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Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS)., Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630., Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes., Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone., Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017., Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45)., Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies., Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery., Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases., Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022., Interventions: Nodal observation with ultrasonography rather than CLND., Main Outcomes and Measures: In-basin nodal recurrence., Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors., Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients., Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

The potentially curative treatment of sarcoma is negative margin wide resection, the clinical tumor with an en bloc margin of surrounding tissue potentially contains microscopic tumor. Planned margins should be 1 to 2 cm but can be less for oncologically equivalent barrier tissues or to preserve an adjacent critical structure. Tumor spillage should be avoided. The role of radiation and/or chemotherapy should be discussed before surgery, as there are potential benefits to preoperative administration. An isolated local recurrence is potentially curable. Amputation is rarely necessary and should only be pursued after other limb salvage treatment options have been considered., Competing Interests: Disclosure None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Heat shock proteins (hsp) are intracellular chaperones that possess extracellular immunostimulatory properties when complexed with antigens. A recombinant Hsp110-gp100 chaperone complex vaccine showed an antitumor response and prolonged survival in murine melanoma. A phase Ib dose-escalation study of a recombinant human Hsp110-gp100 vaccine in advanced-stage melanoma patients was performed to evaluate toxicity, immunostimulatory potential and clinical response. Patients with pretreated, unresectable stage IIIB/C/IV melanoma received the chaperone complex vaccine in a dose-escalation protocol; three vaccinations over a 43-day-period. Tumor response, clinical toxicity and immune response were measured. Ten patients (eight female, median age 70 years) were enrolled and two patients had grade 1 adverse events; minor skin rash, hyperhidrosis and fever (no grade 2 or higher adverse events). Median progression-free survival was longer for lower vaccine doses as compared to the maximum dose of 180 mcg (4.5 vs. 2.9 months; P = 0.018). The lowest dose patients (30 and 60 mcg) had clinical tumor responses (one partial response, one stable disease). CD8+ T cell interferon-γ responses to gp100 were greater in the clinically responding patients. A pattern of B cell responses to vaccination was not observed. Regulatory T cell populations and co-stimulatory molecules including cytotoxic T-lymphocyte-associated protein 4 and PD-1 appeared to differ in responders versus nonresponders. A fully recombinant human Hsp110-gp100 chaperone complex vaccine had minimal toxicity, measurable tumor responses at lower doses and produced peripheral CD8+ T cell activation in patients with advanced, pretreated melanoma. Combination with currently available immunotherapies may augment clinical responses., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Management of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) has historically favored liberal fluid administration owing to lengthy duration of surgery and hyperthermia. This practice has been challenged in recent years with studies demonstrating improved outcomes with restrictive fluid administration., Methods: Patients who underwent CS/HIPEC between March 2010 and September 2018 were included for analysis. Patients who received an above-median fluid rate (high-IVF) versus below-median fluid rate (low-IVF) were compared, and multivariate analyses were performed for length of stay, 90-day unplanned readmissions, and major complications., Results: The 167 patients had a mean age of 56.7 ± 11.4 years and body mass index of 29.5 ± 6.9 kg/m 2 . The median rate of total intraoperative crystalloid and colloid was 7.4 mL/kg/h. The low-IVF group had less blood loss (183 vs. 330 mL, p = 0.002), were less likely to need intraoperative vasopressor drip (2.4% vs. 11.9%, p = 0.018), and experienced fewer cardiac complications (2.4% vs. 10.7%, p = 0.031), pneumonias (0% vs. 6.0%, p = 0.024), and Clavien-Dindo grade 3-5 complications (14.5% vs. 33.3%, p = 0.004). Multivariate analyses identified bowel resection (HR 4.65, p = 0.0008) as a risk factor for 90-day unplanned readmission, while bowel resection, intraoperative fluid rate, and estimated blood loss were associated with increased length of stay., Conclusion: Higher intraoperative fluid intake was associated with multiple postoperative complications and increased length of stay, and represents a potentially avoidable risk factor for morbidity in CS/HIPEC., (© 2021. Society of Surgical Oncology.)

