Surgical Management of Retroperitoneal Sarcoma.

Surgery is the cornerstone of treatment for retroperitoneal sarcoma (RPS). Surgery should be performed by a surgical oncologist with sub-specialization in this disease and in the context of a multidisciplinary team of sarcoma specialists. For primary RPS, the goal of surgery is to achieve the complete en bloc resection of the tumor along with involved organs and structures to maximize the clearance of the disease. The extent of resection also needs to consider the risk of complications. Unfortunately, the overarching challenge in primary RPS treatment is that even with optimal surgery, tumor recurrence occurs frequently. The pattern of recurrence after surgery (e.g., local versus distant) is strongly associated with the specific histologic type of RPS. Radiation and systemic therapy may improve outcomes in RPS and there is emerging data studying the benefit of non-surgical treatments in primary disease. Topics in need of further investigation include criteria for unresectability and management of locally recurrent disease. Moving forward, global collaboration among RPS specialists will be key for continuing to advance our understanding of this disease and find more effective treatments.

Pyramidal Decision Support Framework Leverages Subspecialty Expertise across Enterprise to Achieve Superior Cancer Outcomes and Personalized, Precision Care Plans.

The complexity of cancer care requires integrated and continuous support to deliver appropriate care. An expert network with complementary expertise and the capability of multidisciplinary care is an integral part of contemporary oncology care. Appropriate infrastructure is necessary to empower this network to deliver personalized precision care to their patients. Providing decision support as cancer care becomes exponentially more complex with new diagnostic and therapeutic choices remains challenging. City of Hope has developed a Pyramidal Decision Support Framework to address these challenges, which were exacerbated by the COVID pandemic, health plan restrictions, and growing geographic site diversity. Optimizing efficient and targeted decision support backed by multidisciplinary cancer expertise can improve individual patient treatment plans to achieve improved care and survival wherever patients are treated.

Emotional Distress and Financial Toxicity in Younger Adult Patients Undergoing Oncologic Surgery.

BACKGROUND: There has been an alarming increase in the number of young adults (YA) diagnosed with cancer. The emotional, psychosocial, and financial distress experienced by newly diagnosed YA undergoing cancer surgery remains largely unknown. METHODS: A validated biopsychosocial distress screening tool (SupportScreen) was administered to patients diagnosed with cancer before surgery between 2009 and 2017 in a National Cancer Institute Comprehensive Cancer Center. Patients were stratified into YA less than or equal to 45 years and older adults (OA) above 45 years. Descriptive statistics and logistic regression were used to analyze distress outcomes. RESULTS: In total, 4297 patients were identified, with YA comprising 13.3% (n=573) of the cohort. YA reported higher emotional distress, including increased anxiety (33.8% vs 27.4%, P =0.002), greater fear of procedures (26.7% vs 22%, P =0.018), and difficulty managing emotions (26% vs 20.7%, P =0.006). YA struggled more frequently to manage work/school (29.5% vs 19.3%, P <0.001), finding resources (17.8% vs 11.8%, P <0.001), changes in physical appearance (22.2% vs 13.4%, P <0.001), fatigue (36% vs 27.3%, P <0.001), and ability to have children (18.4% vs 3%, P <0.001). Financial toxicity was significantly higher in the YA group (40.5% vs 28%, P <0.001). While income level was strongly protective against emotional distress and financial toxicity in OAs, it was less protective against the risk of financial toxicity in YA. Younger age was an independent predictor of financial toxicity in a model adjusted to income (odds ratio=1.52, P =0.020). CONCLUSIONS: YA in the prime of their personal and professional years of productivity require special attention when undergoing surgical evaluation for cancer. Resource allocation and counseling interventions should be integrated as part of their routine care to expedite their return to optimal physical and holistic health and mitigate psychosocial distress and financial toxicity.

National postoperative and oncologic outcomes after pelvic exenteration for T4b rectal cancer.

