Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer.

BACKGROUND AND OBJECTIVES: Preoperative chemoradiotherapy for locally advanced rectal cancer is now considered "standard of care." However, the optimal time interval for resection after neoadjuvant therapy is unknown. METHODS: Between 11/90 and 11/04, 107 patients with rectal adenocarcinoma underwent preoperative chemo/RT at the University of Pennsylvania. Fifty-six percent had LAR and 40% had APR. Chemotherapy consisted of 5-FU/oxaliplatin in 28% and 5-FU in 72% of patients. All patients received preoperative RT. RESULTS: A longer time interval between chemo/RT and surgery was associated with tumor downstaging (OR 1.24, P = 0.02). A longer time interval was not associated with: nodal downstaging (OR 1.00, P = 0.98); pathologic complete response (PCR) (OR 0.97, P = 0.80); likelihood of performing an LAR (OR 0.90, P = 0.47); improved disease free survival (DFS), local control, or distant control (HR 1.05, P = 0.49; HR 1.14, P = 0.22; HR 1.06, P = 0.52, respectively). The PCR rate was 34.5% in the 5-FU/oxaliplatin/radiation group, and 13.7% in the 5-FU/radiation group. If patients with microscopic CR were excluded, then the PCR rate for 5FU/OX was 21.4% and for 5-FU was 12.2%. CONCLUSIONS: Time interval between surgery and chemo/RT appeared to have little effect on PCR or LAR rates. Patients receiving 5 FU/oxaliplatin/RT had a high PCR rate. A prospective randomized trial to test superiority of 5 FU/oxaliplatin is warranted.

Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma.

BACKGROUND: Nonoperative therapy with intent to cure may be considered for patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. However, a more advanced stage of disease must be precluded before such treatment. The potential of EUS for this purpose was evaluated. METHODS: EUS was performed in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma based on endoscopy, endoscopic biopsies, and CT before esophagectomy. EUS findings were compared with surgical/pathologic evaluation. RESULTS: EUS suggested submucosal invasion in 6 patients and lymph node involvement in 5 patients. By surgical/pathologic evaluation, 5 of 22 patients (23%) had unsuspected submucosal invasion and 1 had lymph node involvement. EUS detected all 5 instances of submucosal invasion and the single instance of lymph node involvement. EUS was falsely positive for submucosal invasion in 1 patient and for lymph node involvement in 4 patients. Sensitivity, specificity, and negative predictive values of preoperative EUS for submucosal invasion were 100%, 94%, and 100%, and for lymph node involvement were 100%, 81%, and 100%, respectively. A nodule or stricture noted by endoscopy was associated with an increased likelihood of submucosal invasion. CONCLUSIONS: In patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma, EUS detected otherwise unsuspected submucosal invasion and lymph node involvement. Patients should be evaluated with EUS when nonoperative therapy is contemplated.

Long term survival after pancreatic resection for pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.

Fragile histidine triad expression delays tumor development and induces apoptosis in human pancreatic cancer.

The fragile histidine triad (FHIT) gene is a tumor suppressor gene that is altered by deletion in a large fraction of human tumors, including pancreatic cancer. To evaluate the potential of FHIT gene therapy, we developed recombinant adenoviral and adenoassociated viral (AAV) FHIT vectors and tested these vectors in vitro and in vivo for activity against human pancreatic cancer cells. Our data show that viral FHIT gene delivery results in apoptosis by activation of the caspase pathway. Furthermore, Fhit overexpression enhances the susceptibility of pancreatic cancer cells to exogenous inducers of apoptosis. In vivo results show that FHIT gene transfer delays tumor growth and prolongs survival in a murine model mimicking human disease.

The impact of a multidisciplinary breast cancer center on recommendations for patient management: the University of Pennsylvania experience.

