Impact of selection bias on the utilization of adjuvant therapy for pancreas adenocarcinoma.

BACKGROUND: Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications. METHODS: A prospectively maintained database was reviewed to identify patients who underwent potentially curative resection of histologically confirmed pancreas adenocarcinoma at our institution from January 1996 to May 2007. Clinicopathological data and postoperative treatment history were collected to identify variables associated with receipt of adjuvant therapy. RESULTS: Of 119 patients, 33% did not receive adjuvant therapy. The frequency with which patients underwent adjuvant therapy did not change over time. On multivariate analysis, patient age 70 years or greater, major postoperative complications, distal pancreatectomy, absence of nodal metastases, and absence of perineural invasion were associated with decreased utilization of adjuvant therapy. DISCUSSION: One-third of patients in this contemporary dataset of patients did not go on to receive adjuvant therapy. The likelihood of receiving adjuvant treatment is negatively impacted by the course of postoperative recovery. Moreover, the fact that adjuvant therapy was undertaken less often for older patients and patients with favorable pathological features highlights the selection bias impacting the decision to pursue postoperative therapy for this disease. This selective utilization of postoperative therapy for patients with adverse oncological characteristics is likely to bias any retrospective analysis attempting to measure the efficacy of adjuvant treatment for pancreas adenocarcinoma.

Staging laparoscopy enhances the detection of occult metastases in patients with pancreatic adenocarcinoma.

BACKGROUND: The use of staging laparoscopy has been highly institutional dependent. We sought to assess the incidence of occult intra-abdominal metastases identified at the time of staging laparoscopy for patients with either potentially resectable or locally advanced pancreatic adenocarcinoma (LAPC). We also compared the rate of occult metastases in patients who underwent staging laparoscopy versus laparotomy. METHODS: Patients were confirmed to have potentially resectable or LAPC at a multidisciplinary hepatopancreaticobiliary conference. Patients with potentially resectable lesions were initially explored via staging laparoscopy or laparotomy, based on surgeon preference. RESULTS: Over a 4-year period, 25 patients with potentially resectable tumors and 33 patients with LAPC were staged with laparoscopy, with an equivalent prevalence of occult metastases found at laparoscopy (28% potentially resectable vs. 33% LAPC, P = 0.8). Fifty-two patients with potentially resectable lesions were explored initially via laparotomy. Occult peritoneal metastases were more likely to be detected in patients with potentially resectable tumors that were explored via laparoscopy than via laparotomy (32% vs. 10%, P = 0.018). CONCLUSIONS: Staging laparoscopy is more likely than open exploration to detect occult metastases. Current preoperative imaging inadequately identifies unresectable pancreatic adenocarcinoma; therefore, all patients with potentially resectable disease should undergo staging laparoscopy.

Hilar cholangiocarcinoma: current management.

OBJECTIVE: To review the literature with regard to outcome of surgical management for hilar cholangiocarcinoma (Klatskin tumor). BACKGROUND: Hilar cholangiocarcinoma is a rare tumor with a poor prognosis. Surgical resection provides the only possibility for cure. Advances in hepatobiliary imaging and surgical strategies to treat this disease have resulted in improved postoperative outcomes. METHODS: We performed a review of the English literature on hilar cholangiocarcinoma from 1990 to 2007. This review included preoperative evaluation, surgical techniques, issues and controversies in management, prognostic variables, and considerations for future directions. RESULTS: Complete resection remains the most effective and only potentially curative therapy for hilar cholangiocarcinoma. Negative resection margins are associated with improved outcomes, and major hepatic resections have enhanced the likelihood of R0 resection. Portal vein embolization may be indicated in selected patients before extensive hepatic resection. Staging laparoscopy should be considered to detect occult metastatic disease. Orthotopic liver transplantation might be applicable for a highly selected subgroup. CONCLUSIONS: Surgical resection including major hepatic resection remains the mainstay of treatment of hilar cholangiocarcinoma. Additional evidence is needed to fully define the role of orthotopic liver transplantation. Improvements in adjuvant therapy are essential for improving long-term outcome.

Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate?