Introduction: Paratesticular sarcomas are defined as tumors that arise within the scrotum and include the subsites of epididymis, spermatic cord, and tunica vaginalis and represent the most common type of GU sarcoma. The mainstay of treatment is often surgical resection, combined with histology specific chemotherapy and radiotherapy. Due to the rare nature of the disease, there are limited data to guide management. We present our single-institution retrospective experience regarding the management and treatment of paratesticular sarcomas., Materials and Methods: We queried our oncology registry database for patients treated for testicular, spermatic cord, and scrotal soft tissue sarcomas between 1971 and 2017. Patients in this series had pathological confirmation of a sarcoma diagnosis by a sarcoma-specialized pathologist. Only patients with localized disease were included in this analysis with the exception of patients with a diagnosis of rhabdomyosarcoma where patients with both localized and metastatic disease were included on this study., Results: A total of 34 patients were included in this retrospective analysis. The median was 24 (range, 5-78), and the median tumor size was 6.25 cm. Twenty-six patients had localized disease (76.6%) at the time of diagnosis. A predominance of patients had tumors involving the spermatic cord (45.5%), and the most common histology was rhabdomyosarcoma (35.3%), leiomyosarcoma (26.5%), and well-differentiated liposarcoma (23.5%). The median follow-up was 71.0 months (range, 2.5-534.4 months). A total of 7 patients experienced an isolated local failure (20.6%), four patients developed distant metastatic disease (11.8%), and one patient (2.9%) with synovial sarcoma of the spermatic cord experienced a regional recurrence. The median progression-free survival (PFS) was 99.6 months, 95% CI (45.8-534.3 months), with a three-year PFS rate of 71%, 95% CI (53%-83%), and a 5-year PFS rate of 64% (range, 46%-78%). We did not find any statistically significant associations based on surgery type ( p =0.15), the use of chemotherapy, ( p =0.36), or final margin status ( p =0.21). Two patients who were treated with preoperative radiotherapy had significant wound healing complication with chronic sinus tracts, though these patients did not experience a local recurrence., Conclusions: We provide a characterization of the natural history and treatment patterns of paratesticular sarcomas. While effective at reducing a local recurrence, preoperative radiotherapy was associated with significant toxicity. As a result, we prefer the use of postoperative radiotherapy in patients as clinically indicated. We did not find any specific treatment patterns associated with an improvement in clinical outcomes., Competing Interests: The authors report no conflicts of interest with this work., (Copyright © 2021 Varun K. Chowdhry et al.)

Purpose and Methods: Completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma patients has been guideline-concordant standard of care since adoption of lymphatic mapping and SLN biopsy for the management of clinically node-negative melanoma patients more than 20 years ago. However, a trend for omission of CLND has been observed over the past decade, and we now have randomized, controlled clinical trial data to help guide treatment recommendations. Publication of these data prompted an American Society of Clinical Oncology-Society of Surgical Oncology 2018 clinical practice guideline update for these patients., Results and Conclusions: Systematic review of current evidence supports a selective, individualized approach to CLND for SLN-positive melanoma. For low-risk, low-volume micrometastatic disease, SLN biopsy may be both diagnostic and therapeutic, and close clinical follow-up with imaging or CLND are reasonable options for appropriately selected patients. For higher-risk patients, omission of CLND requires careful consideration of risks versus benefits, relevant histopathology, and individualized patient discussion. This should address patient comorbidities and life expectancy, the predicted likelihood of additional positive nodes, availability of imaging surveillance, likelihood of adherence to imaging and clinical follow-up, consequences of regional recurrence, and the prognostic value of complete nodal staging and its impact on adjuvant therapy recommendations or clinical trial participation. Data on long-term outcomes, cost, and patient-reported quality of life measures are not yet available.

Background: Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection., Methods: Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)., Results: Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p =0.017; HR 4.16, p =0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS., Conclusions: PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1 α signaling, and a p53 nuclear accumulation DNA damage response., Clinical Trial Registration: NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is NCT00002791.

A negative sentinel lymph node biopsy (SLNB) for stage IB (T1b/T2a N0) melanoma would predict an excellent long-term prognosis. Combined with the concept of conditional survival, an "abbreviated" cancer surveillance strategy was implemented to reduce the number of visits and total length of follow-up. Retrospective review of all pathologic stage IB melanoma patients (negative SLNB) at a single institution between 2006 and 2008 after implementation of an "abbreviated" cancer surveillance; clinic visits every six months for five years followed by one annual visit (total follow-up six years). Patient demographics, tumor characteristics, and information regarding recurrences were obtained. Recurrence-free, disease-specific, and overall survival were calculated. Eighty-seven patients underwent the "abbreviated" cancer surveillance. Median age was 55.4 years and 50.6 per cent were male. Median Breslow thickness was 1.1 mm (range 0.5-2.0 mm) and 1.1 per cent were ulcerated. Primary tumor site was 49 per cent extremities, 39 per cent trunk, and 12 per cent head/neck. Median follow-up was 68.6 months. Five-year recurrence-free, disease-specific, and overall survivals were 89, 95, and 88 per cent, respectively. During surveillance, 10 patients had concerning symptoms or physical findings prompting subsequent workup, all of which were negative for recurrence/metastases. There were only three true melanoma recurrences; all were distant metastases and presented symptomatically between scheduled follow-up visits. In light of the excellent prognosis for pathologic (SLNB negative) stage IB melanoma, an "abbreviated" cancer surveillance schedule based on conditional survival would reduce both direct and indirect costs in this cohort. The few recurrences were symptomatic and unlikely to have changed with more intensive surveillance.