BACKGROUND: Advances in the diagnosis and treatment of breast carcinoma have led to a multidisciplinary approach to management for patients with breast carcinoma. To assess the effect of this approach, the authors performed an evaluation for a cohort of patients examined in a multidisciplinary breast cancer center. METHODS: An analysis was performed for the records of 75 consecutive women with 77 breast lesions examined in consultation in a multidisciplinary breast cancer center between January and June 1998. Each patient's case was evaluated by a panel consisting of a medical oncologist, surgical oncologist, radiation oncologist, pathologist, diagnostic radiologist, and, when indicated, plastic surgeon. A comprehensive history and physical examination was performed, and the relevant mammograms, pathology slides, and medical records were reviewed. Treatment recommendations made before this evaluation were compared with the consensus recommendations made by the panel. RESULTS: For the 75 patients, the multidisciplinary panel disagreed with the treatment recommendations from the outside physicians in 32 cases (43%), and agreed in 41 cases (55%). Two patients (3%) had no treatment recommendation before consultation. For the 32 patients with a disagreement, the treatment recommendations were breast-conservation treatment instead of mastectomy (n = 13; 41%) or reexcision (n = 2; 6%); further workup instead of immediate definitive treatment (n = 10; 31%); treatment based on major change in diagnosis on pathology review (n = 3; 9%); addition of postmastectomy radiation treatment (n = 3; 9%); or addition of hormonal therapy (n = 1; 3%). CONCLUSIONS: The multidisciplinary breast cancer evaluation program provided an integrated program in which individual patients were evaluated by a team of physicians and led to a change in treatment recommendation for 43% (32 of 75) of the patients examined. This multidisciplinary program provided important second opinions for many patients with breast carcinoma.

Crohn's disease of the colon.

The surgical treatment of Crohn's disease of the colon is distinct from that used in treating ulcerative colitis. Crohn's disease often involves the small bowel and is not "cured" by colorectal resection. The popular ileo-anal pouch procedures used in the management of ulcerative colitis generally are not used for the treatment of Crohn's colitis, because of higher complication rates. Commonly performed operations include ileostomy, segmental colon resection, subtotal colectomy, and proctocolectomy. The general surgeon, therefore, is provided with many options when faced with complications of Crohn's colitis. This article examines the attributes of and results reported for each of these options.

Endosonography is superior to angiography in the preoperative assessment of vascular involvement among patients with pancreatic carcinoma.

Surgical exploration in patients with pancreatic carcinoma without adequate preoperative attempts to determine resectability results in resection in only a minority of patients. Besides distant metastases, involvement of the major vessels is the most important parameter for determining resectability in patients with pancreatic adenocarcinoma. Angiography has been an integral part of pancreatic cancer staging. Lately, endoscopic ultrasound (EUS) has emerged as a more accurate tool in the diagnosis and staging of pancreatic cancer. We hypothesize that EUS is more accurate than selective venous angiography (SVA) for assessing resectability of pancreatic adenocarcinoma based on preoperative evaluation of vascular involvement. Twenty-one patients who met the inclusion criteria were prospectively evaluated with both EUS and SVA before undergoing surgical exploration for attempted curative resection. Vascular involvement was determined by EUS and SVA using previously described criteria. The sensitivity, specificity, and overall accuracy of EUS and SVA in assessing vascular involvement were compared, using surgical exploration as the gold standard. Endoscopic ultrasound had a higher sensitivity than SVA for detecting vascular involvement (86% vs. 21%, respectively; p = 0.0018). The specificity and accuracy of EUS for detecting vascular involvement was 71% and 81%, respectively. In contrast, the specificity and accuracy of SVA for detecting vascular involvement was 71% and 38%, respectively. Endoscopic ultrasound is significantly more sensitive than angiography for detecting vascu lar involvement in patients with pancreatic adenocarcinoma and, thus, may improve patient selection for attempted curative resection.

Hand-assisted laparoscopic vertical banded gastroplasty: early results.

BACKGROUND: Minimally invasive hand-port-assisted laparoscopic vertical banded gastroplasty has the potential to reduce postoperative complications after bariatric surgery. METHODS: We analyzed the postoperative course of 46 hand-port-assisted laparoscopic vertical banded gastroplasties (LVBG) completed between January 1998 and April 1999. RESULTS: The operating time for the LVBG was shorter (140.8 +/- 6.0 vs 180.2 +/- 6.3 min; p < 0.05). Individuals were able to ambulate sooner (1.36 +/- 0.09 vs 2.44 +/- 0.16 days; p < 0.05), and start oral intake earlier (2.7 +/- 0.27 vs 3.7 +/- 0.17 days; p < 0.05) than the open vertical banded gastroplasty (VBG) controls. Three staple line leaks were detected in this group. Two leaks resolved without clinical sequelae, but one patient developed intraabdominal sepsis. This complication extended the average hospital stay to 6.8 +/- 2.00 days, as compared to 7.71 +/- 0.18 days for historical controls. By discounting this patient from the analysis, we arrive at a more representative length of hospitalization of 4.82 +/- 0.34 days (p < 0.05). CONCLUSIONS: LVBG offers a good alternative to the standard open VBG. Although this procedure has a relatively short learning curve, it should be done at centers with an interest in bariatric surgery.

