Nicotinamide phosphoribosyltransferase expression and clinical outcome of resected stage I/II pancreatic ductal adenocarcinoma.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) plays a key role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), which is a vital cofactor in redox reactions and a substrate for NAD+ consuming enzymes including CD38, PARPs and sirtuins. NAMPT over-expression has been shown in various cancers and its inhibition decreases cancer cell growth, making it an attractive therapeutic target. Here we examine the NAMPT expression in a large cohort of resected stage I/II pancreatic ductal adenocarcinomas (PDAs) and correlate its expression with clinical outcomes and pathologic features. METHODS: A retrospective review of patients with PDAs was conducted at a single institution. Tissue microarrays (TMAs) containing primary PDAs and their metastatic lymph nodes (mLNs) were constructed and stained for NAMPT expression. Each TMA core was evaluated for staining intensity of cancer cells (0 = no staining, 1+ = weak, 2+ = moderate, 3+ = strong) and a mean score was calculated for each case with at least two evaluable cores. NAMPT expression was correlated with clinicopathological variables using chi-squared or Fisher's exact test, and t-tests for categorical and continuous variables, respectively. Survival probabilities were estimated and plotted using the Kaplan-Meier method. Cox proportional hazards regression was used to assess the effects of NAMPT staining values on recurrence-free survival (RFS) and overall survival (OS). This study was conducted under an approved IRB protocol. RESULTS: 173 primary PDAs had at least 2 TMA cores with identifiable cancer cells. The mean IHC score was 0.55 (range: 0 to 2.33). The mean IHC score of mLNs was 0.39 (range: 0-2), which was not significantly different from their primary tumors (mean IHC score = 0.47, P = 0.38). Sixty-four percent (111/173) of PDAs were positive for NAMPT staining. Stage II tumors were more likely to be positive (68% of 151 vs 41% of 22; P = 0.01). Non-obese non-diabetic patients were more likely to have NAMPT+ tumors (43.7% vs. 27.9%, P = 0.04). While RFS and OS were not statistically different between NAMPT+ vs. NAMPT- PDAs, patients with NAMPT- tumors tended to have a longer median OS (26.0 vs. 20.4 months, P = 0.34). CONCLUSION: NAMPT expression was detected in 64% of stage I/II PDAs and up to 72% in non-obese non-diabetic patients. Frequency of NAMPT expression correlated with pathological stage, consistent with published literature regarding its role in cancer progression. While RFS and OS were not statistically significantly different, patients with NAMPT+ PDAs tended to have a shorter survival. Thus, NAMPT inhibition may prove beneficial in clinical trials.

Pharmacological Ascorbate as an Adjuvant for Enhancing Radiation-Chemotherapy Responses in Gastric Adenocarcinoma.

Gastric adenocarcinoma most often presents at an advanced stage and overall five-year survival of ∼30%. Pharmacological ascorbate (high-dose IV ascorbate) has been proposed as a promising nontoxic adjuvant to standard radio-chemotherapies in several cancer types. In the current study, pharmacological ascorbate (0.5-2 m M) caused a dose-dependent decrease (70-85% at 2 m M) in clonogenic survival of gastric adenocarcinoma cells (AGS and MNK-45), but was relatively nontoxic to a small intestinal epithelial nonimmortalized human cell isolate (FHs 74 Int). The addition of pharmacological ascorbate (1 m M) to standard radio-chemotherapies [i.e., 5-FU (5 µ M); cisplatin (0.5 µ M); irinotecan (2.5 µ M); carboplatin (5 µ M); paclitaxel (2-4 n M); and X rays (1.8 Gy)] also potentiated gastric cancer clonogenic cell killing [additional decreases were noted with: ascorbate plus 5-FU/radiation (1%); ascorbate plus cisplatin/irinotecan (9-19%); and ascorbate plus paclitaxel/carboplatin (6-7%)]. The gastric cancer cell toxicity and chemosensitization seen with pharmacological ascorbate was dependent on H2O2 and the presence of catalytic metal ions. In addition, pharmacological ascorbate dosing resulted in a concentration-dependent decrease (64% at 20 m M, P ≤ 0.0001) in cancer cell invasion and migration that was inhibited by catalase. Finally, pharmacological ascorbate significantly increased the overall survival of mice with gastric cancer xenografts when used in combination with paclitaxel, carboplatin and radiation ( P = 0.019). These results demonstrate that pharmacological ascorbate is selectively cytotoxic to gastric adenocarcinoma cells (relative to normal intestinal epithelial cells) by a mechanism involving H2O2 and redox active metal ions. Furthermore, pharmacological ascorbate significantly enhances gastric cancer xenograft responses to radio-chemotherapy as well as inhibiting tumor cell migration and invasiveness. Overall, these results support the hypothesis that pharmacological ascorbate can be used as an adjuvant with standard-of-care radio-chemotherapies for the treatment of gastric adenocarcinomas.

