Esophageal cancer--the five year survivors.

BACKGROUND: Esophageal cancer in the United States carries a poor prognosis with overall 5 year survival rate of approximately 10%. Due to this dismal outcome, data analyzing factors predictive of survival for greater than 5 years are not available. METHODS: Single institution retrospective review of esophageal resection for curative intent from 1984 to 2004. We identified 50 actual 5 year survivors (long term survivors, LTS) out of 266 patients (19%) with invasive esophageal cancer and, using multivariate logistic regression, compared characteristics between the LTS, and short-term (<5 year) survivors (STS). RESULTS: There was no significant difference in clinical T stage or N stage by EUS (P = 0.81) or in the utilization of neoadjuvant therapy in the LTS versus STS (58% vs. 62%, respectively, P = 0.36). The LTS group was significantly more likely to have pathologic complete response (69% vs. 41%, P < 0.001), lower pathologic T stage, i.e., pT0, pTis, or pT1 (83% vs. 45%, P < 0.001), pN0 stage (97% vs. 68%, P < 0.001), favorable tumor differentiation (well or well to moderate, 39% vs. 13%, P < 0.001), and absence of angiolymphatic (88% vs. 69%, P < 0.01) or perineural invasion (95% vs. 83%, P = 0.04). In comparing the factors predictive of outcome in LTS versus the STS with increasing relative risk, absence of perineural invasion (RR 0.41 (0.27, 0.61)), negative margins (RR 0.41 (0.29, 0.57)), absence of angiolymphatic invasion (RR 0.39 (0.30, 0.51)), pN0 stage (RR 1.37 (1.23, 1.52)), pT0 or pT1 (RR 1.85 (1.64, 2.07)), pathologic complete response (RR 2.02 (1.76, 2.31)), and favorable tumor grade (RR 3.00 (2.49, 3.61)) were associated with improved survival. CONCLUSION: Tumor biological factors including favorable tumor grade may be the most important influence on 5 year actual survival in esophageal cancer.

Braun enteroenterostomy is associated with reduced delayed gastric emptying and early resumption of oral feeding following pancreaticoduodenectomy.

BACKGROUND AND OBJECTIVES: Morbidity rates following pancreaticoduodenectomy (PD) remain high with delayed gastric emptying (DGE) and slow resumption of oral diet contributing to increased postoperative length of stay. A Braun enteroenterostomy has been shown to decrease bile reflux following gastric resection. We hypothesize that addition of Braun enteroenterostomy during PD would reduce the sequelae of DGE. METHODS: From our PD database, patients were identified that underwent classic PD with partial gastrectomy from 2001 to 2006. All patients with reconstruction utilizing a single loop of jejunum at the University of Florida Shands Hospital were reviewed. Demographics, presenting signs and symptoms, pathologic diagnoses, and postoperative morbidity were compared in those patients undergoing reconstruction with an additional Braun enteroenterostomy (n = 70) to those not undergoing a Braun enteroenterostomy (n = 35). RESULTS: Patients undergoing a Braun had NG tubes removed earlier (Braun: 2 days, no Braun: 3 days, P = 0.002) and no significant change in postoperative vomiting (Braun: 27%, no Braun: 37%, P = 0.37) or NG tube reinsertion rates (Braun: 17%, no Braun: 29%, P = 0.21). Median postoperative day with tolerance of oral liquids (Braun: 5, no Braun: 6, P = 0.01) and solid diets (Braun: 7, no Braun: 9, P = 0.01) were significantly sooner in the Braun group. DGE defined by two criteria including the inability to have oral intake by postoperative day 10 (Braun: 10%, no Braun: 26%, P < 0.05) and the international grading criteria (grades B and C, Braun: 7% vs. no Braun: 31%, P = 0.003) were significantly reduced in those undergoing the Braun procedure. In addition, the median length of stay (Braun: 10 days, no Braun: 12 days, P < 0.05) was significantly reduced in those undergoing the Braun procedure. The rate of pancreatic anastomotic failure was similar in the two groups (Braun: 17% vs. no Braun: 14%, P = 0.79). Median bile reflux was 0% in those undergoing a Braun. CONCLUSIONS: The present study suggests that Braun enteroenterostomy can be safely performed in patients undergoing PD and may reduce the indicence of DGE and its sequelae. Further studies of Braun enteroenterostomy in larger randomized trials of patients undergoing PD are warranted.

Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1.

The role of operation in patients with Multiple Endocrine Neoplasia Type 1 (MEN-1) and Zollinger-Ellison Syndrome (ZES) is controversial. Our institutional bias for this disease has, in general, been towards aggressive imaging and operative removal of localized gastrinomas. Few studies have reported long-term outcomes in patients with MEN-1 and ZES. A single institution retrospective review of all patients with MEN-1 and ZES from 1970 to present was performed. Twelve patients were identified (median age = 37 years at diagnosis). The median follow-up was 18 years from diagnosis of ZES. Common symptoms associated with gastrinoma in these patients were diarrhea (n = 6), abdominal pain (n = 4), and nausea/vomiting (n = 4). Most commonly identified sites of gastrinoma were: pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1). Fifteen celiotomies were performed in total (median = 1; range 0-3). Operative procedures performed included: distal pancreatectomy (n = 4), acid reducing procedure (n = 4), enucleation of pancreatic gastrinoma (n = 3), duodenal resection (n = 3), pancreaticoduodenectomy (n = 1), and other (n = 7). One patient had a transient biochemical cure after operation lasting 3 years. Only one patient in this series had documented liver metastases of gastrinoma and no patients expired of metastatic gastrinoma. There was one postoperative patient death, secondary to respiratory arrest thought to be a result of aspiration or pulmonary embolus. Three patients died of nondisease related causes, and seven patients were alive at the time of last follow-up. Operations rarely result in biochemical cures in patients with MEN-1 and ZES. In our experience, resection of localized gastrinomas often did not require extended surgical resection and were associated with excellent long-term outcomes.

Reoperative surgery in sporadic Zollinger-Ellison Syndrome: longterm results.

BACKGROUND: Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES. STUDY DESIGN: We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies. RESULTS: Fifty-two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma. CONCLUSIONS: Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted.

Is there an indication for initial conservative management of pancreatic cystic lesions?

BACKGROUND: The management of small pancreatic cystic lesions presents a clinical challenge. METHODS: We reviewed our experience with 78 patients who presented with a cystic pancreatic lesion who underwent operative management between 1995 and 2005. Data on cyst characteristics were analyzed in the context of pathologic findings following resection. RESULTS: Among 78 patients, there were 55 (71%) females; median age 63 years. Patients presented with: an incidental finding (48%), pain (40%), acute pancreatitis (4%), other (8%). Operations were distal pancreatectomy (n = 47), pancreaticoduodenectomy (n = 16), and other (n = 15). Most patients had a non-malignant lesion (n = 65, 83%) (mucinous cystadenoma (n = 29), serous cystadenoma (n = 15), IPMN without invasion (n = 8), pseudocyst (n = 8), other benign (n = 5)). Malignant lesions (adenocarcinoma, neuroendocrine tumor, and other) were found in 13 patients (17%). The risk of malignancy increased with size: <3 cm (n = 25), 4%; 3-5 cm (n = 23), 13%; and >5 cm (n = 30), 30%. Pre-operative cyst fluid cytology was performed in 41 patients. The negative predictive value (NPV) of cytology for malignancy was 88% and the positive predictive value (PPV) was 80%. The NPV of CA 19-9 for malignancy was 90%; the PPV was 50%. CONCLUSIONS: Initial conservative management of small cystic pancreatic lesions may be indicated in selected patients.

Surgical management of failed endoscopic treatment of pancreatic disease.