BACKGROUND AND OBJECTIVES: Studies reporting outcomes after pelvic exenteration for rectal cancer are limited. The objective of this study was to evaluate early postoperative and oncologic outcomes in a national multi-institutional cohort. METHODS: Using the National Cancer Database (NCDB), which collects data from over 1500 commission on cancer (CoC)-accredited hospitals, we analyzed patients undergoing pelvic exenteration for T4b rectal adenocarcinoma. RESULTS: There were 1367 pelvic exenterations performed in 552 hospitals. Median age was 60 years, the majority of patients (n = 831; 60.8%) were female. Neoadjuvant radiation was used only in 57%; 24.3% of resections had positive margins. Following exenteration, 30-day mortality rate, 90-day mortality rate, and readmission rates were: 1.8%, 4.4%, and 7.4%. Age ≥ 60 years and higher Charlson-Deyo comorbidity index were independently associated with increased 90-day mortality (P < .001). Overall survival (OS) was 50 months. After adjustment of significant covariates, negative margin status (adjusted HR, 0.6, 95% CI, 0.5-0.8; P < .001) and receipt of perioperative radiation or chemoradiation (adjusted HR, 0.5; 95% CI, 0.4-0.6; P < .001) were significantly associated with decreased risk of death. Only 71% of the patients received perioperative radiation. CONCLUSIONS: Pelvic exenterations are being performed safely in Coc-accredited hospitals. However, up to one fourth of patients undergo resections with positive margins or are subject to underutilization of perioperative radiation therapy. Increased use of radiation may increase negative margin resections and improve patient outcomes.

Enhanced Recovery after Surgery for Gastric Cancer Patients Improves Clinical Outcomes at a US Cancer Center.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols for gastric cancer patients have shown improved outcomes in Asia. However, data on gastric cancer ERAS (GC-ERAS) programs in the United States are sparse. The purpose of this study was to compare perioperative outcomes before and after implementation of an GC-ERAS protocol at a National Comprehensive Cancer Center in the United States. MATERIALS AND METHODS: We reviewed medical records of patients surgically treated for gastric cancer with curative intent from January 2012 to October 2016 and compared the GC-ERAS group (November 1, 2015-October 1, 2016) with the historical control (HC) group (January 1, 2012-October 31, 2015). Propensity score matching was used to adjust for age, sex, number of comorbidities, body mass index, stage of disease, and distal versus total gastrectomy. RESULTS: Of a total of 95 identified patients, matching analysis resulted in 20 and 40 patients in the GC-ERAS and HC groups, respectively. Lower rates of nasogastric tube (35% vs. 100%, P<0.001) and intraabdominal drain placement (25% vs. 85%, P<0.001), faster advancement of diet (P<0.001), and shorter length of hospital stay (5.5 vs. 7.8 days, P=0.01) were observed in the GC-ERAS group than in the HC group. The GC-ERAS group showed a trend toward increased use of minimally invasive surgery (P=0.06). There were similar complication and 30-day readmission rates between the two groups (P=0.57 and P=0.66, respectively). CONCLUSIONS: The implementation of a GC-ERAS protocol significantly improved perioperative outcomes in a western cancer center. This finding warrants further prospective investigation.

NCCN Guidelines Insights: Melanoma, Version 3.2016.

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

Underreporting of Gastrointestinal Stromal Tumors: Is the True Incidence Being Captured?