The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature.

Sarcopenia is the subclinical loss of skeletal muscle and strength and has been extensively studied in both the cancer and surgical literature. Specifically, sarcopenia has gained significant recognition as an important prognostic factor for both complications and survival in cancer patients. Herein, we review the current literature to date highlighting the specific impact of sarcopenia in patients undergoing oncologic procedures.

Disruption of thioredoxin metabolism enhances the toxicity of transforming growth factor ß-activated kinase 1 (TAK1) inhibition in KRAS-mutated colon cancer cells.

Transforming growth factor ß-activated kinase 1 (TAK1) is critical for survival of many KRAS mutated colorectal cancer cells, and TAK1 inhibition with 5Z-7-oxozeaenol has been associated with oxidative stress leading to tumor cell killing. When SW 620 and HCT 116 human colon cancer cells were treated with 5µM 5Z-7-oxozeaenol, cell viability, growth, and clonogenic survival were significantly decreased. Consistent with TAK1 inhibition being causally related to thiol-mediated oxidative stress, 10mM N-acetylcysteine (NAC) partially reversed the growth inhibitory effects of 5Z-7-oxozeaenol. In addition, 5Z-7-oxozeaenol also increased steady-state levels of H2DCFDA oxidation as well as increased levels of total glutathione (GSH) and glutathione disulfide (GSSG). Interestingly, depletion of GSH using buthionine sulfoximine did not significantly potentiate 5Z-7-oxozeaenol toxicity in either cell line. In contrast, pre-treatment of cells with auranofin (Au) to inhibit thioredoxin reductase activity significantly increased levels of oxidized thioredoxin as well as sensitized cells to 5Z-7-oxozeaenol-induced growth inhibition and clonogenic cell killing. These results were confirmed in SW 620 murine xenografts, where treatment with 5Z-7-oxozeaenol or with Au plus 5Z-7-oxozeaenol significantly inhibited growth, with Au plus 5Z-7-oxozeaenol trending toward greater growth inhibition compared to 5Z-7-oxozeaenol alone. These results support the hypothesis that thiol-mediated oxidative stress is causally related to TAK1-induced colon cancer cell killing. In addition, these results support the hypothesis that thioredoxin metabolism is a critical target for enhancing colon cancer cell killing via TAK1 inhibition and could represent an effective therapeutic strategy in patients with these highly resistant tumors.

Sarcopenia is an independent predictor of complications following pancreatectomy for adenocarcinoma.

BACKGROUND AND OBJECTIVES: Sarcopenia, which is subclinical loss of skeletal muscle mass, is commonly observed in patients with malignancy. The objective of this study is to determine the correlation between sarcopenia and operative complications following pancreatectomy for cancer. METHODS: A retrospective review of a pancreatectomy database was performed. The Hounsfield Unit Average Calculation (HUAC) of the psoas muscle, a marker of muscle density and fatty infiltration, was measured from preoperative CT scans. Complications were graded and multivariate logistic regression analysis was performed. RESULTS: One hundred eighteen patients met criteria for analysis; the overall morbidity rate was 78.8% (n = 93). There were 31 (26.3%) patients who met criteria for sarcopenia using the HUAC. When analyzed as a continuous variable, sarcopenia was an independent predictor of major grade III complications, length of stay, intensive care unit admission, delayed gastric emptying, and infectious, gastrointestinal, pulmonary, and cardiac complications. CONCLUSIONS: These data suggest that sarcopenia as measured with the HUAC, a value that can be obtained from a preoperative CT scan, is a significant independent predictor of surgical outcome and can be used to improve patient selection and informed consent prior to pancreatectomy in patients with cancer.

