Tumor-positive resection margins reflect an aggressive tumor biology in pancreatic cancer.

BACKGROUND: Resection margin status has been shown to impact outcomes for pancreatic adenocarcinoma (PAC), yet it remains unknown whether margin status is a reflection of tumor biology or surgical technique. METHODS: Two hundred eighty-three consecutive patients with pancreatic adenocarcinoma were identified in a prospectively maintained database. Only patients with R0 (n = 207) or R1 (n = 76) tumors were included. Each operative surgeon's first 50 cases were excluded to control for technical inexperience. Univariable and multivariable analyses of clinicopathologic and intra-operative factors were performed. RESULTS: The median follow-up for the cohort was 30.3 months with a median overall survival (OS) of 19.0 months. The R1 group had a higher rate of lymph node ratio >0.2 (41% vs. 25%; P = 0.013), and more microvascular invasion (64% vs. 44%; P = 0.007). R0 resections had both improved overall survival (22.7 months vs. 15.0 months, P = 0.004) and disease free survival (13.5 months vs. 10.7 months, P = 0.026). Factors independently associated with overall survival were microvascular invasion (HR 2.26; P = 0.001), pre-existing pulmonary disease (HR 2.18, P = 0.043), and cardiac disease (HR 1.78, P = 0.033). CONCLUSION: Factors associated with an R1 resection reflect a biologically more aggressive tumor, with a higher likelihood of microvascular invasion and increased positive lymph node ratio.

Impact of post-operative complications on quality of life after pancreatectomy.

CONTEXT: Pancreatectomies for malignant and benign diseases are increasingly being performed worldwide. Recent studies, that have evaluated quality of life in pancreatectomy, have reported conflicting outcomes. OBJECTIVE: This study was undertaken to analyze the quality of life changes reported by patients with pancreatic cancer undergoing pancreatectomy. DESIGN: Post-hoc analysis was performed of a clinical trial examining the safety of intraoperative autotransfusion during oncologic resections. MAIN OUTCOME MEASURES: Perioperative (90-day) complications were graded prospectively using a validated 5-point scale. Quality of life parameters were recorded prospectively by a single trained interviewer preoperatively, at the first post-operative outpatient visit, and at 6 weeks, 3 months, and 6 months follow-up using the EORTC QLQ-C30 and FACT-An instruments. RESULTS: Pancreatectomy for adenocarcinoma was performed in 34 patients with a median follow-up of 2 years (range: 1-1.5 years). Major (grade≥3) complications occurred in 12 (35.3%) of patients. Early (<6 month) recurrence was noted in 2 patients (5.9%). Increased severity of fatigue, pain, dyspnea, and loss of appetite over baseline were noted at initial follow-up (P<0.05); however, symptom scores normalized at 6-week follow-up, and remained stable at 6 months. No significant difference was noted in quality of life metrics between patients with or without major complications (P>0.11). A significant (P=0.023) decline in cognitive function vs. baseline was noted at 6-month follow-up after pancreatectomy. Using a repeated-measures generalized linear model, neither age, nor complication occurrence, nor adjuvant therapy, nor early recurrence accounted for this cognitive decline (P>0.10). CONCLUSION: Quality of life metrics tend to normalize to preoperative levels after pancreatectomy at 6 weeks post-operatively. The occurrence of major complications does not predict a decreased quality of life. The decrease in self-reported cognitive function at six months in this cohort merits further study.

The role of FDG-PET-CT is limited in initial staging of nodal metastasis for thin cutaneous melanoma.

INTRODUCTION: Positron emission tomography computed tomography (PET-CT) is often used to stage nodal metastases in thin cutaneous melanoma, with limited evidence. METHODS: A retrospective review of patients with cutaneous malignant melanoma treated at our institution was performed from 2005 to 2015, identifying those who received a PET-CT prior to lymphadenectomy. Biopsy features, lymph node status, and PET-CT results were collected. We calculated the overall sensitivity, specificity, accuracy, likelihood ratios, and positive predictive value of PET-CT in identifying nodal metastases. Results were stratified by initial biopsy tumor depth. RESULTS: We identified 367 cases; 95 obtained a PET-CT prior to lymphadenectomy. Overall, sensitivity and specificity of PET-CT was 34.6% and 95.4%, respectively. The positive likelihood ratio and negative likelihood ratio were 7.62 and 0.68, respectively. The accuracy was 78.2%. The positive predictive value for T3 and T4 melanomas were 100% and 81.4%, respectively. For thin melanomas, specificity and accuracy was 88.2% and 88.2%, respectively. CONCLUSIONS: PET-CT has low specificity and its use alone is not recommended for initial staging of nodal metastases in thin cutaneous malignant melanoma.