Background: Cytoreductive surgery and heated intraperitoneal chemotherapy (CS/HIPEC) is performed for selected indications at a limited number of specialized centers worldwide. Currently there is no standardized approach to the perioperative care process. We sought to capture current practices in the perioperative management of patients who undergo CS/HIPEC at high-volume centers., Methods: Surgeon members of the American Society of Peritoneal Surface Malignancies working at high-volume CS/HIPEC centers (>10 cases/year) were invited to complete an online survey. The survey included questions relating to preoperative preparation of patients, intraoperative practices, and postoperative care., Results: Ninety-seven surgeons from five continents completed the survey (response rate 55%). The majority (80%) practiced in academic environments. Most respondents (68%) indicated that a formal preoperative preparatory pathway for CS/HIPEC surgery existed at their centers, but few (26%) had used enhanced recovery protocols in this group of patients. Whereas the intraoperative technical practices of the CS/HIPEC procedure were relatively consistent across respondents, there was little agreement on pre- and postoperative care practices, including use of mechanical bowel preparation, nutritional supplementation, methods of perioperative analgesia, timing of physical therapy and ambulation, nasogastric tube and Foley removal, intravenous fluids, blood transfusion parameters, and postoperative use of deep-vein thrombosis prophylaxis and antibiotics., Conclusions: Perioperative care practices for CS/HIPEC are widely variable nationally and internationally. Standardization of such practices offers an opportunity to incorporate evidence-based interventions and may enhance patient outcomes and improve care standards across all centers that offer this procedure.

Objectives: Treatment of locally advanced unresectable or metastatic cutaneous squamous cell carcinoma (mCSCC) is suboptimal with a paucity of robust data on systemic therapy. This retrospective study aimed to evaluate the efficacy and outcomes of patients with locally advanced unresectable or mCSCC treated with systemic therapy., Methods: Records of patients with CSCC treated with systemic therapy from January 2001 to January 2011 were reviewed. Response was assessed using WHO criteria. Descriptive results were assessed using Wilcoxon rank-sum test for ordinal responses and Pearson χ test for categorical responses. Survival was calculated by the Kaplan-Meier method., Results: Of 28 patients identified, 25 patients (M:F=18:7), median age 66 years (range, 39 to 85 y), had the required data for final analysis. Partial response was 44% and stable disease (SD) was 24%. The median progression-free survival (PFS) and overall survival (OS) were 5.5 months (2.3, 13.2) and 10.9 months (5.3, 21.3) respectively; 3-year OS was 22%. Patients with WHO response had improved PFS (20.8 mo; 4.4, NR) and OS (37.5 mo; 10.3, NR) compared with patients with SD/PD (PFS 2.7 mo; OS 5.9 mo). Use of platinum-based therapy significantly improved PFS and OS, whereas taxanes and cetuximab had no impact in this small cohort. There was no difference in PFS or OS with multiagent versus single-agent therapy., Conclusions: Platinum-based therapy remains as one of the standard options in advanced CSCC management. Agents to improve response rates are needed and future trials should address the use of novel targeted and new chemotherapy combinations in CSCC.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy., (Copyright © 2016 by the National Comprehensive Cancer Network.)

Purpose: Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams., Methods: Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics., Results: HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection., Conclusions: Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.

Background: Given the propensity for hematogenous metastases, neoadjuvant chemotherapy (NAC) could treat occult metastatic disease early, potentially improving survival and better defining which primary angiosarcomas (AS) benefit from surgical resection., Methods: A retrospective comparison was performed of 23 patients with resectable, localized cutaneous/soft tissue primary AS treated with surgery alone (S, n = 13) or NAC followed by surgery (NAC-S, n = 12)., Results: Primary sites included breast/chest (n = 9), head/neck (n = 9), extremity (n = 3), and other (n = 2). 23% S versus 40% NAC-S had prior radiation (RT). NAC regimens were paclitaxel (n = 6) or gemcitabine/docetaxel (n = 4). Seventy percent were high grade. Distant metastases were found in 17% after NAC. Non-primary wound closure was required in 54 %S versus 30%NAC-S (P = 0.4). R0 resections were achieved in 85% S versus 80% NAC-S (30% had a complete pathologic response). Two-year local recurrence (LR)-free, disease-free, and overall survivals were 67.1, 38.5, and 61.5% for S versus 68.6, 54.9, and 68.6% for NAC-S (P = 0.52, 0.67, and 0.58). The mean number of surgical resections/patient to maintain local control was 1.8 S versus 1.3 NAC-S (P = 0.06)., Conclusions: NAC for primary AS was well tolerated. Although there was no statistically significant survival benefit, NAC helped define who would benefit from surgical resection., (© 2015 Wiley Periodicals, Inc.)

