and gastric cancer, mucinous cystic pancreatic neoplasm, gastrointestinal stromal tumor (GIST), and carcinoid (one each). The recurrent/metastatic tumors were CRCs (16 patients), abdominopelvic sarcomas (12), and GIST, prostate cancer, bladder cancer, melanoma, adrenal cancer, and pseudomyxoma peritonei recurrences (1 each). Twenty-two patients were alive and 28 died as of September 2009. Median survival for patients who died was 9.5 months and for patients who were alive was 22 months. Patients with primary tumors had 5-year survival of 18% compared with no survivors at 5 years in the recurrent/metastatic group (P = 0.002). CONCLUSIONS: Thermosurgical ablation of otherwise unresectable primary tumors and recurrent/metastatic abdominopelvic malignancies is feasible in selected cases. Patients with ablated primary tumors have a survival advantage over patients who have ablation for recurrent/metastatic disease.

Endoscopic-assisted closure of persistent gastrocutaneous fistula with a porcine fistula plug: report of a new technique.

Persistent gastrocutaneous (GC) fistula is a rare but problematic complication of gastrostomy feeding tube removal. Several techniques for nonoperative fistula closure have been attempted with mixed results. None has proven both satisfactorily simple and consistently effective. The authors present a case of persistent GC fistula treated by a simple outpatient endoscopic-assisted procedure using a porcine anal fistula plug. The procedure requires only basic endoscopic skills, similar to percutaneous gastrostomy tube placement, and it involves minimal operative time and risk to the patient. This technique offers a potential solution to the troublesome problem of persistent GC fistula.

Association of sentinel lymph node diameter with melanoma metastasis.

BACKGROUND: Lymph nodes are an important part of the immune system and the size of the lymph node reflects local immunologic activity. The purpose of this study was to examine the association between sentinel lymph node (SLN) size and the presence of nodal metastasis in patients with melanoma. METHODS: Retrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The maximum pathologic diameter and the volume of the largest node was used. A nodal diameter of 1.5 cm, included in 2 interquartile ranges of both positive and negative SLNs, was used as the cutoff for multivariate regression. RESULTS: Of 1,017 SLN biopsies, 826 (81%) had complete size measurements and were included in the analysis. Patients with a positive SLN were younger (median 50 vs 53 years, P = .032), had deeper primary lesions (2 vs 1.4 mm, P < .001), and had larger SLN volume (.8 vs .6 cc, P = .009) or maximum diameter (1.9 vs. 1.6 cm, P = .03). Sex, pathologic ulceration, mitosis, and the type or location of the primary was not statistically different. On multivariate analysis; age, depth of primary, and both SLN volume and maximum diameter remained significant. An SLN greater than 1.5 cm in maximum diameter has a 60% increased odds ratio of being positive after adjusting for age, sex, and depth of primary lesion (P = .046). CONCLUSIONS: Larger SLN maximum diameter is associated with nodal positivity independent of age, sex, depth of primary lesion, and location of SLN biopsy. The etiology and significance of larger SLNs warrant further analysis.

Analysis of melanoma recurrence following a negative sentinel lymph node biopsy.

Little attention has been paid to the characteristics and outcomes of patients who experience distant, local or regional recurrence of melanoma following a negative sentinel lymph node biopsy. This article aims to review the published literature on the topic and presents some general summaries regarding this patient population. Patients who experience a disease recurrence following a negative sentinel lymph node biopsy have a worse overall survival compared with patients with a positive sentinel lymph node biopsy. The implications and possible explanations for these findings are discussed in order to both underscore the need for in-depth investigation of local, regional or distant melanoma recurrence among patients following a true negative sentinel lymph node biopsy, as well as increased efforts to minimize the rate of false negative sentinel lymph node biopsies.

Transsacral exenteration of fixed primary and recurrent anorectal cancer.

