Showing papers in "Annals of Surgery in 1992"

Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

Abstract: This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

Multiple organ failure. Pathophysiology and potential future therapy.

Abstract: Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome.

Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma.

Abstract: To investigate the importance of route of nutrient administration on septic complications after blunt and penetrating trauma, 98 patients with an abdominal trauma index of at least 15 were randomized to either enteral or parenteral feeding within 24 hours of injury. Septic morbidity was defined as pneumonia, intra-abdominal abscess, empyema, line sepsis, or fasciitis with wound dehiscence. Patients were fed formulas with almost identical amounts of fat, carbohydrate, and protein. Two patients died early in the study. The enteral group sustained significantly fewer pneumonias (11.8% versus total parenteral nutrition 31.%, p less than 0.02), intra-abdominal abscess (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and line sepsis (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and sustained significantly fewer infections per patient (p less than 0.03), as well as significantly fewer infections per infected patient (p less than 0.05). Although there were no differences in infection rates in patients with injury severity score less than 20 or abdominal trauma index less than or equal to 24, there were significantly fewer infections in patients with an injury severity score greater than 20 (p less than 0.002) and abdominal trauma index greater than 24 (p less than 0.005). Enteral feeding produced significantly fewer infections in the penetrating group (p less than 0.05) and barely missed the statistical significance in the blunt-injured patients (p = 0.08). In the subpopulation of patients requiring more than 20 units of blood, sustaining an abdominal trauma index greater than 40 or requiring reoperation within 72 hours, there were significantly fewer infections per patient (p = 0.03) and significantly fewer infections per infected patient (p less than 0.01). There is a significantly lower incidence of septic morbidity in patients fed enterally after blunt and penetrating trauma, with most of the significant changes occurring in the more severely injured patients. The authors recommend that the surgeon obtain enteral access at the time of initial celiotomy to assure an opportunity for enteral delivery of nutrients, particularly in the most severely injured patients.

Cytokine serum level during severe sepsis in human IL-6 as a marker of severity.

Abstract: Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit. Among these patients, 19 developed septic shock and 16 died, 9 of them from septic shock. Interleukin 1 beta (IL-1 beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every 1 or 2 hours when septic shock occurred. Although IL-1 beta was never found, TNF alpha was most often observed in the serum at a level under 100 pg/mL except during septic shock. During these acute episodes TNF alpha level reached several hundred pg/mL, but only for a few hours. In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/mL). There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level. Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above 1000 pg/mL. Thus, IL-6 appears to be a good marker of severity during bacterial infection.

A better model of acute pancreatitis for evaluating therapy.

Abstract: Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Management strategies in resection for hilar cholangiocarcinoma.

Abstract: Between 1960 and 1990, resection was performed in 23 of 122 patients who underwent surgical treatment for hilar cholangiocarcinoma. Local excision of the lesion alone was performed in 10 cases (43%). Hepatic resection for tumor extending to the secondary bile ducts or hepatic parenchyma was performed in 13 cases (57%): extended right hepatectomy (3), right hepatectomy (1), extended left hepatectomy (6), left hepatectomy (2), and left lobectectomy (1). In three other cases, resection by total hepatectomy and liver transplantation was performed, but these were not included in the analysis of results for resection. Significant operative complications occurred in only two cases (8.7%), and the operative mortality rate was zero. In four cases, complete excision of the tumor could not be achieved macroscopically (macroscopic curative resection rate 19/122; 15.6%). In nine cases, the margins of the resected specimens were free from tumor on histologic examination (microscopic curative resection rate, 9/122; 7.4%). In 10 cases, the resection margins were found to contain tumor on histologic examination. The overall survival rate was 87% at 1 year, 63% at 2 years, and 25% at 3 years (median survival, 24 months). The survival and freedom from recurrence rates for patients with free resection margins was superior to that for patients with involved resection margins or residual macroscopic disease. A potentially curative resection, with histologically negative margins and no recurrence to date, was achieved in seven patients using the following procedures: local excision for two type I lesions; left hepatectomy plus excision of segment 1 for two type IIIb lesions and one type IV lesion; right hepatectomy and right hepatectomy plus excision of segment 1 for two type IIIa lesions. These results indicate that improved survival in hilar cholangiocarcinoma can be achieved by resection, with minimal morbidity and zero mortality rates, if histologically free resection margins are obtained. To achieve this, we recommend the following procedures for each type of lesion, based on our experience and on anatomic considerations: local excision for type I; local excision plus resection of segment 1 for type II; local excision, resection of segment 1, and right or left hepatectomy for types IIIa and b; hepatectomy plus liver transplantation for type IV.

Abbreviated laparotomy and planned reoperation for critically injured patients.