INTRODUCTION: Endoscopic therapy of acute and chronic pancreatitis has decreased the need for operative intervention. However, a significant proportion of patients treated endoscopically require definitive surgical management for persistent symptoms. OBJECTIVE: Our aim was to determine which patients are likely to fail with endoscopic therapy, and to assess the clinical outcome of surgical management. Patients were identified using ICD-9 codes for pancreatic disease as well as CPT codes for endoscopic therapy followed by surgery. MATERIAL AND METHODS: Patients with documented acute or chronic pancreatitis treated endoscopically prior to surgical therapy were included (N = 88). The majority of patients (65%) exhibited chronic pancreatitis due to alcohol abuse. Common indicators for surgery were: persistent symptoms, anatomy not amenable to endoscopic treatment and unresolved common bile duct or pancreatic duct strictures. Surgical salvage procedures included internal drainage of a pseudocyst or an obstructed pancreatic duct (46%), debridement of peripancreatic fluid collections (25%), and pancreatic resection (31%). RESULTS: Death occurred in 3% of patients. The most common complications were hemorrhage (16%), wound infection (13%), and pulmonary complications (11%). Chronic pancreatitis with persistent symptoms is the most common reason for pancreatic surgery following endoscopic therapy. Surgical salvage therapy can largely be accomplished by drainage procedures, but pancreatic resection is common. CONCLUSION: These complex procedures can be performed with acceptable mortality but also with significant risk for morbidity.

Contemporary results with ampullectomy for 29 "benign" neoplasms of the ampulla.

BACKGROUND: Ampullectomy may be an appropriate oncologic procedure in selected patients. Sparse data exist on procedure-related complications and the relationship between histologic analysis and outcomes. STUDY DESIGN: We retrospectively reviewed our experience with ampullectomy in 29 patients with a preoperative benign histologic diagnosis over 15 years (1991 to 2006). Presenting signs, symptoms, and preoperative diagnostic studies were reviewed. Postoperative complications and followup for recurrence were recorded. The abilities of preoperative histologic biopsy, intraoperative frozen section, and final histologic analysis to guide management and predict outcomes were determined. RESULTS: Median age was 63 years. Jaundice was present in 30% of patients. Median length of hospital stay was 9 days. Forty-five percent of patients had a complication, and there was one postoperative mortality (3%). Ampullary adenomatous neoplasms were present in 89% of patients. Preoperative biopsy had complete concordance with final pathology in 76% of patients. Preoperative biopsy and intraoperative frozen section failed to identify carcinoma in four patients. Pancreaticoduodenectomy was performed within 7 days in the postoperative period in three of these patients. After ampullectomy (median followup=16 months), recurrences were identified in two patients (8%) with benign tumors. No patients with high-grade dysplasia (n=4) have had recurrence. CONCLUSIONS: Preoperative biopsy and intraoperative frozen section analysis have limitations in the management of patients undergoing ampullectomy. High-grade dysplasia on preoperative biopsy is not an absolute contraindication to ampullectomy. Morbidity of ampullectomy is significant, but longterm outcomes of this procedure, in patients without invasive malignancy, are acceptable.

Elevation of serum IgG4 in Western patients with autoimmune sclerosing pancreatocholangitis: a word of caution.