Loss of SOD3 (EcSOD) Expression Promotes an Aggressive Phenotype in Human Pancreatic Ductal Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDA) cells are known to produce excessive amounts of reactive oxygen species (ROS), particularly superoxide, which may contribute to the aggressive and refractory nature of this disease. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide in the extracellular environment. This study tests the hypothesis that EcSOD modulates PDA growth and invasion by modifying the redox balance in PDA. EXPERIMENTAL DESIGN: We evaluated the prognostic significance of EcSOD in a human tissue microarray (TMA) of patients with PDA. EcSOD overexpression was performed in PDA cell lines and animal models of disease. The impact of EcSOD on PDA cell lines was evaluated with Matrigel invasion in combination with a superoxide-specific SOD mimic and a nitric oxide synthase (NOS) inhibitor to determine the mechanism of action of EcSOD in PDA. RESULTS: Loss of EcSOD expression is a common event in PDA, which correlated with worse disease biology. Overexpression of EcSOD in PDA cell lines resulted in decreased invasiveness that appeared to be related to reactions of superoxide with nitric oxide. Pancreatic cancer xenografts overexpressing EcSOD also demonstrated slower growth and peritoneal metastasis. Overexpression of EcSOD or treatment with a superoxide-specific SOD mimic caused significant decreases in PDA cell invasive capacity. CONCLUSIONS: These results support the hypothesis that loss of EcSOD leads to increased reactions of superoxide with nitric oxide, which contributes to the invasive phenotype. These results allow for the speculation that superoxide dismutase mimetics might inhibit PDA progression in human clinical disease.

Minimally invasive pancreatectomy for cancer: a critical review of the current literature.

Minimally invasive surgery (MIS) has transformed operative practices by offering patients procedures with reduced hospital stay and recovery compared to that of open operations. In spite of the advantages of a MIS approach, the application to pancreatectomy has only recently emerged. This review aims to analyze and discuss available comparative studies as they relate to resection techniques for treatment of malignant disease. A PubMed search was used to obtain original studies and meta-analyses relating to MIS pancreatectomy from 2008 to 2013. Several studies were identified that reported on the application of MIS specifically to the treatment of cancer, many of which were retrospective, single-institution studies. Notwithstanding an inherent selection bias, several studies suggest that MIS can provide equivalent R0 resection rates, number of lymph nodes harvested, and survival to that of open resection. Furthermore, parameters such as blood loss and length of stay are significantly reduced in patients treated with MIS. The current literature supports the conclusion that MIS is safe and effective as a treatment for cancer in well-selected patients in the hands of experienced surgeons. However, the published studies to date are observational in nature and therefore higher quality studies will be needed to support the application and generalizability of MIS in the treatment of pancreatic malignancies.

Pancreatectomy predicts improved survival for pancreatic adenocarcinoma: results of an instrumental variable analysis.