OBJECTIVE: The aim of this study was to compare the outcomes of enucleation versus resection in patients with small pancreatic, ampullary, and duodenal neuroendocrine tumors (NETs). METHODS: Multi-institutional retrospective review identified all patients with pancreatic and peri-pancreatic NETs who underwent surgery from January 1990 to October 2008. Patients with tumors < or =3 cm and without nodal or metastatic disease were included. RESULTS: Of the 271 patients identified, 122 (45%) met the inclusion criteria and had either an enucleation (n = 37) and/or a resection (n = 87). Enucleated tumors were more likely to be in the pancreatic head (P = 0.003) or functioning (P < 0.0001) and, when applicable, less likely to result in splenectomy (P = 0.0003). The rate of pancreatic fistula formation was higher after enucleation (P < 0.01), but the fistula severity tended to be worse following resection (P = 0.07). The enucleation and resection patients had similar operative times, blood loss, overall morbidity, mortality, hospital stay, and 5-year survival. However, for pancreatic head tumors, enucleation resulted in decreased blood loss, operative time, and length of stay compared to pancreaticoduodenectomy (P < 0.05). CONCLUSION: These data suggest that most outcomes of enucleation and resection for small pancreatic and peri-pancreatic NETs are comparable. However, enucleation has better outcomes than pancreaticoduodenectomy for head lesions and the advantage of preserving splenic function for tail lesions.

Resection of hilar cholangiocarcinoma: concomitant liver resection decreases hepatic recurrence.

BACKGROUND: Hilar cholangiocarcinoma is an uncommon tumor with a poor prognosis. We sought to evaluate recurrence patterns and prognostic factors for disease-specific and disease-free survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 21 years. METHODS: From 1985 to 2006, all patients with hilar cholangiocarcinoma referred to a tertiary surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients treated in a recent era (1995-2006) compared with an earlier era (1985-1994). RESULTS: Of 91 patients evaluated, 22 patients (24%) had unresectable disease at presentation. Of the 69 patients submitted to laparotomy, resection was possible in 55% and the curative (R0) resection rate was 63%. In patients submitted to exploration, the operative (60 day) morbidity and mortality rates were 26% and 3%. Median disease-specific (DSS) and disease-free survival (DFS) were 29 and 20 months, respectively (median FU, 29 months.). In patients undergoing R0 resection, the median survival was prolonged (65 months). In the more recent era, resectability rates improved (69% vs. 17%; P = 0.0002), and this was associated with an improvement in median survival (30 vs. 4 months; P < 0.001). Factors predictive of improved disease-specific and disease-free survival included negative histologic margins, concomitant hepatic lobectomy, lack of nodal disease, well-differentiated histology, and an earlier tumor stage (P < 0.05). Concomitant liver resection was associated with a higher R0 resection rate (P = 0.006) and improved DSS and DFS (P = 0.005). In addition, concomitant liver resection was associated with a decreased incidence of initial recurrence in liver (P = 0.031). CONCLUSIONS: In patients with hilar cholangiocarcinoma, concomitant hepatic resection is associated with improved DFS, DSS, and decreased hepatic recurrence. Therefore, hepatectomy combined with bile duct resection should be considered standard treatment.

Alcohol consumption by cirrhotic subjects: patterns of use and effects on liver function.

OBJECTIVE: We investigated patterns of use of alcohol and its clinical effects among cirrhotic subjects who participated in a randomized clinical trial comparing the efficacy of transjugular intravenous portosystemic shunt and distal splenorenal shunt. METHODS: There were 132 cirrhotic subjects, 78 with alcoholic liver disease (ALD), who were followed for a median of 49 months (range 2-93 months). Alcohol use was assessed by patient questionnaire, with corroboration by family members. RESULTS: Twenty-eight subjects (21%) were drinking at study entry and 60 subjects (45%) drank during follow-up. Heavy drinking (>4 drinks/day) was recorded in 25 ALD subjects, but in no non-ALD subjects (P < 0.0001). Drinking by ALD subjects was associated with a 153% increase in gamma-glutamyl transpeptidase (GGT) (P < 0.0001). The frequencies of death (46%vs 30%), ascites (33%vs 20%), encephalopathy (56%vs 42%), and variceal bleeding (11%vs 3%) were greater in the ALD group. In a Cox proportional hazards model only "ever heavy drinking" was associated with death (P= 0.0099), while recent heavy drinking increased the hazard of variceal hemorrhage dramatically (odds ratio 10.85). CONCLUSIONS: Whereas most cirrhotic subjects, alcoholic or not, did not drink during 5 yr of observation, heavy alcohol use occurred exclusively in ALD patients. Alcohol use by ALD subjects was associated with elevations in GGT and was linked to death and with rebleeding from shunt dysfunction.

Are surgical progeny more likely to pursue a surgical career?