BACKGROUND: Autoimmune pancreatocholangitis is characterized by sclerosing inflammation of the biliary tree or pancreatic duct and can mimic pancreaticobiliary malignancy. Serum immunoglobin (Ig) G4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from pancreatic malignancy in the Japanese population; however, its significance in the Western population has not been well studied. METHODS: We report a retrospective analysis of 7 consecutive patients with autoimmune pancreatocholangitis and compare them to 23 patients with pancreatic malignancy. Clinical presentation, diagnostic tests, and preoperative IgG4 levels were reviewed in all patients. Presence of autoimmune pancreatocholangitis or pancreatic malignancy was determined by pathologic analysis in all patients and reviewed by a single pathologist. RESULTS: In all patients, autoimmune pancreatocholangitis manifested in a similar fashion to pancreatic malignancy. Median IgG4 levels were far lower in pancreatic cancer patients with localized, resectable disease (24 mg/dL), locally advanced disease (24 mg/dL), and metastatic disease (28 mg/dL) as compared with patients with autoimmune pancreatocholangitis (142 mg/dL, P < .05). Only one patient with pancreatic cancer had an IgG4 level that was >100 mg/dL. In contrast, all patients with autoimmune pancreatitis or cholangitis had levels >100 mg/dL. However, in five of these seven patients, IgG4 levels were below the upper limits of normal. CONCLUSIONS: Autoimmune pancreatocholangitis mimics pancreatobiliary malignancy. Serum IgG4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from malignancy in the Western population. However, absolute values seem to be lower in the United States compared with Japan. The upper limit of normal as reported in laboratories in the United States may not be useful in identifying abnormally high IgG4 values. A new upper limit of normal may need to be defined because IgG subclass determinations are being used more frequently in Western patients with biliary obstruction.

Presentation and management of gastrointestinal stromal tumors of the duodenum.

Duodenal gastrointestinal stromal tumors (GIST) have been described primarily in isolated case reports. In order to learn more about duodenal GIST, a retrospective review of patients with GIST managed at a single institution between 2000 and 2005 was conducted. Thirty-eight GIST of the stomach and small bowel were analyzed. Eight (21%) were duodenal GIST. The median size of duodenal GIST (6.0 cm) and small bowel GIST (6.3 cm) was larger than the median size of gastric GIST (3.0 cm). The most common presentation of duodenal GIST was bleeding (50%) which was similar to other small bowel GIST (49%) but different from gastric GIST which were most commonly an incidental finding (62%). Two patients (25%) with duodenal GIST had a history of neurofibromatosis. The duodenal GIST were located in the 2nd (n = 5, 63%) and 3rd portion of duodenum (n = 3, 37%). Seven of 8 patients underwent complete resection of duodenal GIST. Pancreaticoduodenectomy was the most common operation performed (n = 5); 2 patients were treated with partial duodenal resection. No patients undergoing pancreaticoduodenectomy (n = 5) were found to have lymph node metastases. No patients received neo-adjuvant or adjuvant therapy with Imatinib. Following resection, 2 patients have recurred (12 and 48 mo.), 4 patients are without disease (1, 6, 6, and 24 mo.), 1 patient died postoperatively. Duodenal GIST are relatively rare tumors that present most commonly with gastrointestinal bleeding. Duodenal GIST are associated with neurofibromatosis. Many duodenal GIST require pancreaticoduodenectomy for complete removal.

Esophageal perforation in adults: aggressive, conservative treatment lowers morbidity and mortality.

OBJECTIVE: To evaluate the outcome of aggressive conservative therapy in patients with esophageal perforation. SUMMARY BACKGROUND DATA: The treatment of esophageal perforation remains controversial with a bias toward early primary repair, resection, and/or proximal diversion. This review evaluates an alternate approach with a bias toward aggressive drainage of fluid collections and frequent CT and gastographin UGI examinations to evaluate progress. METHODS: From 1992 to 2004, 47 patients with esophageal perforation (10 proximal, 37 thoracic) were treated (18 patients early [<24 hours], 29 late). There were 31 male and 16 females (ages 18-90 years). The etiology was iatrogenic (25), spontaneous (14), trauma (3), dissecting thoracic aneurysm (3), and 1 each following a Stretta procedure and Blakemore tube placement. RESULTS: Six of 10 cervical perforations underwent surgery (3 primary repair, 3 abscess drainage). Nine of 10 perforations healed at discharge. In 37 thoracic perforations, 2 underwent primary repair (1 iatrogenic, 1 spontaneous) and 4 underwent limited thoracotomy. Thirty-4 patients (4 cervical, 28 thoracic) underwent nonoperative treatment. Thirteen of the 14 patients with spontaneous perforation (thoracic) underwent initial nonoperative care. Overall mortality was 4.2% (2 of 47 patients). These deaths represent 2 of 37 thoracic perforations (5.4%). There were no deaths in the 34 patients treated nonoperatively. Esophageal healing occurred in 43 of 45 surviving patients (96%). Subsequent operations included colon interposition in 2, esophagectomy for malignancy in 3, and esophagectomy for benign stricture in 2. CONCLUSIONS: Aggressive treatment of sepsis and control of esophageal leaks leak lowers mortality and morbidity, allow esophageal healing, and avoid major surgery in most patients.