BACKGROUND AND OBJECTIVE: Pancreatic resection is the standard treatment option for patients with stage I/II pancreatic ductal adenocarcinoma (PDA), yet many studies demonstrate low rates of resection. The objective of this study was to evaluate whether increasing resection rates would result in an increase in average survival in patients with stage I/II PDA. METHODS: SEER (Surveillance, Epidemiology, and End Results) data were analyzed for patients with stage I/II pancreatic head cancers treated from 2004 to 2009. Pancreatectomy rates were examined within Health Service Areas (HSAs) across 18 SEER regions. An instrumental variable analysis was performed, using HSA rates as an instrument, to determine the impact of increasing resection rates on survival. RESULTS: Pancreatectomy was performed in 4322 of 8323 patients evaluated with stage I/II PDA (overall resection rate = 51.9%). The resection rate across HSAs ranged from an average of 38.6% (lowest quintile) to 67.3% (highest quintile). Median survival was improved in HSAs with higher resection rates. Instrumental variable analysis revealed that, for patients whose treatment choices were influenced by rates of resection in their geographic region, pancreatectomy was associated with a statistically significant increase in overall survival. CONCLUSIONS: When controlling for confounders using instrumental variable analysis, pancreatectomy is associated with a statistically significant increase in survival for patients with resectable PDA. On the basis of these results, if resection rates were to increase in select patients, then average survival would also be expected to increase. It is important that this information be provided to physicians and patients so that they can properly weigh the risks and advantages of pancreatectomy as treatment of PDA.

Morbidity and mortality following elective splenectomy for benign and malignant hematologic conditions: analysis of the American College of Surgeons National Surgical Quality Improvement Program data.

IMPORTANCE: Splenectomy is a commonly performed operation; however, data from large series regarding operative outcomes to help guide decision making and informed consent are lacking. OBJECTIVE: To evaluate clinical and pathologic variables associated with morbidity and mortality following elective splenectomy for benign and malignant hematologic conditions in the United States. DESIGN, SETTING, AND PARTICIPANTS: A review of the American College of Surgeons National Surgical Quality Improvement Program data for elective splenectomy between January 1, 2005, and December 31, 2011, was performed, and 1715 eligible individuals were identified. INTERVENTION: Elective splenectomy for hematologic conditions. MAIN OUTCOMES AND MEASURES: Complications and operative mortality were evaluated for the entire cohort and compared between patients with benign vs malignant diseases. Multivariable logistic regression was used to evaluate factors predictive of operative complications and death. RESULTS: Splenectomy was performed in 1344 patients (78.4%) for benign disease and in 371 patients (21.6%) for malignant disease. Two hundred ninety-one patients (17.0%) had a complication, and operative mortality occurred in 27 patients (mortality rate, 1.6%). Patients treated for malignant disease had a higher rate of overall complications (27.2%) compared with patients treated for benign disease (14.1%) (P < .001). Several variables were independent predictors of complications, including malignant disease (vs benign) (Odds Ratio [OR], 1.86; 95% CI, 1.23-2.80; P = .003), independent performance status (vs dependent) (OR, 0.33; 95% CI, 0.07-1.52; P = .02), and increasing albumin level (OR, 0.75; 95% CI, 0.66-0.86; P < .001). Increasing age (OR, 1.03; 95% CI, 1.00-1.06; P = .05) was an independent predictor of mortality while increasing albumin level (OR, 0.63; 95% CI, 0.46-0.86; P = .003) predicted lower risk of operative death. From these data, a patient older than 60 years with a low preoperative albumin level has a predicted probability for operative death as high as 10.0%. CONCLUSIONS AND RELEVANCE: Preoperative performance and nutritional status are significant risk factors for complications and mortality following elective splenectomy. Although operative mortality continues to decrease over time, specific preoperative variables may help with patient selection before elective splenectomy for certain patients.

The critical role of peritoneal cytology in the staging of gastric cancer: an evidence-based review.

Positive peritoneal cytology (Cyt+) is an important staging tool for patients with locally advanced gastric cancer. The objective of this review is to evaluate the current literature regarding cytology evaluation in patients with gastric cancer and to provide recommendations on the inclusion of this powerful prognosticator in patients with this disease. A literature search was performed for recent and pertinent studies evaluating peritoneal cytology in patients with gastric adenocarcinoma. Peritoneal cytology as the only evidence for M1 disease is present in up to 10% of patients with locally advanced gastric cancer; survival in the setting of Cyt+ is dismal when gastrectomy is the first line of therapy. Improved survival is associated with response to chemotherapy indicated by conversion to negative cytology, good performance status, and antral tumors. Highly select patients with Cyt+ treated with gastrectomy show improved survival in only some of the available studies. There are high quality studies that support the routine practice of peritoneal cytology evaluation in patients with locally advanced gastric cancer. The role of gastrectomy remains unclear in patients with Cyt+ and clinical trials are needed to define the best treatment option for this select group of patients.