BACKGROUND: For nearly two decades, interest in general surgery has been declining among U.S. medical school graduates. Many factors appear to be important in a medical student's choice of a surgical residency and career. We hypothesized that previous exposure to family members who are surgeons would significantly influence a student's decision to pursue a career in surgery. METHODS: Since 2001, nearly 600 third-year medical students completing the general surgery clerkship were issued a pre- and post-clerkship survey. Responses were collected, retrospectively analyzed, and correlated to the 2001-2007 National Residency Matching Program match results. RESULTS: The response rate of students completing both surveys was 87% (n = 510). Based on a numeric scale, surgical progeny (SP) indicated a significantly higher likelihood than nonsurgical progeny (NSP) of pursing a surgical career/residency in the pre-clerkship period (SP mean, 5.1 +/- 0.42; NSP mean, 3.7 +/- 0.11; P = 0.0005). Post-clerkship, SPs noted no more enjoyment from the surgical clerkship than NSPs (SP mean, 7.2 +/- 0.25; NSP mean, 6.9 +/- 0.96; P = 0.91); furthermore, there was no difference in the percentage of students pursuing a surgical residency (categorical or surgical subspecialty) in the National Residency Matching Program match (SP, 12.5%; NSP, 12.7%; P = 1.00). CONCLUSION: These data suggest that previous exposure to a surgeon within the family positively influences a medical student's pre-clerkship interest in pursuing a surgical career. However, this interest is not sustained; SPs and NSPs match into surgical residencies at equivalent rates. Clearly, further studies are needed to identify the factors responsible for this phenomenon.

Cost of preventing variceal rebleeding with transjugular intrahepatic portal systemic shunt and distal splenorenal shunt.

BACKGROUND/AIMS: We examined the cost and cost effectiveness of distal splenorenal shunt (DSRS) and transjugular intrahepatic portosystemic shunt (TIPS) in the prevention of variceal rebleeding. METHODS: Patients participated in a randomized controlled trial comparing DSRS to TIPS. Quality of life (QOL) was measured using SF-36 preceding randomization and yearly thereafter. Cost utility analysis was performed using TreeAge DATA. Costs for both in- and out-patient events and interventions were obtained for each patient. Costs using coated stents were estimated using different rates of stenosis. Incremental cost effectiveness ratios (ICERs) were determined at 1, 3 and 5 years. RESULTS: The average yearly costs of managing patients after TIPS and DSRS over 5 years were similar, $16,363 and $13,492, respectively. Cost of TIPS for surviving patients exceeded the cost of DSRS at years 3 and 5 but not significantly. ICERs per life saved favored TIPS at year 5 ($61,000). If coated rather than bare stents were used the cost effectiveness of TIPS increased slightly. CONCLUSIONS: TIPS is as effective as DSRS in preventing variceal rebleeding and may be more cost effective. TIPS, in all aspects, is equal to DSRS in the prevention of variceal rebleeding in patients who are medical failures.

Motivation to pursue surgical subspecialty training: is there a gender difference?

BACKGROUND: Few studies have examined whether women and men identify the same factors as important in choosing their specialty. We sought to evaluate whether the factors influencing residents' choice of surgical specialty differed by gender. STUDY DESIGN: A 32-item Web survey, designed to elucidate which factors motivated residents to seek fellowship training, was sent to 99 graduates of a university general surgery program, all of whom matriculated between 1985 and 2006. RESULTS: A total of 74 (75%) respondents replied (16 women, 58 men). There was a higher proportion of men who pursued fellowship training than women (69% versus 38%, p=0.04), but there was no significant difference in those who were currently in academic practice (men, 46% versus women, 27%, p=0.2). Both genders were equally likely to respond that interest in and intellectual appeal of their field, clinical opportunities in that field, and having an influential mentor during residency were important in choosing their future specialty. But significantly more women listed lifestyle as an important factor in choosing their future careers (69% versus 43%, p=0.03). When respondents' data from the most recent decade were analyzed, there was no difference between genders in completion of fellowship training or in those in academic practice. But lifestyle continued to be more important to women. CONCLUSIONS: Both genders were influenced by many similar factors when deciding to pursue subspecialty training, but women were more likely than men to be influenced by their perception of the lifestyle associated with their career choice. These findings suggest that general surgical residency programs might improve efforts to recruit women by addressing the perception of the lifestyle associated with choosing a surgical career.

Computed tomography in the diagnosis of acute appendicitis: definitive or detrimental?

OBJECTIVES: Utilization of computed tomography (CT) scans in patients with presumed appendicitis was evaluated at a single institution to determine the sensitivity of this diagnostic test and its effect on clinical outcome. METHODS: Adult patients (age > 17 years) with appendicitis were identified from hospital records. Findings at surgery, including the incidence of perforation, were correlated with imaging results. RESULTS: During a 3-year period, 411 patients underwent appendectomy for presumed acute appendicitis at our institution. Of these patients, 256 (62%) underwent preoperative CT, and the remaining 155 (38%) patients did not have imaging before the surgery. The time interval between arrival in the emergency room to time in the operating room was longer for patients who had preoperative imaging (8.2 +/- 0.3 h) compared to those who did not (5.1 +/- 0.2 h, p < 0.001). Moreover, this possible delay in intervention was associated with a higher rate of appendiceal perforation in the CT group (17 versus 8%, p = 0.017). CONCLUSIONS: Preoperative CT scanning in patients with presumed appendicitis should be used selectively as widespread utilization may adversely affect outcomes. The potential negative impact of CT imaging includes a delay in operative intervention and a potentially higher perforation rate.