Blind Whipple resections for periampullary and pancreatic lesions.

Many patients with periampullary mass lesions lack a tissue diagnosis at referral despite advances in body imaging and aggressive biopsy techniques. This review evaluates a consecutive cohort of patients who underwent pancreatoduodenectomy (PD) with and without a diagnosis of malignancy. From 1990 to 2001, 121 patients underwent PD on a gastrointestinal surgical service by a single surgeon with a bias toward "blind" Whipple resections (BWR). Sixty-three per cent of the patients had obstructive jaundice with a mass on CT in 51 per cent. Fifty-three patients (44%) had a preoperative diagnosis of malignancy. Sixty-eight patients (56%) underwent a blind PD based on computed tomography (CT), ERCP, and clinical findings. After PD, 113 patients (94%) had a malignancy (46 pancreatic, 30 ampullary, 13 cholangiocarcinoma, 9 neuroendocrine, 4 duodenal, 10 other). Of the 68 patients (56%) who underwent a blind PD, 61 patients (90%) had a malignancy. Ten per cent of the BWR patients had a pathologic diagnosis of chronic inflammation/pancreatitis. Overall mortality was 3.3% (4 patients), with no deaths in the BWR group. In this review, clinical judgment was correct in 90 per cent of patients undergoing a "blind" PD without a prior diagnosis of malignancy. In patients with "potentially resectable" lesions (based on CT exam), biopsy information does not affect the choice of therapy since a negative biopsy still commits the patients to surgery. Combined CT and/or ERCP data with clinical findings leads most often to a correct diagnosis and procedure. These data question the practice of numerous biopsy attempts in patients with periampullary lesions.

Dual-radionuclide simultaneous biliary and gastric scintigraphy to depict surgical treatment of bile reflux.

Biliary diversion procedures are performed during gastric surgery to decrease bile reflux. A 1-day dual-radionuclide examination was studied to determine its potential in the evaluation of the effectiveness of the Braun enteroenterostomy in reducing bile reflux and its effects on gastric emptying. Orally ingested gallium 67-labeled egg and intravenously administered technetium 99m diisopropyl-imino-diacetic acid were imaged simultaneously. This provided a way to depict both bile reflux and gastric emptying on the same day in patients who underwent gastric surgery. Overall, the Braun enteroenterostomy trades bile reflux, a symptomatic and premalignant disease, for gastroparesis, a less severe and often treatable disease.

Factors predictive of survival for esophageal carcinoma treated with preoperative radiotherapy with or without chemotherapy followed by surgery.

PURPOSE: To evaluate parameters that may influence prognosis in patients treated with preoperative radiotherapy (RT) or chemoradiation. METHODS AND MATERIALS: One hundred seventy-six patients with esophageal carcinoma received preoperative radiotherapy (45 patients) or chemoradiation (131 patients). Forty-three received no surgery (NS), 32 had exploratory surgery (ES), and 101 received definitive surgery (DS). RESULTS: Five-year cause-specific survival and absolute survival rates were overall, 19% and 16%; NS group, 0% and 0%; ES group, 3% and 3%; DS group, 30% and 26%. On univariate analysis, definitive surgery (P < 0.0001), tumor size less than 5 cm (P < 0.0001), and chemotherapy (P = 0.0015) were significant predictors of improved cause-specific survival. Cause-specific survival was 51% for tumors /=6 cm (n = 86) survived. Multivariate analysis of the DS group showed complete or partial pathologic response (P = 0.0001), chemotherapy (P = 0.0026), and overall treatment time less than 3 months (P = 0.0405) significantly predicted improved cause-specific survival. Tumor <5 cm was marginally significant (P = 0.0515). CONCLUSION: Patients who undergo preoperative chemoradiation and definitive surgery have improved survival.