An interactive Bayesian model for prediction of lymph node ratio and survival in pancreatic cancer patients.

BACKGROUND: Regional lymph node status has long been used as a dichotomous predictor of clinical outcomes in cancer patients. More recently, interest has turned to the prognostic utility of lymph node ratio (LNR), quantified as the proportion of positive nodes examined. However, statistical tools for the joint modeling of LNR and its effect on cancer survival are lacking. METHODS: Data were obtained from the NCI SEER cancer registry on 6400 patients diagnosed with pancreatic ductal adenocarcinoma from 2004 to 2010 and who underwent radical oncologic resection. A novel Bayesian statistical approach was developed and applied to model simultaneously patients' true, but unobservable, LNR statuses and overall survival. New web development tools were then employed to create an interactive web application for individualized patient prediction. RESULTS: Histologic grade and T and M stages were important predictors of LNR status. Significant predictors of survival included age, gender, marital status, grade, histology, T and M stages, tumor size, and radiation therapy. LNR was found to have a highly significant, non-linear effect on survival. Furthermore, predictive performance of the survival model compared favorably to those from studies with more homogeneous patients and individualized predictors. CONCLUSIONS: We provide a new approach and tool set for the prediction of LNR and survival that are generally applicable to a host of cancer types, including breast, colon, melanoma, and stomach. Our methods are illustrated with the development of a validated model and web applications for the prediction of survival in a large set of pancreatic cancer patients.

Complications and survival associated with operative procedures in patients with unresectable pancreatic head adenocarcinoma.

BACKGROUND: Unresectable tumors of the pancreatic head are encountered in up to 20% of patients taken for resection. The objective of this study was to evaluate the complications and outcome associated with palliative surgical procedures to help guide management decisions in these patients. METHODS: Patients with pancreatic head adenocarcinoma taken to the operating room with curative intent who did not undergo pancreatectomy were evaluated. RESULTS: From 1997 to 2013, 50 patients were explored and found be unresectable due to M1 disease (n = 27, 54.0%) or vascular invasion (n = 23, 46.0%). Among unresectable patients, 34 (68.0%) had a palliative procedure performed including double bypass (n = 13), biliary bypass (n = 7), gastrojejunostomy (n = 5), or cholecystectomy (n = 9). Complications occurred in 22 patients (44.0%), and patients who had a palliative operation had a longer hospital stay and more major complications. Overall survival was reduced in patients treated with a palliative operation. CONCLUSIONS: Despite advancements in endoscopic palliation, operative bypasses are still commonplace in patients with unresectable pancreatic head cancer. In this study, patients treated with operative procedures had a high rate of complications without a notable improvement in outcome. These findings highlight the importance of identifying unresectable disease prior to surgery and support a selective approach to palliative operations.

A matched case-control study of IBD-associated colorectal cancer: IBD portends worse outcome.

BACKGROUND AND OBJECTIVES: The effect of inflammatory bowel disease (IBD) on outcome in patients with colorectal cancer (CRC) remains unclear. Our objective is to evaluate oncologic outcomes of patients with IBD-associated CRC. METHODS: We retrospectively reviewed a prospectively maintained database to identify patients with IBD-associated CRC. Clinicopathologic variables and overall survival were compared to patients with sporadic CRC using a 2:1 matched-controlled analysis. RESULTS: Fifty-five patients with IBD and CRC were identified. On univariate analysis, CRC patients with IBD had a significantly shorter median overall survival (68.2 months vs. 204.3 months, P = 0.01) compared to patients with sporadic CRC. On multivariate analysis, after adjusting for N and M stage, IBD was associated with an increased risk of death compared to sporadic CRC (HR = 2.011, 95% CI 1.24-3.23, P = 0.004). Stage 3 CRC patients with IBD in particular showed significantly decreased survival (23.0 vs. 133.9 months, P = 0.008). CONCLUSIONS: In this study, patients with node-positive IBD-associated CRC had a significant increased risk of death and a shorter overall survival than those with sporadic disease and may require tailored adjuvant therapy and surveillance protocols. Continued investigation to elucidate the mechanisms that contribute to these observations is justified.

