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.

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.

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.

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.

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.

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 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.

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.

Management of complications following pancreatic resection: an evidence-based approach.

Despite significant improvements in operative mortality, morbidity remains a significant problem following pancreatectomy. Management of postpancreatectomy complications, namely pancreatic fistula, begins with a clear understanding of how these events are defined. There are now several unifying definitions for complications following pancreatectomy which have led to improved reporting of operative outcomes across institutions. Several randomized controlled trials have been performed in recent years that may lead to continued improvement in operative outcomes.

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.

Changes in the management of benign liver tumours: an analysis of 285 patients.

OBJECTIVES: Benign liver tumours (BLTs) are common and their management remains controversial. This study assesses the safety of a selective management approach. METHODS: Patients with BLT were identified from an institutional database. Patients with simple cysts or an incidental BLT in the setting of metastasis or concomitant malignancy were excluded. RESULTS: A total of 285 patients presenting during the period from January 1992 to December 2009 with haemangioma (53.0%), focal nodular hyperplasia (23.9%), adenoma (10.2%) or indeterminate/other lesions (13.0%) were evaluated. Of these, 117 patients (41.1%) underwent immediate resection and 168 patients (58.9%) were followed with serial imaging (median follow-up: 30 months). During observation, eight patients (4.8%) underwent resection for tumour growth, inability to exclude malignancy or symptoms; no patients demonstrated malignant transformation or tumour-related complications. During the study period, the number of BLTs evaluated and the proportion of patients observed increased from 129 BLTs of which 36.4% were observed in 1992-2002 to 156 BLTs of which 71.2% were observed in 2003-2009 (P < 0.001). Diagnostic uncertainty led to resection in 29.5% of patients during the earlier period, but in only 13.4% during the more recent 7 years (P < 0.05). CONCLUSIONS: Asymptomatic BLTs without concern for malignancy or adenoma can be safely observed with minimal risk for misdiagnosis. Patients selected for observation rarely require resection or develop tumour-related complications.

Whole-mount pathologic analysis of rectal cancer following neoadjuvant therapy: implications of margin status on long-term oncologic outcome.

OBJECTIVE: Extent of distal resection margins in rectal cancer surgery remains controversial. We set out to determine the long-term oncologic impact of resection margins in patients with locally advanced rectal cancer using a comprehensive pathologic whole-mount section analysis. BACKGROUND: It has been demonstrated that there is minimal disease beyond the gross tumor margin after neoadjuvant combined modality therapy (CMT) for rectal cancer. Although this suggests that close resection margins may be used for sphincter preservation, the long-term oncologic impact of this approach is unclear. METHODS: We prospectively enrolled 103 patients with locally advanced rectal cancer after neoadjuvant CMT. Whole-mount pathologic analysis was performed, and clinicopathologic variables were correlated with disease-specific survival (DSS). RESULT: : Sphincter preservation was achieved in 80% of patients, and the median distal margin was 2 cm (0.1 to 10 cm). There were 22 patients (21%) with distal margins 1 cm or less and no patient had a positive distal margin. Median radial margin was 1 cm and 4 patients (4%) had a margin of 1 mm or less. Viable distal intramural tumor spread was found in 3 patients (2.7%) and in all cases was limited to 1 cm or less from the gross tumor edge. At a median follow-up of 68 months, 5-year DSS was 86% and 1 patient experienced a local recurrence. Factors predictive of worse DSS included advanced tumor (T) and nodal (N) stage, tumor progression on neoadjuvant CMT, lack of a complete pathologic response, tumor location of 5 cm or less from the anal verge, and neurovascular invasion. The extent of the distal and radial margins of resection was not associated with DSS. CONCLUSIONS: These results suggest that carefully selected patients with locally advanced rectal cancers who undergo neoadjuvant CMT can achieve excellent local control and DSS with a sphincter-sparing rectal resection and a margin distal clearance of 1 cm.

Comparison of clinicopathologic factors in 122 patients with resected pancreatic and ileal neuroendocrine tumors from a single institution.

BACKGROUND: Recent population-based studies have demonstrated significant differences in outcome between patients with pancreatic and ileal neuroendocrine tumors. The objective of this study was to examine the clinicopathologic differences between ileal and pancreatic neuroendocrine tumors following resection. METHODS: A retrospective chart review was performed and data on clinicopathologic variables, biochemical markers, and follow-up of patients with resected ileal (INETs) and pancreatic (PNETs) neuroendocrine tumors were collected. The t test or analysis of variance (ANOVA) was used to compare means. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Between 1998 and 2010, 122 patients with PNETs and INETs were explored (70 PNETs and 52 INETs). Several variables were found to be significantly different between patients in both groups. INETs were more often associated with flushing (44 vs. 14%; P < 0.001) and diarrhea (63 vs. 16%; P < 0.001) and were more often associated with elevation in preoperative serum levels of pancreastatin (88 vs. 42%; P < 0.001), chromogranin A (78 vs. 54%; P = 0.036), and serotonin (90 vs. 43%; P < 0.001). INETs more frequently had vascular invasion on pathology (96 vs. 60%; P < 0.001), and presented more often with nodal and/or distant metastases (77 vs. 37%; P < 0.001). There was no significant difference in overall survival between patients in both groups. CONCLUSION: In this series, patients with INETs presented with a more advanced stage of disease compared with PNETs, had higher preoperative levels of 3 markers, and were more often symptomatic. Despite these factors, there was no significant difference in overall survival between patients with these 2 tumor types.