BACKGROUND: Hospital cancer registries are only required to report gastrointestinal stromal tumors (GISTs) if labeled malignant or metastatic, leading to potential loss of cases in national cancer registries. Our objective was to determine whether GISTs are underreported in the US. METHODS: Retrospective review of pathology reports between 2010 and 2013 with diagnosis of GIST was performed at two academic medical centers. Recurrent GISTs were excluded. Pathology reports were cross-referenced to cases reported by each cancer registry. Risk for metastasis/death was determined according to National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: Forty-nine cases of non-recurrent GIST were identified. Only 19/49 (38.8%) cases were reported. None of the 30 non-reported cases were labeled malignant/metastatic on final pathology. To illustrate malignant potential, these tumors were risk stratified. Most (60%) of the non-reported cases were low risk, but there were 4 (13.3%) cases each in the intermediate, high, and unknown risk groups. Additionally, 7/30 (23.0%) cases were treated with tyrosine kinase inhibitors, highlighting clinical concern of malignant GIST. CONCLUSIONS: Our results show that nearly two thirds of GIST cases have been underreported, suggesting that current reporting practices underestimate its true incidence. Revision of reporting guidelines may result in a more accurate estimation of the US disease burden of GIST.

Melanoma, version 4.2014.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

A shortened activated partial thromboplastin time predicts the risk of catheter-associated venous thrombosis in cancer patients.

INTRODUCTION: Hypercoagulability due to high coagulation factor levels resulting from host inflammatory response to cancer contributes to an increased risk of venous thromboembolism (VTE) in cancer patients. Central venous catheters (CVCs) further heighten this risk. Activated partial thromboplastin time (aPTT) can be used to broadly screen for elevated levels of relevant coagulation factors. Our objective was to determine if a shortened aPTT ratio (coagulation time of test- to- reference plasma) was a predictor of CVC-associated VTE in cancer patients. MATERIALS AND METHODS: We performed a retrospective case-control study on cancer patients undergoing tunneled CVC insertion at our center from 1999 to 2006 and identified 40 patients who had CVC-associated VTE. VTE was confirmed with color duplex ultrasonography or computed tomography scan. For each case, we obtained 5 controls that had the same cancer diagnosis and were matched on the following factors: age, chemotherapy, hormone therapy (if applicable), tobacco use, TNM staging and year of diagnosis. All patients had aPTT testing within 30 days prior to surgery. We compared aPTT and aPTT ratio between cases and controls using Wilcoxon two sample test. RESULTS: aPTT ratio was significantly shorter in patients with CVC-related VTE as compared to controls [0.86 (95% confidence interval (CI) 0.78, 0.94) vs. 0.98 (0.94, 1.01), p=0.0003]. Mean aPTT was also significantly shorter. [25.6 seconds (95% CI 23.2, 27.9) vs. 28.1 (26.9, 29.3), p=0.001] aPTT ratios of the controls tended to spread across larger aPTT ratio values whereas those of cases tended to clustered around the mean. CONCLUSIONS: Cancer patients undergoing catheter placement who develop CVC-associated VTE have a shorter aPTT and aPTT ratio than those who do not develop VTE. aPTT, a simple and inexpensive test might be useful as a predictor of CVC-associated VTE risk in cancer patients.

Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart.

Rare cases of Merkel cell carcinoma have been encountered in lymph nodes with unknown extranodal primary, which exhibit similar morphologic and immunophenotypic features to those in primary cutaneous Merkel cell carcinomas. However, it is uncertain whether the nodal Merkel cell carcinoma is a primary tumor of the lymph node or represents a metastasis from an occult or regressed extranodal lesion. To establish an accurate diagnosis of the nodal Merkel cell carcinoma can be challenging because of significant morphologic mimics, including lymphoblastic lymphoma and metastatic small cell carcinoma. Moreover, there is no consensus for a diagnostic term, and many different terms have been used, which can be confusing and may not fully reflect the nature of nodal Merkel cell carcinoma. In this study, we investigated the detailed clinicopathologic features of 22 nodal Merkel cell carcinomas, with comparison to 763 primary cutaneous cases retrieved from the literature. Overall, the nodal and cutaneous Merkel cell carcinomas shared similar clinical presentations, morphologic spectrum, and immunophenotype; both were mostly seen in elderly male with a typical neuroendocrine morphology. Most of cases expressed CK20, synaptophysin, and chromogranin A; and PAX5 and TdT were also positive in majority of cases. However, nodal Merkel cell carcinomas had a significantly lower association with Merkel cell polyomavirus than cutaneous cases (31% vs 76%, P=0.001). Therefore, these two entities may arise from overlapping but not identical biological pathways. We also recommend the use of the diagnostic term 'Merkel cell carcinoma of lymph node' to replace many other names used.