Abstract: The triad of hypothermia, acidosis, and coagulopathy in critically injured patients is a vicious cycle that, if uninterrupted, is rapidly fatal. During the past 7.5 years, 200 patients were treated with unorthodox techniques to abruptly terminate the laparotomy and break the cycle. One hundred seventy patients (85%) suffered penetrating injuries and 30 (15%) were victims of blunt trauma. The mean Revised Trauma Score, Injury Severity Score, and Trauma Index Severity Score age combination index predicted survival were 5.06%, 33.2%, and 57%, respectively. Resuscitative thoracotomies were performed in 60 (30%) patients. After major sources of hemorrhage were controlled, the following clinical and laboratory mean values were observed: red cell transfusions--22 units, core temperature--32.1 C, and pH--7.09. Techniques to abbreviate the operation included the ligation of enteric injuries in 34 patients, retained vascular clamps in 13, temporary intravascular shunts in four, packing of diffusely bleeding surfaces in 171, and the use of multiple towel clips to close only the skin of the abdominal wall in 178. Patients then were transported to the surgical intensive care unit for vigorous correction of metabolic derangements and coagulopathies. Ninety-eight patients (49%) survived to undergo planned reoperation (mean delay 48.1 hours), and 66 of 98 (67%) survived to leave the hospital. With the exception of intravascular shunts, there were survivors who were treated by each of the unorthodox techniques. Of 102 patients who died before reoperation 68 (67%) did so within 2 hours of the initial procedure. Logistic regression showed that red cell transfusion rate and pH may be helpful in determining when to consider abbreviated laparotomy. The authors conclude that patients with hypothermia, acidosis, and coagulopathy are at high risk for imminent death, and that prompt termination of laparotomy with the use of the above techniques is a rational approach to an apparently hopeless situation.

Mechanisms of major biliary injury during laparoscopic cholecystectomy.

Abstract: Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. The most significant complication of this new technique is injury to the bile duct. Twelve cases of bile duct injury during laparoscopic cholecystectomy were reviewed. Eight injuries were of a classic type: misidentification of the common duct for the cystic duct, resection of part of the common and hepatic ducts, and associated right hepatic arterial injury. Another injury was similar: clip ligation of the distal common duct with proximal ligation and division of the cystic duct, resulting in biliary obstruction and leakage. Three complications arose from excessive use of cautery or laser in the region of the common duct, resulting in biliary strictures. Evaluation of persistent diffuse abdominal pain led to the recognition of ductal injury in most patients. Ultimately, 10 patients required a Roux-en-Y hepaticojejunostomy to provide adequate biliary drainage. One patient had a successful direct common duct repair, and the remaining patient underwent endoscopic dilatation.

Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma.

Abstract: The authors reviewed their institutional experience with liver resection for metastatic colorectal carcinoma to (1) determine whether perioperative blood transfusion affects survival; (2) identify prognostic determinants; and (3) estimate the patient requirement for a prospective randomized trial designed to demonstrate efficacy of liver resection. Two hundred eighty consecutive patients treated by potentially curative liver resection between 1960 and 1987 were included. Data were obtained for all but 10 patients for at least 5 years after operation or through 1990. Actuarial survival curves related to potential prognostic determinants were analyzed with the log-rank test. Overall, survival was 47 +/- 3% at 3 years and 25 +/- 3% at 5 years, including 4% 60-day operative mortality rate. Eighty-one patients who did not receive blood 7 days before to 14 days after operation had 60 +/- 6% 3-year and 32 +/- 6% 5-year survival compared with 40 +/- 4% and 21 +/- 3% survival rates for 183 patients who received at least one unit (p = 0.03, operative deaths excluded). Extrahepatic disease (p = 0.015), extrahepatic lymph node involvement (p = 0.002), satellite configuration of multiple metastases (p = 0.0052), and initial detection by abnormal liver enzymes (p = 0.0005) were associated with poor survival rates. Synchronous presentation of metastatic and stage B primary disease was associated with a favorable prognosis (p = 0.003). The requirement for a prospective randomized trial estimated by an exponential survival model would be 36, 74, 168, or 428 patients if 5-year survival without resection were 1, 5, 10, or 15%. We conclude that (1) perioperative blood transfusion may be adversely associated with survival; (2) extrahepatic disease, extrahepatic lymph node involvement, satellite configuration, and initial detection by clinical examination or a liver enzyme abnormality portend a poor prognosis; and (3) a prospective randomized trial of liver resection is impractical because of the large patient requirement, at least by a single institution.

Long-limb gastric bypass in the superobese. A prospective randomized study.