BACKGROUND: Posteriorly fixed anorectal cancer is often considered incurable, but may be resectable using transsacral approaches. METHODS: We reviewed 45 patients undergoing transsacral exenteration for this problem since 1983 to determine outcome of such surgery. RESULTS: The group consisted of 38 men and 7 women; 17 had primary tumors, 28 had recurrent cancer: local excision, 1; low anterior resection, 11; or abdominoperineal resection, 16. Thirty-nine had prior XRT. Operative mortality was 4%. Severe pain was relieved in 16 of 22 (72%) patients. Crude recurrence rates are local 22%, local plus distant 11%, distant 16%. Five-year disease-free survival is 31% for primary disease, 32% for recurrence. Median survival is abdominoperineal resection recurrence, 24 months; primary cancer, 30 months; low anterior resection recurrence, 37 months. CONCLUSIONS: Transsacral exenteration relieved pain in 70% of patients with fixed anorectal cancer, and led to long-term survival in 31% to 32%. Prognosis trended toward benefit for recurrence after low anterior resection.

Smaller pelvic volume is associated with postoperative infection after pelvic salvage surgery for recurrent malignancy.

BACKGROUND: Patients with recurrent pelvic malignancy have few treatment options, and surgery is fraught with complications. We sought to characterize the relationship between radiographic pelvic volume and postoperative complications after pelvic salvage surgery. METHODS: A retrospective chart review of all patients undergoing pelvic exenteration or abdominoperineal resection for recurrent malignancy between 1998 and 2013 was performed. Preoperative computed tomography was used to determine pelvic volume. RESULTS: Forty-two patients underwent surgery for recurrent rectal (26, 62%), prostate (8, 19%), or anal squamous cell cancer (8, 19%). Thirty-eight patients (90%) suffered complications and there was one (2%) perioperative death. Decreasing pelvic volume was associated with deep or organ space infections (P = .01), sepsis (P = .03), and fistula (P = .05) on univariate analysis. Infections remained significant on multivariate analysis (odds ratio, 1.01; P = .02). CONCLUSIONS: Pelvic salvage surgery for recurrent malignancy is associated with a high complication rate yet low mortality. Decreasing pelvic volume is associated with increasing risk of deep or organ space infections.

Management of external ear melanoma: the same or something different?

BACKGROUND: The external ear represents a site with high ultraviolet exposure and thin skin overlying cartilage. The aim of this study was to determine if ear melanomas have different characteristics than cutaneous melanomas in other anatomic sites. METHODS: The evaluation of patients treated at a tertiary care center. RESULTS: Sixty patients were treated for ear melanoma (87% male, mean age = 56.7, mean thickness = 1.65 mm). Seven of thirty-two patients (22%) who underwent sentinel lymph node biopsy had positive nodes. Twenty (33%) patients had recurrence including 6 patients with negative sentinel lymph nodes (SLNs) and 5 patients with positive SLNs. Three of 10 patients (30%) treated with Mohs surgery had local recurrence. CONCLUSIONS: The overall local and systemic recurrences are similar to those previously reported. There is a higher recurrence rate than expected in patients with a negative SLN and a high local recurrence rate after Mohs surgery. Our data suggest that SLN evaluation may be less accurate in ear melanomas and that Mohs surgery may be associated with a relatively high local recurrence rate.

Long-term follow-up and survival of patients following a recurrence of melanoma after a negative sentinel lymph node biopsy result.

OBJECTIVE: To analyze the predictors and patterns of recurrence of melanoma in patients with a negative sentinel lymph node biopsy result. DESIGN: Retrospective chart review of a prospectively created database of patients with cutaneous melanoma. SETTING Tertiary university hospital. PATIENTS: A total of 515 patients with melanoma underwent a sentinel lymph node biopsy without evidence of metastatic disease between 1996 and 2008. MAIN OUTCOME MEASURES: Time to recurrence and overall survival. RESULTS: Of 515 patients, 83 (16%) had a recurrence of melanoma at a median of 23 months during a median follow-up of 61 months (range, 1-154 months). Of these 83 patients, 21 had melanoma that metastasized in the studied nodal basin for an in-basin false-negative rate of 4.0%. Patients with recurrence had deeper primary lesions (mean thickness, 2.7 vs 1.8 mm; P < .01) that were more likely to be ulcerated (32.5% vs 13.5%; P < .001) than those without recurrence. The primary melanoma of patients with recurrence was more likely to be located in the head and neck region compared with all other locations combined (31.8% vs 11.7%; P < .001). Median survival following a recurrence was 21 months (range, 1-106 months). Favorable characteristics associated with lower risk of recurrence included younger age at diagnosis (mean, 49 vs 57 years) and female sex (9% vs 21% for males; P < .001). CONCLUSION: Overall, recurrence of melanoma (16%) after a negative sentinel lymph node biopsy result was similar to that in previously reported studies with an in-basin false-negative rate of 4.0%. Lesions of the head and neck, the presence of ulceration, increasing Breslow thickness, older age, and male sex are associated with increased risk of recurrence, despite a negative sentinel lymph node biopsy result.

