Jennifer F. Tseng

Pancreaticoduodenectomy With Vascular Resection: Margin Status and Survival Duration

Major vascular resection performed at the time of pancreaticoduodenectomy (PD) for adenocarcinoma remains controversial. We analyzed all patients who underwent vascular resection (VR) at the time of PD for any histology at a single institution between 1990 and 2002. Preoperative imaging criteria for PD included the absence of tumor extension to the celiac axis or superior mesenteric artery (SMA). Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. As a separate analysis, all patients who underwent PD with VR for pancreatic adenocarcinoma were compared to all patients who underwent standard PD for pancreatic adenocarcinoma. A total of 141 patients underwent VR with PD. Superior mesenteric-portal vein resections included tangential resection with vein patch (n = 36), segmental resection with primary anastomosis (n = 35), and segmental resection with autologous interposition graft (n = 55). Hepatic arterial resections were performed in 10 patients, and resections of the anterior surface of the inferior vena cava were performed in 5 patients. PD was performed for pancreatic adenocarcinoma in 291 patients; standard PD was performed in 181 and VR in 110. Median survival was 23.4 months in the group that required VR and 26.5 months in the group that underwent standard PD (P = 0.177). A Cox proportional hazards model was constructed to analyze the effects of potential prognostic factors (VR, tumor size, T stage, N status, margin status) on survival. The need for VR had no impact on survival duration. In conclusion, properly selected patients with adenocarcinoma of the pancreatic head who require VR have a median survival of approximately 2 years, which does not differ from those who undergo standard PD and is superior to historical patients believed to have locally advanced disease treated nonoperatively.

Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma

Objective:To better understand the impact of a microscopically positive margin (R1) on patterns of disease recurrence and survival after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. Summary Background Data:A positive resection margin after PD is considered to be a poor prognostic factor, and some have proposed that an R1 margin may be a biologic predictor of more aggressive disease. The natural history of patients treated with contemporary multimodality therapy who underwent a positive margin PD has not been described. Methods:We analyzed our experience from 1990 to 2004, which included the prospective use of a standardized system for pathologic analysis of all PD specimens. All patients who underwent PD met objective computed tomographic criteria for resection. Standard pathologic evaluation of the PD specimen included permanent section analysis of the final bile duct, pancreatic, and superior mesenteric artery (SMA) margins. First recurrences (all sites) were defined as local, regional, or distant. Survival and follow-up were calculated from the date of initial histologic diagnosis to the dates of first recurrence or death and last contact, respectively. Results:PD was performed on 360 consecutive patients with pancreatic adenocarcinoma. Minimum follow-up was 12 months (median, 51.9 months). The resection margins were negative (R0) in 300 patients (83.3%) and positive (R1) in 60 (16.7%); no patients had macroscopically positive (R2) margins. By multivariate analysis (MVA), high mean operative blood loss and large tumor size were independent predictors of an R1 resection. Patients who underwent an R1 resection had a median overall survival of 21.5 months compared with 27.8 months in patients who underwent an R0 resection. After controlling for other variables on MVA, resection status did not independently affect survival. By MVA, only lymph node metastases, major perioperative complications, and blood loss adversely affected survival. Conclusions:There was no statistically significant difference in patient survival or recurrence based on R status. However, this series is unique in the incorporation of a standardized surgical technique for the SMA dissection, the prospective use of a reproducible system for pathologic evaluation of resection margins, the absence of R2 resections, and the frequent use of multimodality therapy.

Perioperative Mortality for Pancreatectomy: A National Perspective

Objective:To analyze in-hospital mortality after pancreatectomy using a large national database. Summary and Background Data:Pancreatic resections, including pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy, remain the only potentially curative interventions for pancreatic cancer. The goal of this study was to define factors affecting outcomes after pancreatectomy for neoplasm. Methods:A retrospective analysis was performed using all patients undergoing pancreatic resections for neoplastic disease identified from the Nationwide Inpatient Sample from 1998 to 2003. Crude in-hospital mortality was analyzed by χ2. A multivariable model was constructed to adjust for age, sex, hospital teaching status, hospital surgical volume, year of resection, payer status, and selected comorbid conditions. Results:In all, 279,445 patient discharges were identified with a primary diagnosis of pancreatic neoplasm. A total of 39,463 (14%) patients underwent resection during that hospitalization. In-hospital mortality was 5.9% with a significant decrease from 7.8% to 4.6% from 1998 to 2003 by trend analysis (P < 0.0001). Resections done at low (<5 procedures/year)- and medium (5–18/year)-volume centers had higher mortality compared with those at high (>18/year)-volume centers (low-volume odds ratio = 3.3; 95% confidence interval, 2.3–4.; medium-volume, odds ratio = 2.1; 95% confidence interval, 1.5–3.0). The proportion of procedures performed at high volume centers increased from 30% to 39% over the 6-year time period (P < 0.0001) by trend test. Conclusions:This large observational study demonstrates an improvement in operative mortality for patients undergoing pancreatectomy for neoplastic disease from 1998 to 2003. In addition, a greater proportion of pancreatectomies were performed at high-volume centers in 2003. The regionalization of pancreatic surgery may have partially contributed to the observed decrease in mortality rates.