There is overlap in the clinical presentation of benign soft tissue tumors and soft tissue sarcomas. A preoperative sarcoma diagnosis would allow for consideration for neoadjuvant therapy, including preoperative radiation, as well as optimal surgical treatment planning, and patient counseling. Image guided core needle biopsy is a low morbidity, cost-effective, highly accurate approach for obtaining a definitive pathologic diagnosis. Any biopsy approach should minimize the potential for tumor seeding of otherwise uninvolved anatomic structures., (© 2015 Wiley Periodicals, Inc.)

Introduction. Superficial soft tissue sarcomas (S-STS) are generally amenable to wide excision. We hypothesized that local recurrence (LR) should be low, even without radiation therapy (RT), and sought to examine the contribution of depth to LR and OS. Methods. Patients with S-STS were retrospectively reviewed. Demographics, tumor features, treatment received, and outcomes were analyzed. Results. 103 patients were identified. Median age was 55 years; 53% of patients were female. Tumor site was 39% in trunk, 38% in the lower extremity, 14% in the upper extremity, and 9% in other locations. The most common histology was 36% leiomyosarcoma. Median tumor size was 2.8 cm (range 0.2-14 cm). Sixty-six percent of tumors were of intermediate/high grade. RT was administered preoperatively in 6% of patients and postoperatively in 15% of patients. An R0 resection was accomplished in 92%. At a median follow-up of 34.2 months (range 2.3-176), 9 patients had a LR (8.7%). Tumor size and grade were not associated with LR. OS was not associated with any tumor or patient variables on univariate analysis. Conclusions. LR was low for S-STS, even with large or high grade tumors and selective use of RT. Surgical resection alone may be adequate therapy for most patients. Superficial location seems to supersede other factors imparting a good prognosis for this group of tumors.

Although melanoma was historically thought to be radiation resistant, there are limited data to support the use of adjuvant radiation therapy for certain situations at increased risk for locoregional recurrence. High-risk primary tumor features include thickness, ulceration, certain anatomic locations, satellitosis, desmoplastic/neurotropic features, and head and neck mucosal and anorectal melanoma. Lentigo maligna can be effectively treated with either adjuvant or definitive radiation therapy. Some retrospective and prospective randomized studies support the use of adjuvant radiation to improve regional control after lymph node dissection for high-risk nodal metastatic disease. Consensus on the optimal radiation doses and fractionation is lacking., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib., (Copyright © 2014 by the National Comprehensive Cancer Network.)

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

The clinical practice of hyperthermic intraperitoneal chemoperfusion (HIPEC) for carcinomatosis has lacked preclinical justification. A standardized mouse model was created to evaluate the independent effects of intraperitoneal chemotherapy. Diffuse colorectal carcinomatosis was generated in mice prior to intraperitoneal lavage with mitomycin C (MMC) at clinically comparable dosing for variable lengths of time. Tumor volumes, MMC tissue concentrations and survival were measured in comparison to saline lavage and intravenous MMC. Magnetic resonance imaging revealed a direct correlation between tumor volume, MMC dose and exposure time and survival. Intravenous MMC demonstrated a rapid clearance from the blood, lower peritoneal tissue concentrations, less tumor growth inhibition and decreased survival compared to intraperitoneal administration. Intraperitoneal chemotherapy inhibited tumor growth independent of cytoreduction or hyperthermia, demonstrated improved peritoneal tissue concentration and was associated with increased survival. These data support the clinical utility of the intraperitoneal chemotherapy component of HIPEC.

The risks and benefits of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CS/HIPEC) continue to be debated by the oncology community. A retrospective analysis of contemporary data (2003-2011) was performed to provide objective information regarding surgical morbidity, mortality, and survival for patients undergoing CS/HIPEC at a comprehensive cancer center. While procedure-associated morbidity was comparable to other major surgical oncology procedures, there was no operative or 30-day mortality and 60-day mortality was 2.7%. Increasing numbers of bowel resections were found to correlate to an increased incidence of deep surgical site infections (including abscess and enterocutaneous fistula) and need for reoperation which was in turn associated with a decreased overall survival (OS) and progression-free survival (PFS). Five-year OS rates varied by site of tumor origin and histology (disseminated peritoneal adenomucinosis [91.3%], Mesothelioma [80.8%], Appendiceal Adenocarcinoma [38.7%], and Colorectal Adenocarcinoma [38.2%]). With an acceptable morbidity and mortality rate, CS/HIPEC should be included as an effective treatment modality in the multidisciplinary care of select patients with peritoneal metastases.