Melanoma, version 2.2013: featured updates to the NCCN guidelines.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.

BACKGROUND: Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database. METHODS: Seventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed. RESULTS: Of 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN. CONCLUSIONS: These results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.

Differential expression patterns of capping protein, protein phosphatase 1, and casein kinase 1 may serve as diagnostic markers for malignant melanoma.

Early and accurate diagnosis of malignant melanoma is critical for patient survival. However, currently used diagnostic markers are insufficiently specific, which limits their utility. We aimed to identify molecular markers that are more specific to malignant melanoma, thereby aiding in melanoma diagnosis and treatment. A PCR-based suppression subtractive hybridization was used to identify capping protein Z-line α1, protein phosphatase 1 catalytic subunit ß isoform (PP1CB), and casein kinase 1 α1 (CSNK1A1) as being differentially expressed between melanoma cells and normal melanocytes. Quantitative reverse transcription-PCR and western blot analysis confirmed that these genes were overexpressed in melanoma cells. In addition, immunohistochemical assays revealed that the expression of PP1CB and CSNK1A1 was significantly greater in human melanoma specimens than nevi (P<0.0001). Combined application of PP1CB and CSNK1A showed high sensitivity and specificity for melanoma. Thus, our data suggest that PP1CB and CSNK1A1 are potential biomarkers for distinguishing malignant melanoma from other melanocytic lesions. In addition, because capping protein Z-line α1, PP1CB, and CSNK1A1 are involved in cell motility, which underlies invasion and metastasis of human cancer; they may be novel targets for antimetastatic therapies as well.

Minimally invasive total gastrectomy for gastric cancer: a pilot series.

BACKGROUND: Minimally invasive surgery for select gastrointestinal disease has gained worldwide acceptance. However, laparoscopic total gastrectomy for cancer remains controversial. The purpose of this study was to examine an initial experience with laparoscopic total gastrectomy. METHODS: Medical records of 16 consecutive patients who underwent laparoscopic total gastrectomy between September 2007 and December 2009 were reviewed in a retrospective manner. Esophagojejunostomy was completed using a transorally delivered anvil, with double-stapled esophageal anastomosis. RESULTS: There were no conversions to open procedures. Two patients (12.5%) required extended resections with en bloc distal pancreatectomy and splenectomy, one of whom also underwent transverse colectomy. The median lymph node count for patients who underwent D2 lymphadenectomy (n = 12) for gastric adenocarcinoma was 31. There were no perioperative deaths and the median length of stay was 8 days. There were no anastomotic leaks, but three patients developed anastomotic strictures amenable to dilatation. CONCLUSIONS: Minimally invasive total gastrectomy can be performed safely and with adequate lymphadenectomy. The procedure provides an excellent short-term outcome with potential for improved patient outcome.

Prediction of the adequacy of lymph node retrieval in colon cancer by hospital type.