Serous Cystadenoma of the Pancreas: Tumor Growth Rates and Recommendations for Treatment

Objective:To define the natural history and optimal management of serous cystadenoma of the pancreas. Summary Background Data:Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. Methods:A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976–2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. Results:Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 ± 3.1 cm, which did not vary by location. Tumors <4 cm were less likely to be symptomatic than were tumors ≥4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors <4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors ≥4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. Conclusions:Large (>4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms.

Pancreatic neuroendocrine tumors: the impact of surgical resection on survival

Although surgical resection is generally recommended for patients with localized pancreatic neuroendocrine tumors (PNETs), the impact of resection on overall survival is unknown. The authors investigated the survival advantage of pancreatic resection using a national database.

Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naïve Advanced Non–Small-Cell Lung Cancer

PURPOSE This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. PATIENTS AND METHODS Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. RESULTS The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. CONCLUSION The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.

Surgeon volume impacts hospital mortality for pancreatic resection.

Objective:Improved outcomes after pancreatic resection (PR) by high volume (HV) surgeons have been reported in single center studies, which may be confounded with potential selection and referral bias. We attempted to determine if improved outcomes by HV surgeons are reproducible when patient demographic factors are controlled at the population level. Methods:Using the Nationwide Inpatient Sample, discharge records with surgeon identifiers for all nontrauma PR (n = 3581) were examined from 1998 to 2005. Surgeons were divided into 2 groups: (HV; ≥5 operations/year) or low volume (LV; <5 operations/year). We created a logistic regression model to examine the relationship between surgeon type and operative mortality while accounting for patient and hospital factors. To further eliminate differences in cohorts and determine the true effect of surgeon volume on mortality, case-control groups based on patient demographics were created using propensity scores. Results:One hundred thirty-four HV and 1450 LV surgeons performed 3581 PR in 742 hospitals across 12 states that reported surgeon identifier information over the 8-year period. Patients who underwent PR by HV surgeons were more likely to be male, white raced, and a resident of a high-income zip code (P < 0.05). Significant independent factors for in-hospital mortality after PR included increasing age, male gender, Medicaid insurance, and surgery by HV surgeon. HV surgeons had a lower adjusted mortality compared with LV surgeons (2.4% vs. 6.4%; P < 0.0001). Conclusions:After controlling for patient demographics and factors, pancreatic resection by a HV surgeon in this case-controlled cohort was independently associated with a 51% reduction in in-hospital mortality.

Long-term survival after surgical management of neuroendocrine hepatic metastases

BACKGROUND Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases. METHODS Patients (n= 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival. RESULTS The median age was 56.8 years (range 11.5-80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3-56.8, P= 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P approximately 0.8). DISCUSSION Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival.

National Complication Rates after Pancreatectomy: Beyond Mere Mortality

IntroductionNational studies on in-hospital pancreatic outcomes have focused on mortality. Non-fatal morbidity affects a greater proportion of patients.MethodsThe Nationwide Inpatient Sample 1998–2006 was queried for discharges after pancreatectomy. Rates of major complications (myocardial infarction, aspiration pneumonia, pulmonary compromise, perforation, infection, deep vein thrombosis/pulmonary embolism, hemorrhage, or reopening of laparotomy) were assessed. Predictors of complication(s) were evaluated using logistic regression. Their independent effect on in-hospital mortality, length of stay, and discharge disposition was assessed.ResultsOf 102,417 patient discharges, 22.7% experienced a complication. Complication rates did not decline significantly over time, while mortality rates did. Independent predictors of complications included age ≥75 [referent, 19–39; adjusted odds ratio (OR) 1.34, 95% confidence interval (CI) 1.2–1.5, p < 0.0001], total pancreatectomy (vs proximal, OR 1.29, 95%CI 1.1–1.5, p = 0.0025), and low hospital resection volume (vs high, OR 1.61, 95%CI 1.4–1.8, p < 0.0001). Complications were a significant independent predictor of death (OR 7.76, 95%CI 6.7–8.8, p < 0.0001), prolonged hospital stay (OR 6.94, 95%CI 6.2–7.7, p < 0.0001), and discharge to another facility (OR 0.28, 95%CI 0.26–0.3, p < 0.0001).ConclusionsDespite improvements in mortality, complication rates remain substantial and largely unchanged. They predict in-hospital mortality, prolonged hospital stay, and delayed return to home. The impact on healthcare costs and quality of life deserves further study.

The effect of ethnicity on immediate reconstruction rates after mastectomy for breast cancer

Multiple factors may influence whether patients undergo immediate breast reconstruction along with mastectomy for breast cancer. The authors investigated whether ethnicity was an independent predictor of immediate breast reconstruction.