Comparing treatment patterns of hepatocellular carcinoma at academic centers and non-academic centers within the Mountain Region.

BACKGROUND: Our objective is to explore differences in survival and treatment approaches for hepatocellular carcinoma (HCC) between academic centers (ACs) and non-academic centers (NACs), which may contribute to disparities in the Mountain Region (MR). METHODS: Using the National Cancer Database, HCC cases from 2004 to 2015 in the MR were divided into AC and NAC subgroups. Cox-proportional hazard regression and binary logistic regression were performed to analyze survival, compare treatment patterns, and examine the effect of facility type and surgical approach on margin status. RESULTS: Treatment at ACs, compared to NACs, is associated with improved survival. At ACs, the odds of surgical or systemic treatment were higher. The odds of receiving radiation and positive margins was lower. Overall, the odds of positive margins was higher with laparoscopic compared to open or an unspecified surgical approach; this relationship persisted on subgroup analysis of NACs, but not ACs. CONCLUSIONS: Treatment of HCC at an AC in the MR increases the odds of surgery and improves survival. A laparoscopic approach increases the odds of positive margins, irrespective of center type.

Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model.

Irreversible electroporation (IRE) is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation) modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6), 7 (n = 6), 14 (n = 6), 21 (n = 6), 30 (n = 8), and 60 (n = 8) days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm(3) ± 884). Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals) were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001). Recurrent tumors were also significantly larger (mean 4,578 mm(3) ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001). Recurrent tumors had a steeper growth curve (slope = 0.73) compared with primary tumors (0.60, P = 0.02). Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being considered.

Necrotizing soft tissue infections: improved outcomes with modern care.

The outcome of necrotizing soft tissue infections (NSTI) remains unchanged despite advances in care. Reasons cited are changing patterns of causative factors, delays in diagnosis, and inadequate antibiotic coverage and surgical treatment. To document outcomes of NSTI after aggressive management and to identify risk factors of mortality and prolonged hospital stay, we reviewed all our patients with NSTI admitted from January 2000 to January 2002. Causative factors, comorbid conditions, site of NSTI, physiologic parameters, symptoms, diagnostic tests, therapeutic interventions, and outcomes were analyzed. Patients were treated aggressively with antibiotics, admission to ICU, and frequent surgical debridements. Of 46 patients identified, 28 (61%) were admitted in ICU, and eight (17%) died. The patients who died had higher admission white blood cell counts (46 +/- 22 vs 22 +/- 10 x 10(3)/mm3, P = 0.01), higher admission pain score (8 +/- 1 vs 5 +/- 3, P = 0.02), longer intervals from admission to antibiotic administration (16 +/- 20 vs 6 +/- 12 hours, P = 0.02), and fewer surgical debridements (2.6 +/- 1.1 vs 3.6 +/- 1.7, P = 0.04). No independent risk factors of mortality or ICU admission were identified. We concluded that severe local pain and a significantly elevated white blood cell count on admission should alert the physician to the presence of severe infection and prompt the initiation of expeditious aggressive treatment.

Necrotizing soft-tissue infections.

It has been more than 130 years since NSTIs were first described. Despite the development of various classification systems and progress in surgical management, these infections continue to have high mortality and pose enormous diagnostic and therapeutic challenges. For optimal outcome, treatment involves rapid institution of appropriate antibiotic coverage and early wide surgical debridement. Recovery requires aggressive resuscitation, postoperative nutritional support and wound care that is similar to the care of burn patients in many respects. The entire therapeutic process requires a well-prepared and coordinated team of health care professionals including EPs, general, orthopedic, and other specialist surgeons, infectious disease consultants, specially trained nursing staff, and physical therapists.

Health-related quality of life changes following major and minor hepatic resection: the impact of complications and postoperative anemia.

