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.

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.

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.

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.

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.

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.

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.

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.

Choledochal cysts in western adults: complexities compared to children.

Choledochal cysts occur most frequently in East Asian children and rarely in Western adults. Over the past two decades, pediatric treatment has been standardized, but relatively little information is available on the management of Western adults with choledochal cysts. Therefore the aims of this analysis were to compare the presentation, management, and late results of Western adults and children with choledochal cysts. Records were reviewed of patients with choledochal cysts at three academic institutions in Wisconsin. Fifty-seven patients were identified, and 51 of these patients (89%) were managed surgically. Thirty-one patients (54%) were adults, and the adults were more likely to be male (29% vs. 4%, P<0.02). Pain (81% vs. 42%, P<0.01) and cholangitis (35% vs. 15%) were more common in adults. Forty-one patients (71%) had type I cysts, but type IVa or V cysts with dilated intrahepatic ducts were more common in adults (39% vs. 15%, P=0.05). Seventeen adults had undergone biliary surgery prior to referral compared to only four children (59% vs. 15%, P<0.01). Preoperative endoscopic or percutaneous stents were employed more commonly in adults (42% vs. 15%, P<0.01). Hospital mortality was 0%, and morbidity was low in both adults and children (25% vs. 8%). An associated biliary malignancy correlated with age (P<0.05): 0 to 30 years (0%), 31 to 50 years (19%), and 51 to 70 years (50%). In addition, adults were more likely to have late problems with cholangitis (19% vs. 4%, P<0.07) and secondary biliary cirrhosis (13% vs. 4%). This analysis suggests that compared to children, Western adults with choledochal cysts are more likely to have (1) type IVA or V cysts, (2) undergone prior surgery, (3) preoperative biliary stents, (4) an associated biliary malignancy, and (5) late hepatobiliary problems. We conclude that surgery in Western adults with choledochal cysts is frequently complicated and should be performed by specialists in complex biliary surgery.

Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases.

Although positron emission tomography (PET) detects occult metastatic disease in approximately 20% of patients with isolated hepatic colorectal metastases, it is associated with false negative results in up to 16%. We hypothesized that patients with a poorer prognosis (as defined by clinical risk score [CRS]) would have a higher yield from PET. All patients with colorectal liver metastases who were imaged by means of PET between 1998 and 2002 were identified from a prospective PET database. All patients were assigned a CRS, with one point added for each of five preoperative factors (disease-free interval <1 year, tumor size >5 cm, tumor number >1, carcinoembryonic antigen >200, and node-positive primary lesion). A total of 85 PET scans were reviewed. In half the patients (53%), PET provided no additional information over conventional imaging. Occult extrahepatic disease was detected or questionable findings seen on conventional imaging were confirmed in 20% of PET scans, whereas PET readings were inaccurate in 27%. PET findings were correlated with CRS in a subset of 63 patients presenting with a first occurrence of hepatic colorectal metastases. Among patients with a CRS of 0, no patient had extrahepatic disease detected by PET and 57% had false positive readings, whereas among patients with a CRS of 1 or more, 14% were found to have additional disease that was detected only by PET, and there were no false positive readings (P<0.001, Fisher's exact test). Patients with isolated hepatic colorectal metastases and a CRS of 0 should undergo conventional imaging alone prior to surgical exploration.

Should suspected early gallbladder cancer be treated laparoscopically?

Early gallbladder cancer (EGC), defined as T1 and T2 disease, is frequently curable when completely excised without bile spillage. The objective of the present study was to determine what effect initial laparoscopic cholecystectomy has on outcome in patients with EGC. Of 89 patients referred to our institution with gallbladder cancer over an 11-year period, 26 had undergone initial laparoscopic cholecystectomy. Sixteen of the 26 patients had T1 or T2 disease and are the subjects of this report. These patients were reviewed retrospectively to assess preoperative diagnosis, intraoperative bile spillage, and outcome (recurrence and survival). In addition, the Western literature was reviewed to determine the impact of initial laparoscopic cholecystectomy on recurrence and survival of patients with EGC. Six patients had a preoperative ultrasound consistent with a mass in the gallbladder wall. Seven (44%) had documented bile spillage during the laparoscopic cholecystectomy. T stage based on the laparoscopic cholecystectomy was T1 (n = 1) and T2 (n = 15). Twelve patients underwent reexploration of whom seven underwent further radical excision (gallbladder liver bed resection and extensive lymphadenectomy). After a mean follow-up of 20.1 months (range 4 to 39 months), 69% of patients have had a recurrence or died. Three patients had a port-site recurrence. Five (71%) of seven patients with bile spillage at laparoscopic cholecystectomy have had a recurrence or died of disease. A review of the Western literature on EGC initially removed by laparoscopic cholecystectomy (including the present series) yielded 21 patients with T1 and 42 patients with T2 disease. One-year Kaplan-Meier survival (T1 = 89%, T2 = 71%) and 3-year Kaplan-Meier survival (T1 = 47%, T2 = 40%) of these patients is worse than prior reports for open cholecystectomy. An initial laparoscopic cholecystectomy with its potential for bile spillage can convert potentially curable EGC to incurable disease. Patients with preoperative findings suspicious for gallbladder cancer should undergo open exploration with intent to perform a radical cancer operation as a primary procedure if the diagnosis is confirmed intraoperatively.

Medical student operative experience correlates with a match to a categorical surgical program.

BACKGROUND: Interest in general surgical residencies has decreased significantly. Because medical student clerkship experiences may affect specialty preferences, we attempted to determine if the degree of exposure to surgical procedures influenced career choices. METHODS: Operations observed by students who completed the third-year surgical clerkship between 1998 and 1999 were reviewed. These 146 medical students, who matched to residency training programs in March 2000, were then divided into three groups based upon residency fields. Surgical case exposures were then compared between the groups. RESULTS: The total number of operations observed was similar between the groups. However, students who matched into categorical general surgical programs participated in significantly more abdominal and general surgical procedures than those matching in surgical subspecialty or nonsurgical residencies (P < 0.01). CONCLUSIONS: There appears to be a correlation between surgical case exposure during the third-year clerkships and future residency fields. Thus, the degree of exposure to surgical procedures may influence medical student career choices.

Cryoablation and liver resection for noncolorectal liver metastases.

BACKGROUND: Liver resection for noncolorectal liver metastases has merit for selected primary tumor types. The role of cryosurgical tumor ablation within this cohort of patients has not been evaluated. This is a single institutional review of treatment outcomes using cryosurgical ablation and conventional resection techniques for noncolorectal liver metastases. METHODS: The medical records of 42 patients undergoing 48 hepatic tumor ablative procedures from February 1991 through May 2001 at a single institution were retrospectively reviewed. Overall survival and local hepatic tumor recurrence-free survival were analyzed for different surgical procedures and primary tumor types. RESULTS: Overall survival rates at 1, 3, and 5 years are 82%, 55%, and 39%, respectively (median survival, 45 months). Local hepatic tumor recurrence-free survival rates for resection only (n = 25) and cryosurgery with or without resection (n = 23), at 3 years are 24% and 19%, respectively. The survival rates at 5 years are 40% and 37%, for resection only and cryosurgery with or without resection, respectively. CONCLUSION: Cryosurgical hepatic tumor ablation for metastatic noncolorectal primary tumors results in survival and local hepatic tumor recurrence rates similar to resection alone. The combination of cryosurgery and resection extends the cohort of patients with surgically treatable disease.