Background: Isolated limb perfusion (ILP) for extremity melanoma has been used clinically for over half a century. Mouse modeling of ILP may offer significant experimental advantages compared with existing models. We propose a novel mouse model and report our initial experience., Methods: We injected female C57BL/6 mice (22-25 g) with 1 × 10(6) B16 melanoma cells subcutaneously in the distal right thigh. After 7 d of tumor establishment, we cannulated the superficial femoral artery (inflow) and vein (outflow) of anesthetized mice and placed a proximal tourniquet. Non-oxygenated perfusate included low-dose or high-dose melphalan and saline (control). We analyzed endpoints of cannulation time, procedural complications, morbidity, toxicity, and tumor response., Results: We performed 11 superficial femoral vessel cannulations. Median cannulation time was 19 min (range, 15-32 min). Intact perfusion models were obtained in 10 of 11 cases (91%); one case failed owing to superficial femoral vein dissection. Morbidity rate was 20% (one wound dehiscence and one hematoma). Both high- and low-dose melphalan perfusion groups (4 mice/group) trended to growth delay and regression compared with saline-perfused groups. Toxicity was greater in the high-dose melphalan-treated mice., Conclusions: We have established the first reproducible mouse model of ILP for melanoma. Future experiments will take advantage of the large number of established mouse knockout models and reagents to dissect the precise mechanisms of tumor control after ILP, and examine to novel agents., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

The relationship between surgical margin status and outcomes in sarcoma has been an area of controversy for years. Some question whether a positive margin represents inadequate surgery or perhaps is a marker of aggressive cancer biology. This article reviews the literature regarding the natural history of positive margins and its possible influence on sarcoma recurrence and survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8 cm, intermediate/high grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of 49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B. Grade 3/4 venous thromboembolic (VTE) events: 40% cohort A (1 catheter thrombus and 5 DVT or PE) versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.

We previously reported that scavenger receptor A (SRA/CD204), a binding structure on dendritic cells (DCs) for large stress/heat shock proteins (HSPs; e.g., hsp110 and grp170), attenuated an antitumor response elicited by large HSP-based vaccines. In this study, we show that SRA/CD204 interacts directly with exogenous hsp110, and lack of SRA/CD204 results in a reduction in the hsp110 binding and internalization by DCs. However, SRA(-/-) DCs pulsed with hsp110 or grp170-reconstituted gp100 chaperone complexes exhibit a profoundly increased capability of stimulating melanoma Ag gp100-specific naive T cells compared with wild-type (WT) DCs. Similar results were obtained when SRA/CD204 was silenced in DCs using short hairpin RNA-encoding lentiviruses. In addition, hsp110-stimulated SRA(-/-) DCs produced more inflammatory cytokines associated with increased NF-κB activation, implicating an immunosuppressive role for SRA/CD204. Immunization with the hsp110-gp100 vaccine resulted in a more robust gp100-specific CD8(+) T cell response in SRA(-/-) mice than in WT mice. Lastly, SRA/CD204 absence markedly improved the therapeutic efficacy of the hsp110-gp100 vaccine in mice established with B16 melanoma, which was accompanied by enhanced activation and tumor infiltration of CD8(+) T cells. Given the presence of multiple HSP-binding scavenger receptors on APCs, we propose that selective scavenger receptor interactions with HSPs may lead to highly distinct immunological consequences. Our findings provide new insights into the immune regulatory functions of SRA/CD204 and have important implications in the rational design of protein Ag-targeted recombinant chaperone vaccines for the treatment of cancer.

Background: Although often proposed as a means to reduce the harmful consequences of tumor spill, water lavage has yet to be systematically evaluated in relevant in vitro and in vivo models. This study evaluates the mechanisms and utility of a single water lavage to improve the sequelae of tumor spill during laparotomy., Methods: Murine colorectal tumor cell susceptibility to water-induced osmotic lysis was characterized in vitro. A reproducible model of tumor spill was established to recapitulate water or saline lavage during laparotomy. Analyses of tumor volumes calculated from noninvasive imaging were performed. The tumor volumes and survival of mice treated with water, normal saline, or sham laparotomy were assessed., Results: Significant osmotic lysis of cultured murine colorectal cancer cells was observed after a brief exposure to water. Compared to saline or sham laparotomy, water lavage demonstrated superior clinical outcomes with a decrease in tumor burden and concomitant improvement in survival., Conclusions: The use of water lavage during oncologic surgeries to reduce the sequelae of tumor spill is justified and strongly supported by our study. Data from our study raise several concerns regarding the mechanisms and efficacy of saline lavage. Clinically, the use of water lavage during laparotomy would be anticipated to reduce peritoneal disease burden with minimal toxicity or cost.

Objective: To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms., Background: Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms., Methods: We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and dactinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Regional toxic effects were measured using the Wieberdink scale and serum creatinine phosphokinase levels., Results: The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months., Conclusions: Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet durability of response is unknown.

Background: Thick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up., Methods: 155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS)., Results: Median patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients--15.4%), elective lymph node dissection (ELND) (24 patients--17.6%) or SLNB (91 patients--67%). 75% of ELND's and 53% of SLNB's were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively)., Conclusion: Within the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).