Incidence and management of gastrointestinal perforation from bevacizumab in advanced cancers.

Bevacizumab (Avastin™, Genentech) is a monoclonal antibody that deactivates the vascular endothelial growth factor leading to disruption of vital cancer signaling pathways and inhibition of angiogenesis which results in its anti-tumor activity. The use of bevacizumab in treating cancers has steadily increased since it was initially approved by the Food and Drug Administration for metastatic colorectal cancer. Clinical trials have revealed that bevacizumab has serious side effects, including spontaneous bowel perforation, which can occur in patients who have no involvement of the gastrointestinal tract by cancer. Although risk factors for bevacizumab-associated bowel perforation have been identified, it is still unclear which patients are specifically at risk for this complication. The management of bevacizumab-induced bowel perforation depends on the clinical presentation and the goals of care set by the treating physicians and the patient.

Treatment and outcome of patients with gastric remnant cancer after resection for peptic ulcer disease.

BACKGROUND: To study the pathology, treatment, and outcome of patients with gastric remnant cancer (GRC) after resection for peptic ulcer disease (PUD). METHODS: Review of a prospective gastric cancer database identified patients with GRC after gastrectomy for PUD. Clinicopathologic and treatment-related variables were obtained. Multivariate analysis was performed for factors associated with disease-specific survival (DSS). RESULTS: From January 1985 to April 2010, 4402 patients with gastric adenocarcinoma were treated at our institution and 105 patients (2.4%) had prior gastrectomy for PUD. Prior resections were most often Billroth II (N = 97, 92%). The median time from initial resection to development of GRC was 32 years (3-60 years), and the majority of tumors were located at the gastrointestinal anastomosis (N = 72, 69%). Median DSS was 1.3 years (0.6-2.1 years). Patients who had resection had a significantly better outcome than patients who did not have resection (median DSS 5 vs 0.35 years, P < .0001). Factors associated with DSS on multivariate analysis included advanced T-stage (HR 16.5 (CI 2.2-123.4), P = .0006) and lymph node metastasis (HR 1.1 (CI 1.0-1.2), P < .0001). Stage-specific survival following R0 resection was similar to patients with conventional gastric cancer. CONCLUSIONS: Patients have a lifetime risk for the development of GRC following resection for PUD. As with conventional gastric cancer, determinants of survival of patients with GRC include advanced T stage and nodal metastasis. Patients with GRC amenable to curative resection exhibit the best DSS and have stage-specific outcomes similar to patients with conventional gastric cancer.

Pyogenic abscess after hepatic artery embolization: a rare but potentially lethal complication.

PURPOSE: Hepatic artery embolization (HAE) is used commonly to treat liver tumors or hemorrhage. Infectious complications are rare but carry high rates of morbidity and mortality. Identification of clinical factors associated with postembolization abscess may improve management and outcome. MATERIALS AND METHODS: Clinical and pathologic variables of patients treated with HAE were collected and analyzed to determine the etiology, incidence, and outcome of pyogenic hepatic abscess. RESULTS: From January 1998 to January 2010, 971 patients underwent 2,045 HAE procedures. Fourteen patients developed a pyogenic hepatic abscess after embolization, for an overall rate of 1.4%. Thirty-four patients (4%) had a history of bilioenteric anastomosis (BEA) and 21 patients (2%) lacked a competent sphincter of Oddi because of the presence of a biliary stent (n = 19) or a previous sphincterotomy (n = 2). Eleven of the 34 patients with a BEA (33%) and two of 21 patients with an incompetent sphincter (10%) developed abscesses, in contrast to only one abscess (0.05%) among the 916 patients with apparently normal sphincters (0.1%; odds ratio, 437.6; 95% CI, 54.2-3,533; P < .0001). Gram-negative and Gram-positive aerobes were the most common bacteria isolated after drainage. Percutaneous drainage was the initial management strategy in all patients; two patients (14%) required subsequent surgical drainage and hepatectomy, and three (21%) died. CONCLUSIONS: Pyogenic hepatic abscess is rare after HAE. A history of BEA or an incompetent sphincter of Oddi caused by a biliary stent or previous sphincterotomy substantially increases the likelihood of this highly morbid and potentially fatal complication.

Positive peritoneal cytology in patients with gastric cancer: natural history and outcome of 291 patients.

BACKGROUND: Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort. METHODS: Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS). RESULTS: From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+ , DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt+ disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt+ patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003). CONCLUSIONS: Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt+ disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.

Neoadjuvant therapy of locally advanced gastric cancer.

Treatment of gastric cancer has evolved with the advent of randomized trials demonstrating chemotherapeutic agents with efficacy in advanced disease. Level I evidence supports delivering chemotherapy in the neoadjuvant setting; the data shows improvement in progression-free and overall survival. A clinical response to therapy is associated with improved R0 resection rates, pathologic response, and outcome in patients with locally advanced disease. Early assessment of metabolic response to therapy can potentially be utilized to tailor treatment.