Prolyl-4-hydroxylase 3 (PHD3) expression is downregulated during epithelial-to-mesenchymal transition.

Prolyl-4-hydroxylation by the intracellular prolyl-4-hydroxylase enzymes (PHD1-3) serves as a master regulator of environmental oxygen sensing. The activity of these enzymes is tightly tied to tumorigenesis, as they regulate cell metabolism and angiogenesis through their control of hypoxia-inducible factor (HIF) stability. PHD3 specifically, is gaining attention for its broad function and rapidly accumulating array of non-HIF target proteins. Data from several recent studies suggest a role for PHD3 in the regulation of cell morphology and cell migration. In this study, we aimed to investigate this role by closely examining the relationship between PHD3 expression and epithelial-to-mesenchymal transition (EMT); a transcriptional program that plays a major role in controlling cell morphology and migratory capacity. Using human pancreatic ductal adenocarcinoma (PDA) cell lines and Madin-Darby Canine Kidney (MDCK) cells, we examined the correlation between several markers of EMT and PHD3 expression. We demonstrated that loss of PHD3 expression in PDA cell lines is highly correlated with a mesenchymal-like morphology and an increase in cell migratory capacity. We also found that induction of EMT in MDCK cells resulted in the specific downregulation of PHD3, whereas the expression of the other HIF-PHD enzymes was not affected. The results of this study clearly support a model by which the basal expression and hypoxic induction of PHD3 is suppressed by the EMT transcriptional program. This may be a novel mechanism by which migratory or metastasizing cells alter signaling through specific pathways that are sensitive to regulation by O2. The identification of downstream pathways that are affected by the suppression of PHD3 expression during EMT may provide important insight into the crosstalk between O2 and the migratory and metastatic potential of tumor cells.

RABL6A Promotes Oxaliplatin Resistance in Tumor Cells and Is a New Marker of Survival for Resected Pancreatic Ductal Adenocarcinoma Patients.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic and predictive biomarkers are urgently needed to both stratify patients for clinical trials and select patients for adjuvant therapy regimens. This study sought to determine the biological significance of RABL6A (RAB, member RAS oncogene family-like protein 6 isoform A), a novel pancreatic protein, in PDAC. Analyses of RABL6A protein expression in PDAC specimens from 73 patients who underwent pancreatic resection showed that RABL6A levels are altered in 74% of tumors relative to adjacent benign ductal epithelium. Undetectable RABL6A expression, found in 7% (5/73) of patients, correlated with improved overall survival (range 41 to 118 months with 3/5 patients still living), while patients with RABL6A expression had a worse outcome (range 3.3 to 100 months, median survival 20.3 months) (P = 0.0134). In agreement with those findings, RABL6A expression was increased in pancreatic cancer cell lines compared to normal pancreatic epithelial cells, and its knockdown inhibited pancreatic cancer cell proliferation and induced apoptosis. Moreover, RABL6A depletion selectively sensitized cells to oxaliplatin-induced arrest and death. This work reveals that RABL6A promotes the proliferation, survival, and oxaliplatin resistance of PDAC cells, whereas its loss is associated with extended survival in patients with resected PDAC. Such data suggest RABL6A is a novel biomarker of PDAC and potential target for anticancer therapy.

Intraperitoneal drainage after pancreatic resection: a review of the evidence.

