Stephen B. Vogel

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.

Results of a Randomized Trial Comparing Sequential Intravenous/ Oral Treatment with Ciprofloxacin Plus Metronidazole to Imipenem/ Cilastatin for Intra-Abdominal Infections

OBJECTIVE In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. CONCLUSIONS These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.

Definition of the role of enterococcus in intraabdominal infection: Analysis of a prospective randomized trial

BACKGROUND The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial. METHODS A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America. RESULTS In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation. CONCLUSIONS This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

Proposed revision of the esophageal cancer staging system to accommodate pathologic response (PP) following preoperative chemoradiation (CRT)

Objective:To determine the impact of pathologic response following preoperative chemoradiation (CRT) on the AJCC esophageal cancer staging system. Summary Background Data:Increasing numbers of locoregionally advanced esophageal cancer patients are treated with preoperative CRT prior to surgical resection. Methods:Five hundred ninety-three pts from 1985 to 2003 with esophageal cancer who underwent surgery with (n = 239) or without CRT (n = 354) were reviewed. Resected esophageal tumors were assessed for pathologic response by determining extent of residual tumor following CRT (P0, 0% residual; P1, 1%–50% residual; P2, >50% residual). Results:After CRT down-staging, pTNM specific survival was similar, irrespective of treatment group (P = 0.98). The pTNM stage distribution was more favorable in the CRT group (P < 0.001) despite a more advanced initial cTNM stage distribution (P < 0.001). Following CRT, the pathologic response (pP) at the primary tumor as defined by extent of residual tumor predicted overall survival (3 years: P0, 0% residual = 74%; P1, 1%–50% residual = 54%; P2, >50% residual = 24%, P < 0.001) and stage specific survival with greater accuracy than pTNM stage alone. Conclusions:Our analyses demonstrate that following CRT, pTNM continues to predict survival. The extent of pathologic response following CRT is an independent risk factor for survival (pP) and should be incorporated in the pTNM esophageal cancer staging system to better predict patient outcome in esophageal cancer.

Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing

Postoperative gastric myoelectric activity, gastric emptying, and clinical course were correlated in 17 patients at high risk of developing gastroparesis after gastric surgery. In addition, an attempt was made to pace the stomach with an electrical stimulus and determine the effect of pacing on early postoperative gastric emptying. Gastric dysrhythmias (bradygastria, slow wave frequency < 2 cycles/min; tachygastria, slow wave frequency > 4 cycles/min) persisted beyond the first postoperative day in 6 patients (35%). Delayed gastric emptying was identified by a radionuclide meal in 15 patients (88%), but symptoms of gastroparesis developed in only 6 of 15 (40%). Patients with postoperative gastroparesis had more frequent dysrhythmias than asymptomatic patients (67% vs. 18%), but these differences were not significant, although we cannot exclude a type II statistical error. Gastric rhythm was entrained in 10 of 16 patients (63%). Pacing increased the gastric slow wave frequency (3.1 vs. 4.1 cycles/min; P < 0.01) but did not improve gastric emptying (gastric retention at 60 minutes, 86% +/- 6% for control and 90% +/- 2% for paced). In conclusion, gastric dysrhythmias do not appear to play a major role in the development of postsurgical gastroparesis. Although gastric rhythm could be entrained in the majority of patients, pacing did not improve gastric emptying overall.

Downstaging of esophageal cancer after preoperative radiation and chemotherapy

ObjectiveThis retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. MethodsForty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent “potentially curative” resections–transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. ResultsThere were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1− and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5-year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). ConclusionAlthough retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics.

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.

Central venous catheter vascular erosions. Diagnosis and clinical course.

Central venous catheter (CVC) vascular erosions are difficult to diagnose, and they cause serious complications. From 1985 to 1987, ten patients receiving the surgical services at the University of Florida suffered CVC vascular erosions. By chest roentgenogram, nine CVC tips were in the superior vena cava (SVC), although three catheter tips abutted the lateral wall of the SVC. One catheter tip was in the right atrium. All patients had sudden onset of symptoms, the most common of which was shortness of breath. Initial diagnosis was respiratory insufficiency in five patients, cardiac failure in three patients, pulmonary embolism in one, and sepsis in one. Four patients required intensive care. Two patients suffered pericardial tamponade, and pleural effusions developed in eight patients. One patient died of cardiac arrest. The average time interval from CVC placement to onset of symptoms was 60.2 hours, and from the onset of symptoms to the time of diagnosis, the interval was 16.7 hours. The mean volume obtained at thoracentesis was 1324 ml and at pericardiocentesis was 250 ml.

Esophageal cancer—the five year survivors

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.

Diagnosis of pancreatic cancer and prediction of unresectability using the tumor-associated antigen CA19-9

Marked elevations of the tumor-associated antigen CA19-9 are relatively specific for pancreatic carcinoma and are associated with more advanced malignancies. We retrospectively reviewed 53 patients with CA19-9 values >90 U/ml in whom the test had been done because of clinical suspicion of pancreatic malignancy. Pancreatic cancer was found in 45 patients (85%). If a cutoff value of CA19-9 >200 U/ml is used, 36 of 37 (97%) patients had pancreatic cancer. Thirty patients with pancreatic cancer and no radiographic criteria of unresectability underwent attempted resection; five of these patients were judged to be potentially resectable and four of them underwent attempted resection. In only one patient with a CA19-9 value >300 U/ml was resection possible; this patient had advanced carcinoma. Our results suggest that, in patients in whom the clinician suspects pancreatic carcinoma, CA19-9 >90 U/ml is highly suggestive of pancreatic malignancy, while CA19-9 >200 U/ml is virtually diagnostic of pancreatic malignancy. In similar patients with CA19-9 >300 U/ml, resection is rarely possible and tumors are advanced.