Background: In-transit metastases of Merkel cell carcinoma (MCC) are an unusual and therapeutically challenging manifestation of the disease. Given the similarity to melanoma, in-transit MCC may be amenable to isolated regional therapy., Objective: To present a case series of 12 patients who underwent isolated limb perfusion (ILP) or isolated limb infusion (ILI) for in-transit MCC., Methods: A literature search was conducted using Medline and Pubmed databases for MCC, ILP, and ILI as key words. Ten cases were identified and reviewed; two cases from our hospital were also included in the series., Results: Nine patients underwent ILP, and three were treated with ILI. Eleven patients had a complete clinical response, and one had a partial response. All patients avoided limb amputation. Mean follow-up was 25.3 months. Mean duration of response was 21.8 months. Four patients relapsed regionally. Two patients developed distant metastases and died of their disease., Conclusion: This is the largest case series of in-transit MCC treated with ILP or ILI. Both techniques appear to be a low-morbidity alternative to amputation for the treatment of isolated extremity in-transit MCC. ILI is less invasive than ILP and may be a more practical first-line treatment option. The authors have indicated no significant interest with commercial supporters., (© 2011 by the American Society for Dermatologic Surgery, Inc.)

Objectives: Dermatofibrosarcoma protuberans (DFSP) is a spindle cell tumor with a high local recurrence rate. Wide excision (WE) has been the standard treatment, but ideal margin width is poorly defined and Mohs micrographic surgery (MMS) has emerged as an alternative procedure. This study examines the use of WE versus MMS for the treatment of primary DFSP at a single institution., Methods: Retrospective review of 48 primary DFSP cases treated from 1971 to 2006. Patient demographics, tumor features, surgical modality (WE vs. MMS), final pathology, and clinical outcome were evaluated., Results: Twenty-eight patients underwent WE versus 20 patients for MMS. Median age was 40 years. Median WE margin width was 2 cm. For MMS, the median number of layers required to clear the tumor was 2. Median maximal defect size was 10 cm for WE versus 9.4 cm for MMS. Advanced closure techniques were required for 18% WE versus 65% MMS (P = 0.001). Median operative time was significantly lower for WE at 77 minutes versus 257 minutes for MMS (P < 0.001). Positive margins were present in 21.4% (6/28) WE versus 0% MMS (P = 0.01). At a median follow-up of 49.9 months for WE and 40.4 months for MMS, local recurrence rates were 3.6% (1/28) and 0%, respectively (P = 1.0)., Conclusions: From a surgical standpoint, WE was faster than MMS and resulted in a less complex defect/closure. Although positive margin resection was more common with WE, local control was ultimately similar for the 2 surgical modalities. The choice of WE versus MMS should be based on individualized patients/tumor characteristics and institutional expertise in these modalities.

Background: The objective of this study was to evaluate the impact of adjuvant radiation therapy (RT) on regional recurrence and survival after therapeutic lymphadenectomy (TL) for clinically advanced, lymph node-metastatic melanoma., Methods: Six hundred fifteen patients who had clinically advanced, regional lymph node-metastatic disease underwent TL. All patients were appropriate potential candidates for adjuvant RT (enlarged or multiple positive lymph nodes, extracapsular extension) because of a high risk for regional recurrence regardless of whether or not they received RT. Patient-related, tumor-related, and treatment-related variables that were associated with recurrence, survival, and treatment-related morbidity with and without RT were analyzed., Results: The median follow-up was 5 years. The actuarial 5-year regional lymph node basin control rate was 81%. On multivariate analysis, the number of positive lymph nodes, the number of lymph nodes removed, and the use of adjuvant RT were associated with improved regional control. Treatment-related morbidity, particularly lymphedema, was increased with the use of adjuvant RT and an inguinal site of lymph node metastases. At last follow-up, 268 patients were alive with actuarial 5-year distant metastasis-free survival (DMFS) and disease-specific survival (DSS) rates of 40% and 48%, respectively. On multivariate analysis, DMFS and DSS both were influenced by the number of positive lymph nodes and the number of lymph nodes removed. In addition, DSS was influenced by primary tumor thickness and the receipt of adjuvant RT., Conclusions: Adjuvant RT was associated with improved regional lymph node basin control compared with TL alone in patients with high-risk, clinically advanced, lymph node-metastatic melanoma. Although it is a regional therapy, adjuvant RT also may have an impact on DSS., (Copyright (c) 2009 American Cancer Society.)