BACKGROUND: Despite a growing body of literature supporting the limited use of prophylactic intra-abdominal drainage for many procedures, drain placement after pancreatic resection remains commonplace and highly controversial. MATERIALS AND METHODS: Literature available in the PubMed was systematically reviewed by searching using combinations of keywords and citations in review articles regarding prophylactic drainage after pancreatic resection, early removal of intraoperatively placed drains after pancreatic resections, and risk factors and predictive tools for pancreatic fistula. RESULTS: Prospective randomized studies on prophylactic drainage after pancreaticoduodenectomy or distal pancreatectomy have not shown any benefit in decreasing pancreatic fistula, total complications, length of hospital stay, or readmission rates. Frequency of complications was significantly higher in patients receiving routine drainage. This was recently supported by retrospective studies; however, patients with risk factors for pancreatic fistula (soft pancreatic texture, prolonged operative times, and increased blood loss) were more likely to have prophylactic intra-abdominal drainage. Alternatively, if a drain is placed, prospective randomized studies demonstrate that early removal is safe in patients with postoperative day 1 drain amylase values <5000 U/L and associated with a lower rate of fistula. CONCLUSIONS: The current literature supports a strategy of selective drainage and early drain removal after pancreatic resection in low-risk patients.

A prognostic nomogram for prediction of recurrence in desmoid fibromatosis.

OBJECTIVE: To construct a postoperative nomogram to estimate the risk of local recurrence for patients with desmoid tumors. BACKGROUND: The standard management of desmoid tumors is resection, but many recur locally. Other options include observation or novel chemotherapeutics, but little guidance exists on selecting treatment. METHODS: Patients undergoing resection during 1982-2011 for primary or locally recurrent desmoids were identified from a single-institution prospective database. Cox regression analysis was used to assess risk factors and to create a recurrence nomogram, which was validated using an international, multi-institutional data set. RESULTS: Desmoids were treated surgically in 495 patients (median follow-up of 60 months). Of 439 patients undergoing complete gross resection, 100 (23%) had recurrence. Five-year local recurrence-free survival was 69%. Eight patients died of disease, all after R2 resection. Adjuvant radiation was not associated with improved local recurrence-free survival. In multivariate analysis, factors associated with recurrence were extremity location, young age, and large tumor size, but not margin. Abdominal wall tumors had the best outcome (5-year local recurrence-free survival rate of 91%). Age, site, and size were used to construct a nomogram with concordance index of 0.703 in internal validation and 0.659 in external validation. Integration of additional variables (R1 margin, sex, depth, and primary vs recurrent presentation) did not importantly improve concordance (internal concordance index of 0.707). CONCLUSIONS: A postoperative nomogram including only size, site, and age predicts local recurrence and can aid in counseling patients. Systemic therapies may be appropriate for young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions.

Prospective clinical trial of diagnostic peritoneal lavage to detect positive peritoneal cytology in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Positive peritoneal cytology equates M1 disease in patients with gastric cancer. Diagnostic peritoneal lavage (DPL) is a proven test to detect occult visceral injury in trauma patients. The objective of this study is to determine whether DPL can be used to assess peritoneal cytology in patients with gastric cancer. METHODS: Patients with gastric adenocarcinoma were prospectively enrolled to undergo DPL prior to diagnostic laparoscopy (DL). Saline was instilled through a percutaneous catheter and fluid was collected for cytology (DPL-cyt). Washings obtained during DL were used as controls (DL-cyt). RESULTS: DPL was successful in 22/27 patients (81.5%). Among the 22 successful DPLs, 12 had positive cytology (54.5%). Positive DPL-cyt specimens matched DL-cyt specimens in 12/12 cases (specificity = 100%). One of 10 cases with negative DPL-cyt was positive on the final DL-cyt (sensitivity = 92%). There were six patients with negative DPL-cyt who had visible M1 disease diagnosed with DL (DPL evaluation of M1 disease, sensitivity 54.5%, specificity = 100%). CONCLUSIONS: DPL is a safe method of detecting positive cytology in patients with gastric cancer, however gross M1 disease may be missed without visual inspection. The specific role of DPL in the staging workup of patients with gastric cancer remains to be determined.