Effective surgical residents strongly influence medical students to pursue surgical careers.

BACKGROUND: There is a paucity of data about the influence of surgical residents on the career choices of medical students. We hypothesized that medical students exposed to effective surgical residents would be more likely to pursue careers in surgery. STUDY DESIGN: From 1998 to 2003, 108 surgical residents were evaluated by medical students rotating on the third-year clerkship. Residents were scored on a 4-point scale (1 = outstanding to 4 = poor). The career choices of all medical students were also tabulated. RESULTS: We examined 2,632 evaluations on 108 residents. Medical students who eventually pursued surgical residency training were exposed to surgical residents who were more effective clinical teachers, role models, and overall residents. In addition, medical students exposed to the highest-rated residents were more likely to pursue surgical residency training compared with students exposed to the least effective residents (12% versus 4.9%, p = 0.022). CONCLUSIONS: These data suggest that surgical residents who are effective educators and mentors influence medical students to pursue surgical careers. Efforts to provide more leadership and teaching workshops to surgical residents may not only create better future surgeon educators, but may also increase the number of students pursuing surgical training.

Metastatic neuroendocrine hepatic tumors: resection improves survival.

BACKGROUND: The optimal treatment for hepatic metastases from neuroendocrine tumors remains controversial because of the often indolent nature of these tumors. We sought to determine the effect of 3 major treatment modalities including medical therapy, hepatic artery embolization, and surgical resection, ablation, or both in patients with liver-only neuroendocrine metastases, with the hypothesis that surgical treatment is associated with improvement in survival. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Patients with metastatic liver-only neuroendocrine tumors were identified from hospital records. INTERVENTIONS: Patients were subdivided into those receiving medical therapy, hepatic artery embolization, or surgical management. MAIN OUTCOME MEASURES: Effect of treatment on survival and palliation of symptoms was analyzed. RESULTS: From January 1996 through May 2004, 48 patients with liver-only neuroendocrine metastases were identified (median follow-up, 20 months), including 36 carcinoid and 12 islet cell tumors. Seventeen patients were treated conservatively, which consisted of octreotide (n = 7), observation (n = 6), or systemic chemotherapy (n = 4). Hepatic artery embolization was performed in 18 patients. Thirteen patients underwent surgical therapy, including anatomical liver resection (n = 6), ablation (n = 4), or combined resection and ablation (n = 3). No difference was noted in the percentage of liver involved with tumor between the 3 groups. An association of improved survival was noted in patients treated surgically, with a 3-year survival of 83% for patients treated by surgical resection, compared with 31% in patients treated with medical therapy or embolization (P = .01). No difference in palliation of symptoms was noted among the 3 treatment groups (P = .2). CONCLUSION: In patients with liver-only neuroendocrine metastases, surgical therapy using resection, ablation, or both is associated with improved survival.

Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial.

BACKGROUND & AIMS: Variceal bleeding refractory to medical treatment with beta-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. METHODS: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 +/- 26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. RESULTS: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81% and 62%; TIPS, 88% and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. CONCLUSIONS: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.

Current management of portal hypertension.

Portal hypertension can lead to life-threatening hemorrhage, ascites, and encephalopathy. This paper reviews the pathophysiology and multidisciplinary management of portal hypertension and its complications, including the indications for and techniques of the various surgical shunts. Variceal bleeding is the most dreaded complication of portal hypertension. It may occur once the portal-systemic gradient increases above 12 mm Hg, occurs in 30% of patients with cirrhosis, and carries a 30-day mortality of 20%. Treatment of acute variceal bleeding includes resuscitation followed by upper endoscopy for sclerosis or band ligation of varices, which can control bleeding in up to 85% of patients. Medical therapies such as vasopressin and somatostatin can also be useful adjuncts. Shunt therapy, preferably the placement of a TIPS, is indicated for refractory acute variceal bleeding. Recurrent variceal bleeding is common and is associated with a high mortality. Therapies to prevent recurrent variceal bleeding include chronic endoscopic therapy, nonselective beta-blockade, operative or nonoperative (TIPS) shunts, devascularization operations, and liver transplantation. Recommendations and a treatment algorithm are provided, taking into account both the etiology and the manifestations of portal hypertension.