EUS in preoperative staging of pancreatic cancer.

BACKGROUND: Endoscopic ultrasound (EUS) is believed to be highly accurate in the local (T) and nodal (N) staging of pancreatic cancer. However, there are scant data concerning the predictive value of EUS for resectability of pancreatic adenocarcinoma. This study was performed to determine the accuracy of TNM staging by EUS in patients with pancreatic adenocarcinoma and to evaluate the role of preoperative TNM staging by EUS for determining resectability in patients with pancreatic adenocarcinoma. METHODS: This is a retrospective review of a cohort of 89 patients evaluated preoperatively with EUS for pancreatic adenocarcinoma between January 1995 and December 1997. Preoperative TNM classification by EUS was compared with surgical and histopathologic TNM staging. Resectability rates were determined and compared with the preoperative TNM staging by EUS. RESULTS: The overall accuracy of EUS for T and N staging was found to be 69% and 54%, respectively. The overall proportion of tumors that were deemed resectable by EUS and were actually found to be resectable during surgical exploration was 46%. The proportion of tumors staged as T4 N1, T4 N0, T3 N1 and T3 N0 by EUS that were found to be resectable during surgical exploration was 45%, 37%, 44% and 62%, respectively. CONCLUSIONS: In a tertiary referral patient population, EUS is not as accurate as previously reported in the T and N staging of pancreatic cancer. EUS is also not predictive of resectability in stage T3 or T4 pancreatic cancer.

Role of endoscopic ultrasound and magnetic resonance imaging in the preoperative staging of pancreatic adenocarcinoma.

OBJECTIVE: Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) have both been assessed individually as staging modalities for pancreatic cancer. The aim of our study was to assess whether tumor staging by both EUS and MRI in the same cohort of patients could predict resectability and unresectability in patients with pancreatic cancer. METHODS: A review of 63 patients evaluated preoperatively with both EUS and MRI for pancreatic adenocarcinoma between January 1995 and December 1998 was done. Patients were staged as resectable or unresectable by predefined criteria. Preoperative staging by both modalities was compared to surgical outcome and the sensitivity and predictive values of each modality for determining resectability and unresectability was determined. RESULTS: EUS did not allow for complete T- and N-staging in 10 patients; therefore, for EUS, the final analysis was done on 63 of 73 patients (86%). EUS correctly staged 22 of 36 patients with resectable tumors. The sensitivity of EUS for resectability was 61%, with a positive predictive value of 69%. All 73 patients had complete MRI examinations; therefore, the final analysis was done on all 73 patients. MRI correctly staged 30 of 41 patients with resectable tumors. The sensitivity of MRI for predicting resectability was 73% with a positive predictive value of 77%. MRI and EUS both predicted resectability in 18 patients, of whom 16 (89%) were found to be resectable on surgical exploration. MRI and EUS both predicted unresectability in 17 (27%) patients, of whom 4 (24%) were found to be resectable on surgical exploration. When both MRI and EUS agreed on resectability, the positive predictive value for resectability was 89%. When both MRI and EUS agreed on unresectability, the positive predictive value for unresectability was 76%. CONCLUSIONS: Neither MRI nor EUS alone were highly sensitive or predictive of resectability. However, when both tests agreed on resectability, nearly all patients were found to be resectable on surgical exploration.

Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas.