Aims: To identify clinicopathologic and treatment variables associated with long-term overall survival (OS) in soft tissue sarcoma (STS) patients with lung metastases undergoing pulmonary metastasectomy (PM)., Methods: Retrospective review of 94 STS PM patients with an actual follow-up > or = 5 years. Data were collected on demographics, tumor features, treatment, and outcome., Results: Most primary tumors were intermediate/high grade and the common histopathologies were evenly distributed. Half of the primary tumors were located on the extremities. The mean disease-free interval (DFI) from time of original diagnosis until metastases was 25 months (median 15 months). Eighteen patients had synchronous metastatic disease. Bilateral pulmonary metastases and >1 metastasis were common. The median number of metastases resected was 2.5. Thirty-four patients had extrapulmonary tumor at the time of PM; all extrapulmonary disease was resected. Negative margin resection (R0) PM was performed in 74 patients. Actual 5-year disease-free survival (DFS) and OS for all patients were 5% and 15%, respectively. For the R0 group, actual 5-year DFS and OS were 7% and 18%, respectively. R0 resection and a prolonged DFI were associated with improved OS. Patient characteristics, tumor features, local recurrence, and adjuvant therapy did not affect OS., Conclusions: Less than 20% of STS PM patients will survive 5 years. Complete resection and DFI are the most predictive factors for prolonged survival.

Background: Nevus spilus is a rare, acquired, and often large cutaneous lesion consisting of a light brown background macule containing varying numbers of small darker macular or papular areas., Objective: Nevus spilus may contain dysplastic melanocytic elements, and there are also reports of melanoma arising from nevus spilus. However, the absolute risk for malignant transformation is not well defined., Conclusion: We discuss a case of synchronous melanomas arising from a nevus spilus and potential management recommendations based on a review of the pertinent literature.

The surgeon's role in the treatment of malignant peritoneal disease has expanded over time, stemming from a better understanding of tumor biology. For the majority of patients, carcinomatosis is a terminal process with surgical intervention being reserved for palliation of bowel obstruction or symptomatic ascites. However, for select patients with favorable tumor biologies, aggressive surgical approaches may result in long-term survival. This review describes the patterns of peritoneal tumor dissemination, surgical palliation of malignant bowel obstruction or ascites, and the principles, indications, toxicities, and overall results of cytoreductive surgery with intraperitoneal hyperthermic chemotherapy. On the other hand, long-term survival is rarely expected for malignant pleural disease unless the causal tumor is highly responsive to systemic chemotherapy. There are controversies and considerable geographic variations in the management of malignant pleural effusions. However, less invasive ambulatory palliative treatments for patients so afflicted are gaining popularity.

Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma., Patients and Methods: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status., Results: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively)., Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

The inflammatory phenotype of genetically modified mice is complex, and the role of Gram-negative lipopolysaccharide (LPS) in acute inflammation induced by surgical cannulation trauma, alone or in combination with hemorrhage and resuscitation ("hemorrhagic shock"), is both complex and controversial. We sought to determine if a mathematical model of acute inflammation could elucidate both the phenotype of CD14-deficient (CD14(-/-)) mice--following LPS, cannulation, or hemorrhagic shock--and the role of LPS in trauma/hemorrhage-induced inflammation. A mathematical model of inflammation initially calibrated in wild-type (C57Bl/6) mice subjected to LPS, cannulation, and hemorrhagic shock was recalibrated in CD14(-/-) mice subjected to the same insults, yielding an ensemble of models that suggested specific differences at the cellular and molecular levels (for example, 43-fold lower activation of leukocytes by LPS). The CD14(-/-)-specific model ensemble could account for complex changes in inflammatory analytes in these mice following LPS treatment. Model prediction of similar organ damage in CD14(-/-) and wild-type mice subjected to cannulation alone or with hemorrhagic shock was verified in vivo (similar ALT levels). These studies suggest that LPS-CD14 responses do not cause inflammation in surgical trauma/hemorrhagic shock and demonstrate a novel use of combined in silico and in vivo methods to elucidate the complex inflammatory phenotype of genetically modified animals.

Background: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial. Incorporating other prognostic factors (Clark level and ulceration), we evaluated the 6th edition American Joint Committee on Cancer (AJCC) clinical stage as a simple and widely applicable guideline for offering SLN biopsy for thin melanoma., Methods: This study was a review of a prospective melanoma SLN database from 1993 to 2003 with emphasis on SLN positivity rates based on the 6th edition AJCC primary tumor thickness intervals and clinical stage., Results: Three hundred five patients underwent SLN biopsy, with an overall positivity rate of 17.7%. By the 6th edition AJCC, lesions < or = 1.00 mm had an SLN positivity rate of 6.6%. By 6th edition clinical stage, SLN positivity rates were 4.9% for stage IA and 10.4% for stage IB. By using stage IA as the criterion for not offering SLN biopsy, this procedure would have been avoided in 46% (39 of 85) of < or = 1.00-mm melanoma patients with a negative SLN., Conclusions: Sixth edition AJCC clinical stage IB as a selection criterion for performing SLN biopsy in thin melanoma identifies most patients with a positive SLN while also avoiding a negative SLN biopsy in many patients. Until additional widely accepted and validated selection criteria are available, SLN biopsy for clinical stage IB, but not stage IA, thin melanomas is a reasonable approach.