Desmoid tumors in pregnant and postpartum women.

We report here a review of the current medical literature on pregnancy associated desmoids, including 10 cases of our own. The pertinent findings are that a large percentage of desmoids in females arise in and around pregnancy. Most occur in the abdominal muscles, particularly the right rectus abdominus, perhaps related to trauma from abdominal stretching and fetal movement. While these tumors may regress spontaneously after delivery most can be surgically resected with low recurrence rates even with R1 resections and this is clearly the treatment of choice. Subsequent pregnancies do not appear to result in recurrence in either FAP or non FAP patients. It is not clear from currently available data whether pregnancy associated desmoids are molecularly distinct from other desmoids.

A neoadjuvant biochemotherapy approach to stage III melanoma: analysis of surgical outcomes.

AIMS: Completion lymph node dissection (CLND) and adjuvant therapy are recommended for node-positive melanoma patients. We sought to analyze our institution's experience with neoadjuvant biochemotherapy in stage III patients. METHODS: Clinical information was extracted from a retrospective database on stage III melanoma patients. Eligible patients received two cycles of biochemotherapy prior to their CLND. RESULTS: There were 153 patients available for analysis. The average tumor depth was 2.5 mm. More than half of all patients presented with sentinel lymph node-positive disease. Surgical complications occurred in 23% of patients. Patients who experienced an adverse event during their neoadjuvant therapy had a worse overall survival when compared with those who did not (p = 0.005). CONCLUSION: Our data suggest that aggressive neoadjuvant treatment prior to CLND does not impact surgical complications. Our surgical outcomes are similar to the current literature when adjuvant therapy is used in stage III melanoma. The inability to tolerate neoadjuvant therapy in stage III melanoma is a negative prognostic indicator.

Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition.

PURPOSE: To assess coagulation status and factor Xa inhibition in surgical intensive care unit (ICU) patients administered prophylactic unfractionated heparin for venous thromboembolism (VTE) prophylaxis. METHODS: We conducted a randomized, single-blind study at a tertiary academic medical center. Included were patients 18 years and older admitted to the surgical ICU directly after major abdominal surgery. Exclusion criteria included significant bleeding risk, preoperative anticoagulation, or history of heparin-induced thrombocytopenia. Patients were randomized to two regimens for VTE prophylaxis: standard of care unfractionated heparin, 5,000 units subcutaneously three times daily (SQH) versus unfractionated heparin via intravenous infusion, titrated to an activated partial thromboplastin time of 40-45 s (IVH). Blood samples were taken prior to surgical incision on day 0 and daily for 5 days after surgery. Samples were analyzed for factor Xa inhibition and viscoelastic whole blood clotting parameters (Sonoclot analyzer). RESULTS: A total of 50 patients were randomized to either SQH or IVH. The majority of patients had cancer. Patients in the SQH group had no detectable peak anti-factor Xa (aFXa) activity for 5 days after surgery, while patients in the IVH group had statistically elevated levels compared to the SQH group on days 3-5. SQH patients demonstrated a hypercoagulable profile on Sonoclot, while IVH patients displayed a normal profile. CONCLUSIONS: Standard of care subcutaneous dosing of unfractionated heparin for VTE prophylaxis in surgical ICU patients leads to subtherapeutic levels of factor Xa inhibition.

Preoperative capecitabine and accelerated intensity-modulated radiotherapy in locally advanced rectal cancer: a phase II trial.