PURPOSE: To determine the clinical outcomes and potential impact of adjuvant chemoradiation in patients undergoing surgical resection of ampullary carcinoma. PATIENTS AND METHODS: Between 1988 and 1997, 39 patients underwent pancreaticoduodenectomy for ampullary adenocarcinomas. Clinical and pathologic factors, adjuvant therapy records, and disease status were obtained from chart review. Thirteen (33%) patients received adjuvant chemoradiation. Radiation therapy was delivered to the surgical bed and regional nodes to a median dose of 4,860 cGy with concurrent bolus or continuous infusion of 5-fluorouracil. Outcomes measures included locoregional control, disease-free survival, and overall survival. Univariate analysis was used to assess the impact of various patient- and tumor-related factors and the use of adjuvant therapy. Twenty (51%) patients with tumor invasion into the pancreas (T3) or node-positive disease were classified in a "high-risk" subgroup. RESULTS: After a median follow-up of 45 months for survivors, overall 3-year survival was 55%. Survival was significantly worse for patients with positive nodes (23% vs. 73%, p < 0.001) and high-risk status (30% vs. 80%, p = 0.002). Disease-free survival was 54% at 3 years. There were 3 postoperative deaths, and these patients (all high risk) are excluded from further analysis on adjuvant therapy. In univariate analysis, the use of adjuvant chemoradiation had no clear impact on local-regional control or overall survival. However, by controlling for risk status in multivariate analysis, the use of adjuvant therapy reached statistical significance for overall survival (p = 0. 03). Among the high-risk patients, 7 (77%) of 9 patients receiving adjuvant therapy remained disease-free during follow-up compared with only 1 (14%) of 7 patients not receiving adjuvant therapy (p = 0.012). CONCLUSION: Despite the relatively favorable prognosis of ampullary carcinomas compared with other pancreaticobiliary tumors, patients with nodal metastases or T3 disease are at high risk for disease relapse. The use of adjuvant chemoradiation may improve long-term disease control in these patients.

Tall cell papillary carcinoma of the thyroid: metastatic to the pancreas.

We present the case of a 53-year-old man with tall cell variant of papillary thyroid carcinoma that metastasized to the pancreas. The pancreas is a unique site of metastasis for differentiated thyroid cancer. The lesion in the neck and lung concentrated radioiodine, whereas the intrapancreatic lesions did not. Discordance between radioiodine studies and serum thyroglobulin in follow-up of patients with differentiated tall cell is reviewed and discussed.

EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms.

BACKGROUND: Computerized tomography (CT), magnetic resonance imaging (MRI), and transabdominal ultrasound frequently fail to detect ampullary lesions. Endoscopic ultrasound (EUS) is a sensitive modality for detecting and staging ampullary tumors. Accurate staging may be affected by biliary stenting, which is frequently performed in these patients with obstructive jaundice. The present study assessed the accuracy of ampullary tumor staging with multiple imaging modalities in patients with and those without endobiliary stents. METHODS: Fifty consecutive patients with ampullary neoplasms from two endosonography centers were preoperatively staged by EUS plus CT (37 patients), MRI (13 patients), or angiography (10 patients) over a 3(1/2) year period. Twenty-five of the 50 patients had a transpapillary endobiliary stent present at the time of endosonographic examination. Accuracy of EUS, CT, MRI, and angiography was assessed with the TNM classification system and compared with surgical-pathologic staging. The influence of an endobiliary stent present at the time of EUS on staging accuracy of EUS was also evaluated. RESULTS: EUS was more accurate than CT and MRI in the overall assessment of the T stage of ampullary neoplasms (EUS 78%, CT 24%, MRI 46%). No significant difference in N stage accuracy was noted between the three imaging modalities (EUS 68%, CT 59%, MRI 77%). EUS T stage accuracy was reduced from 84% to 72% in the presence of a transpapillary endobiliary stent. This was most prominent in the understaging of T2/T3 carcinomas. CONCLUSIONS: EUS is superior to CT and MRI in assessing T stage but not N stage of ampullary lesions. The presence of an endobiliary stent at EUS may result in underestimating the need for a Whipple resection because of tumor understaging.

Hartmann's pouch: radiographic evaluation of postoperative findings.