BACKGROUND: Examination of 12 or more regional lymph nodes (LNs) is the accepted minimum for nodal staging in colon cancer and serves as a surrogate for adequate resection. OBJECTIVE: To determine the contributing role of the hospital in the number of LNs retrieved. Design/ SETTING: We retrospectively reviewed colon resections in 83 patients by 2 surgical oncologists at a National Comprehensive Cancer Network (NCCN) hospital or at community-based hospitals from January 1, 2002, through December 31, 2007. PATIENTS: We included all patients undergoing colectomy for primary colon cancer and excluded patients with recurrence, rectal cancer, or preoperative chemotherapy. MAIN OUTCOME MEASURES: Total number of LNs retrieved. We also analyzed clinical factors accounting for differences. RESULTS: The median number of LNs examined at the NCCN hospital (42 patients) vs the community hospitals (41 patients) were 17.8 vs 7.0 (P < .001), and the frequency of an inadequate number of LNs examined (<12) was 11 of 42 cases (26%) vs 35 of 41 cases (85%) (P < .001). Potential predictive factors for LNs retrieved were grouped into modifiable (hospital type, surgeon, and surgical approach [laparoscopic vs open]) and nonmodifiable (age, sex, and tumor location). On multivariate analysis of the factors, hospital type was the only modifiable factor predictive of LNs reported (P < .001). CONCLUSIONS: Our study is the first, to our knowledge, to demonstrate that the number of LNs removed in colectomies performed by the same 2 surgeons depends on the hospital type (NCCN vs community) in which the resection occurred. We postulate that the number of LNs retrieved may be related to the institution's pathological review in addition to the extent of surgical resection.

Increased incidence of pancreatic fistulas after the introduction of a bioabsorbable staple line reinforcement in distal pancreatic resections.

Pancreatic fistula is a major cause of morbidity after distal pancreatic resection. When resections are performed with linear stapling devices, the use of bioabsorbable staple line reinforcement has been suggested to decrease the rate of pancreatic fistula. Our objective was to investigate the incidence of pancreatic fistula when using the Gore Seamguard staple line reinforcement in stapled distal pancreatic resections. A retrospective review of 30 consecutive patients with stapled distal pancreatectomy was conducted. A broad definition of pancreatic fistula was used. Clinicopathologic factors and outcomes were compared between groups. Pancreatic fistula was diagnosed in 11 of 15 patients (73%) and three of 15 patients (20%) in the Seamguard and non-Seamguard groups, respectively (P = 0.002). Pancreatic parenchymal transection at the neck of the gland was associated with pancreatic fistula, whereas laparoscopic procedures, splenic preservation, or additional organ resection were not. On multivariate analysis, the association between Seamguard use and pancreatic fistula was significant (P = 0.005). In conclusion, after introduction of the Gore Seamguard bioabsorbable staple line reinforcement, we experienced a significant increase in the rate of pancreatic fistula. This experience raises concern about the efficacy of this device in limiting pancreatic fistula after stapled distal pancreatic resection.

Totally laparoscopic gastric resection with extended lymphadenectomy for gastric adenocarcinoma.

BACKGROUND: Laparoscopic gastric resection with extended lymphadenectomy is being evaluated in North America for the surgical treatment of gastric cancer. The aim of this study is to compare short-term postoperative and oncologic outcomes of laparoscopic and open resection for gastric cancer at a single cancer center. METHODS: The study population consisted of patients with gastric adenocarcinoma who underwent a completely abdominal intervention with curative intent. Laparoscopic and open gastric resections were compared. A totally laparoscopic technique was employed with a robotic extended lymphadenectomy in a subset of patients. RESULTS: A total of 78 consecutive patients were evaluated, including 30 laparoscopic and 48 open procedures. An extended lymphadenectomy was performed in 58 patients and was executed robotically in 16 of these. There was no difference in the mean number of lymph nodes retrieved by laparoscopic or open approach (24 +/- 8 vs. 26 +/- 15, P = .66). Laparoscopic procedures were associated with decreased blood loss (200 vs. 383 mL, P = .0009) and length of stay (7 vs. 10 days, P = .0009), but increased operative time (399 vs. 298 minutes, P < .0001). CONCLUSION: Completely laparoscopic gastric resection yields similar lymph node numbers compared with open surgery for gastric cancer. It was found to be advantageous in terms of operative blood loss and length of stay. Minimally invasive techniques represent an oncologically adequate alternative for the surgical treatment of gastric adenocarcinoma.