OBJECTIVES: A prospective phase II trial was conducted to evaluate the feasibility, safety, and pathologic response rate of preoperative capecitabine and accelerated synchronous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with locally advanced rectal cancer. METHODS: Consenting operable patients with stage II or III adenocarcinoma of the rectum received capecitabine (825 mg/m2 PO BID, 5 days/wk x 5 weeks) and SIB-IMRT delivering 55 Gy (2.2 Gy/fraction) to the gross tumor while simultaneously delivering 45 Gy (1.8 Gy/fraction) to the regional lymph nodes and areas at risk for harboring microscopic disease. Total mesorectal excision followed 6 weeks later. A single pathologist analyzed the resected tumor's TNM stage and Mandard regression/response scores. The primary end point was pathologic complete response (pCR) rate. RESULTS: Ten subjects were enrolled, 2 of which were ineligible (1 screening failure and 1 unrelated cerebrovascular accident occurring early in treatment). The remaining 8 patients were evaluable. All 8 completed chemoradiation with strict compliance to the protocol schedule and then went on to surgical resection. At a median follow-up of 26 months (range, 15-40), all patients were alive without evidence of recurrent disease. The crude pCR rate was 38% with 50% achieving down-staging. Of 3 patients who had tumors within 5 cm of the anal verge, 2 underwent sphincter-sparing procedures. Grade 4 diarrhea occurred in 1 of 8 (13%) patients. The remaining toxicities were grade 1 or 2. CONCLUSIONS: Preoperative chemoradiation with capecitabine and SIB-IMRT is well tolerated and results in an encouraging pCR rate for patients with locally advanced rectal cancer.

Combined radiofrequency-surgical debulking of advanced abdomino-pelvic tumors.

BACKGROUND: Advanced abdomino-pelvic tumors are often unresectable using surgery alone. The current study evaluated a combination of radiofrequency (RF) ablation (RFA) and surgical debulking for such lesions. METHODS: Between July 2003 and November 2004, we treated 16 patients. Fourteen had either pelvic side wall (n = 8), sacro-iliac joint (n = 4), or vertebral (n = 2) fixation. One tumor engulfed root of mesentery, the last involved stomach-liver-vena. All patients had received prior treatment. The RF probe was placed in the center of the tumor, a 4- to 6-cm tissue core ablated, and the core curetted out or aspirated. This was repeated centrifugally out to the tumor capsule. RESULTS: Control of the target lesion for more than 6 months was achieved in 10 (62%) patients; 2 died within 3 months, and 4 had tumor progression in less than 6 months. Median survival is 18+ months. CONCLUSIONS: Combined RFA-surgical debulking was feasible and beneficial in 62%% of patients with otherwise inoperable abdomino-pelvic tumors.

Size of sentinel node metastases predicts other nodal disease and survival in malignant melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) biopsy is an indication for completion lymph node dissection (CLND) in malignant melanoma; however, most CLNDs are negative. We hypothesized SLN metastatic size of < or =2 mm would predict CLND status and prognosis. METHODS: We evaluated 80 consecutive patients undergoing CLND for positive SLNs over a 10-year period. Incidence of positive nonsentinel nodes and survival were compared for patients with SLN metastases < or =2 mm and >2 mm. RESULTS: Of 504 patients undergoing SLN biopsy, 49 patients had SLN deposits < or =2 mm and a 6% incidence of positive CLNDs. Five-year survival was 85%, essentially the same as negative SLN biopsies. In contrast, 31 had SLN metastases >2 mm, a 45% incidence of addition disease at CLND, and 5-year survival of 47% (P < .0001). CONCLUSION: An SLN metastatic cut point of 2 mm is an efficient predictor of CLND status and survival in malignant melanoma.

Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma.

PURPOSE: To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting. PATIENTS AND METHODS: Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy. The biochemotherapy regimen consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800 mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5. Growth factor support was administered with each cycle. RESULTS: Ninety-two patients were eligible for the study. At a median follow-up of 40.4 months, relapse-free survival and overall survival are 64% and 78%, respectively. There was a lower relapse rate and improved survival for patients with a positive sentinel lymph node compared with patients with clinically detected lymph nodes, although this difference did not reach statistical significance. Of the 50 patients with measurable disease, the overall response rate was 26%. Toxicity of the biochemotherapy was high but generally manageable. CONCLUSION: The current study has expanded the preliminary evidence on neoadjuvant biochemotherapy for stage III melanoma.