BACKGROUND: Few studies have evaluated the health-related quality-of-life (QOL) changes in patients following major liver resection for malignancy. METHODS: QOL parameters were recorded prospectively at baseline (preoperative), and through 6 months of follow-up using various instruments. RESULTS: Major complications occurred in 10 of 41 patients. At the initial outpatient visit, patients reported decreased global QOL with increased fatigue compared with baseline, which normalized at 6 weeks' follow-up and remained stable at 6 months. Those with major complications reported increased severity of pain over baseline at initial follow-up and at 6 months. Patients anemic at the time of discharge had worse physical QOL at 6 weeks, but levels similar to nonanemic patients at 3 months. CONCLUSIONS: Major complications are associated with increased reporting of pain persisting at 6 months. Attention to pain control, especially among patients with major complications, may improve QOL after major hepatic resection.

Negative effects of transfused blood components after hepatectomy for metastatic colorectal cancer.

There has been conflicting evidence regarding negative effects of blood transfusion in oncology patients. This study was undertaken to determine any negative effects of specific blood product transfusion after resection of hepatic colorectal metastases (CRM). Retrospective review of patients undergoing hepatectomy for CRM from 1995 to 2009 at a single institution was performed. Specific attention was paid to the effect of blood transfusion within 30 days of operation on overall survival, disease-free survival (DFS), and complications. To mitigate the bias introduced by complications that require blood transfusion to treat, only nonbleeding complications were considered. Complications were analyzed with univariate and multivariate logistic regression. Survival was analyzed according to Kaplan-Meier and Cox proportional hazards. There were 239 patients included in the study. There were 64 (26.8%) receiving a transfusion of any kind with 25.5 per cent getting red cells (PRBCs), 7.11 per cent getting fresh-frozen plasma, and 3.77 per cent getting platelets. Multivariate analysis revealed only PRBC transfusion to be independently associated with nonbleeding complications (odds ratio, 1.980; 95% confidence interval, 1.094 to 3.582; P = 0.0239). There was no significant adverse effect of transfusion with any product on overall or DFS. PRBC transfusion appears to increase the risk of postoperative complications; thus, strategies to minimize blood use may be warranted.

Impact of histology on survival in retroperitoneal sarcomas.

BACKGROUND: The current American Joint Committee on Cancer AJCC staging system applies to all soft-tissue sarcomas and does not allow for consideration of many features unique to retroperitoneal sarcomas (RPSs). The aim of this study was to analyze factors predictive of recurrence and survival for patients with resected RPSs. METHODS: This was a retrospective analysis of consecutive patients with primary RPS who underwent resection. A 3-tiered histological classification was examined: atypical lipomatous tumors (ALTs), non-ALT liposarcomas (LPSs), and other. Univariate and multivariate analyses were used to identify factors associated with differences in disease-free survival (DFS) and overall survival (OS) among groups. RESULTS: Sixty RPS patients were analyzed: 16 patients (27%) had ALTs, 7 patients (12%) had LPSs, and 37 patients (62%) had other histologies. A comparison of the 3 groups showed a significant difference in OS among groups (P < .017). High-grade tumors favored shorter DFS (P = .06) but were not associated with decreased OS when compared with low-grade tumors (P = .86). CONCLUSIONS: These findings support an alternative staging system for RPS, inclusive of histology, which may prove useful in operative planning and prognostication.

Lymphovascular invasion as a prognostic factor in melanoma.

The prognostic significance of lymphovascular invasion (LVI) in melanoma remains controversial. Clinicopathologic data from a prospective trial of patients with melanoma were analyzed with respect to LVI. Disease-free survival and overall survival (OS) were evaluated by Kaplan-Meier (KM) analysis. Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive sentinel nodes (SLN) and survival. A total of 2183 patients were included in this analysis; 171 (7.8%) had LVI. Median follow-up was 68 months. Factors associated with LVI included tumor thickness, ulceration, and histologic subtype (P < 0.05). LVI was associated with a greater risk of SLN metastasis (P < 0.05). By KM analysis, LVI was associated with worse OS (P = 0.0009). On multivariate analysis, age, gender, thickness, ulceration, anatomic location, and SLN status were predictors of OS; however, LVI was not an independent predictor of OS. Among patients with regression, the 5-year OS rate was 49.4 per cent for patients with LVI versus 81.1 per cent for those with no LVI (P < 0.0001). LVI is associated with a greater risk of SLN metastasis. Although LVI is not an independent predictor of OS in general, it is a powerful predictor of worse OS among patients who have evidence of regression of the primary tumor.