Purpose of Review: To examine the factors predictive of recurrence for soft tissue sarcomas, the role of salvage therapy, and the data in support of current surveillance strategies., Recent Findings: There are multiple primary tumor characteristics and other factors that can stratify patients into low- or high-risk groups for developing recurrent disease. The available data also support a limited role for salvage therapy in the setting of isolated local recurrence or distant metastases. The use of routine chest computed tomography as opposed to conventional chest x-ray for pulmonary surveillance is costly and provides little additional benefit if the risk for lung metastases is low. When examined scientifically, standard laboratory studies and surveillance imaging of the primary tumor site for extremity soft tissue sarcomas add little to the detection of recurrent disease. In addition to predictive variables, physician experience and opinion influence surveillance strategies., Summary: For soft tissue sarcomas, patient education and office visits with thorough history and physical examination will detect the vast majority of recurrent disease. Routine surveillance imaging is only of significant benefit if the risk for asymptomatic recurrence is high or if other factors make clinical assessment difficult. There is no benefit to basic laboratory studies in standard follow-up regimens.

At the present time, standard therapy for potentially curable rectal cancer consists of transabdominal surgical resection and adjuvant chemoradiation for American Joint Committee on Cancer stage II/III disease. Controversial issues include the use of local excision as opposed to formal resection and total mesorectal excision (TME) alone without adjuvant therapy. Although early stage tumors are the ideal potential candidates for local excision, clinical staging with endoscopic ultrasound is extremely variable in accurately predicting T and N stage. In addition, even low-grade or T1 tumors are associated with a 7% to 14% chance of nodal metastatic disease. Overall, the risk for local recurrence is higher after local excision but may be reduced by adjuvant therapy. Salvage rates for recurrent disease range from 21% to 91%. In regard to TME, local recurrence rates are an impressive 0% to 12% without adjuvant radiation. However, the addition of radiation therapy may further reduce these already low rates, especially in higher-risk groups. The results of 2 large European studies show acceptable complication rates and the applicability of this technique to a diverse patient population.

Nitric oxide (NO) can modulate numerous genes directly; however, some genes may be modulated only in the presence of the inflammatory stimuli that increase the expression of the inducible nitric oxide synthase (iNOS). One method by which to examine changes in NO-mediated gene expression is to carry out a gene array analysis on NO-nai;ve cells. Herein, we report a gene array analysis on mRNA from iNOS-null (iNOS(-/-)) mouse hepatocytes harvested from mice exposed to NO by infection with an adenovirus expressing human iNOS (Ad-iNOS). Of the 6500 genes on this array, only approximately 200 were modulated either up or down by the increased iNOS activity according to our criteria for significance. Several clearly defined families of genes were modulated, including genes coding for proinflammatory transcription factors, cytokines, cytokine receptors, proteins associated with cell proliferation and cellular energetics, as well as proteins involved in apoptosis. Our results suggest that iNOS has a generally anti-inflammatory and anti-apoptotic role in hepatocytes but also acts to suppress proliferation and protein synthesis. The expression of iNOS results in increased expression of stress-related proteins, including heme oxygenase-1 (HO-1). We used HO-1 to confirm that a significant change identified by an analysis could be demonstrated as significant in cells and tissues. The elevation of HO-1 was confirmed at the protein level in hepatocytes in vitro. Furthermore, iNOS(-/-) mice experienced greatly increased liver injury subsequent to intestinal ischemia/reperfusion injury, associated with an inability to upregulate HO-1. This is the first study to address the global gene changes induced by iNOS in any cell type, and the findings presented herein may have clinical relevance for conditions such as septic or hemorrhagic shock in which hepatocytes, NO, and HO-1 play a crucial role.

The survival of patients undergoing liver resection for colorectal metastases is poor in the presence of extrahepatic disease. Therefore identification of periportal and celiac lymph node metastases is central to proper patient selection. In this study we examined the technique of intraoperative hepatic lymphatic mapping with isosulfan blue dye in humans. Intrahepatic dye injection was performed in patients undergoing surgical exploration for colorectal liver metastases. The location of all blue-stained lymphatics and lymph nodes was recorded. All stained and unstained lymph nodes were biopsied for pathologic examination. Thirteen intraoperative lymphatic mapping procedures were performed in 11 patients. A blue-stained lymphatic was visualized in 11 of 13 injections (85%). A blue lymph node was visualized in seven of 13 injections (54%). Three of the seven blue nodes (43%) were not detected by the surgeon before the mapping procedure. There were no complications associated with the intrahepatic dye injections. All biopsied lymph nodes were negative for metastatic tumor. We conclude that intraoperative hepatic lymphatic mapping with isosulfan blue dye is a simple, rapid, and safe technique in humans. It may serve as an adjunct to random lymph node biopsy for the identification of periportal and celiac nodal metastases before liver resection in patients with metastatic colorectal carcinoma.