OBJECTIVE: The purpose of this study was to determine the usefulness of contrast-enhanced radiography of the Hartmann's pouch for evaluating postoperative abnormalities. MATERIALS AND METHODS: We performed a retrospective study of 84 patients with a Hartmann's pouch who underwent contrast-enhanced radiography of the pouch during a recent 7-year period. Sixty-four patients underwent single-contrast barium studies of the pouch, 17 underwent studies with a water-soluble contrast medium, and three underwent both types of studies. The radiographic studies were reviewed to determine the types and frequency of abnormalities involving the pouch. Medical records were also reviewed to determine clinical presentation and course. RESULTS: Abnormalities of the Hartmann's pouch were detected on contrast-enhanced radiography in 16 (19%) of the 84 patients. Of the 70 patients who underwent routine contrast-enhanced radiography of the pouch, 11 (16%) had abnormalities, including diversion colitis in three, leaks in two, adhesions in two, recurrent carcinoma in two, ulcerative colitis involving the pouch in one, and a stricture in one. In both patients with clinically silent leaks, the contrast-enhanced radiography was performed 3 months or more after creation of the pouch. Of the remaining 14 patients who underwent contrast-enhanced radiography because of suspected complications involving the pouch, five (36%) had abnormalities revealed, including leaks in two, fistulas in two, and recurrent carcinoma in one. CONCLUSION: Contrast-enhanced radiography of the Hartmann's pouch revealed abnormalities of the pouch in 19% of patients, including leaks or fistulas, diversion colitis, adhesions, strictures, and recurrent tumor. Because two patients had clinically silent leaks that were detected during the late postoperative period, it may be prudent to perform these studies with a water-soluble contrast medium to avoid the problems associated with extravasation of barium into the extra- or intraperitoneal spaces.

The consequences of a major bile duct injury during laparoscopic cholecystectomy.

Bile duct injury is perhaps the most feared complication of laparoscopic cholecystectomy. The focus of this study was on the immediate and short-term outcome of patients who have undergone repair of major bile duct injuries with respect to hospital stay, perioperative interventions, and reoperations. The records of patients who underwent surgery at three academic hospitals in Philadelphia (Hospital of the University of Pennsylvania, Thomas Jefferson University Hospital, and Graduate Hospital) from 1990 to 1995 for repair of a major biliary injury following laparoscopic cholecystectomy were reviewed. A major biliary injury was defined as any disruption (including ligation, avulsion, or resection) of the extrahepatic biliary system. Small biliary leaks not requiring surgery were excluded. Thirty-two patients sustained major bile duct injuries. The injury was recognized immediately in 10 patients. The remaining 22 patients had pain (59%), jaundice (50%), and/or fever (32%) as the symptom heralding the injury. Bismuth classification was as follows: 13% of patients were class I, 63% were class II, 7% were class III, 7% were class IV, and 10% were class V. Biliary reconstruction included a Roux-en-Y hepaticojejunostomy in 30 patients and two were primary repairs. There was one postoperative death from multiorgan system failure. The mean length of hospital stay after repair was 17 +/- 8 days. Over a mean follow-up period of 11.5 +/- 10.5 months, 11 patients (38%) required 19 emergency readmissions, most commonly for cholangitis. Five patients (17%) required postoperative balloon dilatation for biliary stricture. At follow-up 18 patients (62.0%) remain asymptomatic with normal liver function, eight (28%) are experiencing episodic cholangitis, and three (10%) are asymptomatic with persistently elevated liver function values. The consequences of a major biliary tract injury following laparoscopic cholecystectomy include a complex operative repair resulting in a lengthy postoperative stay with an increased risk of death, an excessive number of perioperative diagnostic and therapeutic studies, frequent readmissions (often as emergencies), and a lifelong risk of restricture. The "cost" to these patients remains enormous.

Primary carcinoid of the duodenum: detection and characterization by magnetic resonance imaging.

We report a rare case of a primary small bowel carcinoid in which high-resolution MRI was able to detect a 1-cm primary duodenal neoplasm. This case illustrates that breath-hold contrast-enhanced MRI is capable of evaluating disease of the small bowel.

Acute appendicitis secondary to metastatic bronchogenic adenocarcinoma.

Metastatic tumors to the appendix are not common. However, these tumors should be one of the differential diagnoses in patients with known primary malignancy, who present with signs and symptoms of acute appendicitis. We report a case of an elderly male with poorly differentiated bronchogenic adenocarcinoma which metastasized to the appendix.