Role of endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration in the diagnosis and treatment of cystic lesions of the pancreas.

INTRODUCTION AND AIMS: Cystic neoplasms of the pancreas may be inadvertently treated as benign pseudocysts in clinical practice, often without the use of cytology, cyst tumor markers, or histopathology. We assessed the utility of EUS-guided fine-needle aspiration (EUS-FNA) to assist in the diagnosis and management of pancreatic cysts. METHODOLOGY: All patients who had pancreatic cysts detected by EUS over a 24-month period were analyzed. Preoperative diagnosis was derived from an algorithm combining clinical history and endosonographic features. In selected cases, EUS-FNA was performed and cyst fluid aspirates were analyzed. Surgical specimens served as diagnostic standard. RESULTS: A total of 43 patients with pancreatic cysts underwent 45 EUS examinations. Surgical specimens were obtained from 9 patients (mucinous cystadenocarcinoma, 3; adenocarcinoma, 3; pancreatic endocrine tumor, 2; and benign cyst, 1); diagnostic EUS correctly predicted malignant cysts in 8/9 (88.9%). One case inaccurately interpreted by EUS as cystic neoplasm turned out to be a benign cyst on resection. Twenty-one patients underwent EUS-FNA. The cytologic interpretation was adenocarcinoma in 9.5% (2/21); suspicious for malignancy or atypical cells in 19.0% (4/21); benign in 66.6% (14/21); and insufficient cells in 4.8% (1/21). CONCLUSION: The information gathered from clinical history and EUS, complemented by fluid analysis after EUS-guided FNA, predicts neoplastic pancreatic cysts and assists in decision-making for medical or surgical approach.

Gallium uptake in complicated pancreatitis: a predictor of infection.

OBJECTIVE: A retrospective evaluation was performed of the use of gallium imaging in patients with known severe pancreatitis to detect infection in pancreatic and peripancreatic fluid collections. MATERIALS AND METHODS: Gallium-67 single-photon emission computed tomography (SPECT) studies were retrospectively reviewed in patients with complicated pancreatitis. Only patients who had undergone interventional procedures within 10 days of the scanning were included in our analysis. A total of 23 scans from 20 patients were reviewed. SPECT imaging was typically performed 48-72 hr after injection of the gallium. All studies were correlated with conventional CT findings. Findings from subsequent interventions (results of aspiration, Gram stains, or cultures) were used as evidence of infection. RESULTS: Twenty patients underwent either percutaneous or surgical drainage within 10 days of their gallium scanning. One patient underwent gallium scanning on three different occasions and underwent three different interventional procedures after each of the gallium scans, bringing the total number of cases in our study to 23. Of these 23 cases, 18 patients (78%) with gallium scans showing positive findings for infection had infected fluid; five patients (22%) with negative findings for infection on gallium scans had sterile fluid (p < 0.00001). No false-positive scans were found among our study cases, and we found no correlation between the uptake of gallium and the presence or absence of pancreatic necrosis. CONCLUSION: Gallium does not actively accumulate in all patients with severe pancreatitis, and gallium uptake does not correlate with the presence or absence of necrosis. In patients with severe pancreatitis complicated by fluid collections or inflammatory masses, gallium SPECT is a useful predictor of infection and can be used to help guide subsequent intervention. Gallium SPECT allows targeting sites of infected fluid in patients with multiple fluid collections and potentially obviates intervention in patients with sterile fluid collections.