Abstract: This study was designed to determine whether greater diversion of bile and pancreatic secretions away from the functional gastrointestinal tract would produce greater weight loss in superobese patients (greater than or equal to 200 pounds overweight) in comparison with conventional Roux-en-Y gastric bypass (RYGB). During the past 7 years, two modifications of RYGB were prospectively compared in 45 superobese patients: RYGB-1, in which the length of defunctionalized jejunum measured 75 cm, and RYGB-2, in which the defunctionalized jejunum measured 150 cm. Respective mean preoperative weight/body mass indexes were 393 pounds/63.4 for 22 RYGB-1 patients and 404 pounds/61.6 for 23 RYGB-2 patients. Two patients (5%) had nonfatal early complications. There were six late incisional hernias. There were no cases of protein deficiency, hepatic dysfunction, or diarrhea after operation. Mean follow-up was 43 +/- 17 months. Postoperative weight loss in pounds and daily calorie intake were compared at 6-month intervals. Weight loss stabilized by 24 months at a mean 50% excess weight lost in RYGB-1 patients and 64% excess weight lost in RYGB-2 patients. Nineteen of 23 RYGB-2 patients achieved at least 50% excess weight lost versus 11 of 22 RYGB-1 patients (p less than or equal to 0.03). Weight loss was significantly greater at 24 through 36 months in RYGB-2 versus RYGB-1 patients (p less than 0.02). There was no significant difference in either calorie intake or incidence of iron and vitamin B-12 deficiency between the two groups. These data show that gastric restriction and biliopancreatic diversion without intestinal exclusion resulted in significantly greater weight loss than conventional RYGB but did not cause additional metabolic sequelae or diarrhea. This long-limb modification of Roux-en-Y gastric bypass is a safe and effective procedure in patients who are 200 pounds or more overweight.

Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine.

Abstract: A new polyvalent melanoma cell vaccine (MCV) was administered to 136 stage IIIA and IV (American Joint Committee on Cancer) melanoma patients. Induction of cell-mediated and humoral immune responses to common melanoma-associated antigens present on autologous melanoma cells was observed in patients receiving the new MCV. This was accompanied by increased activation of tumor-infiltrating lymphocytes. Survival correlated significantly with delayed cutaneous hypersensitivity (p = 0.0066) and antibody responses to MCV (p = 0.0117). Of 40 patients with evaluable disease, nine (23%) had regressions (three complete). From our historical database of 126 stage IIIA and 1275 stage IV melanoma patients, there were no significant changes in the natural history of metastatic melanoma during the past 20 years. Univariate and multivariate analyses demonstrated prognostic significance for site of metastases (p = 0.0001) and immunotherapy with the new MCV (p = 0.0001). Overall our new MCV increased the median and 5-year survival of stage IIIA melanoma patients with regional soft tissue metastases twofold (p = 0.00024), and stage IV patients threefold (p = 0.0001) compared with previous immunotherapy and other treatments.

Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging.

Abstract: The appropriate surgical therapeutic options for either localized or more advanced disease in patients with gastrointestinal leiomyosarcomas remain unclear. A staging classification for this disease has not been adopted nor risk factors identifying patients at risk for recurrence defined. To address these issues, this study evaluated the influence of various clinicopathologic variables on overall and disease-free survival. In an univariate analysis of overall survival involving 191 patients, the Cox proportional hazards model identified four factors that were associated with a significantly better outcome: complete resection without tumor rupture (p less than 0.001), localized lesions (p less than 0.001), low grade of tumor (p = 0.02), and tumors smaller than 5 cm (p = 0.03). When interactive effects of these factors were taken into account, however, type of resection of the tumor was selected as the only significant prognostic factor in a multivariate analysis. Complete resection without tumor rupture improved overall survival of patients with localized disease (median, 46 months) as well as those with contiguous organ invasion (median, 36 months) or peritoneal implants (median, 36 months). In contrast, patients with incomplete resections survived for a median of 21 months. Patients with tumor rupture, despite removal of all gross disease, behaved similarly to those with incomplete resections; median survival was only 17 months. For disease-free survival, important determinants selected from a multivariate analysis were tumor rupture (p = 0.002), contiguous organ invasion (p = 0.02) and high tumor grade (p = 0.02). A staging classification incorporating these prognostic factors of significance was evaluated using a TGM system: T1 (less than 5 cm), T2 (greater than or equal to 5 cm), T3 (contiguous organ invasion or peritoneal implants), T4 (tumor rupture); G: G1 (low grade), G2 (high grade); M: M0 (no metastases), M1 (metastases present). The corresponding 5-year overall survivals for stages I, II, III, IVA, and IVB were 75%, 52%, 28%, 12%, and 7%. Disease-free survival at 2 years after surgery was 89%, 57%, and 47% for stages I, II, and III, respectively. In conclusion, surgery remains the primary modality of treatment for patients with gastrointestinal leiomyosarcomas, and complete resection of all disease without tumor rupture, even of locally advanced disease, improves overall and disease-free survival. A staging classification appears feasible and is recommended to determine outcome in patients with leiomyosarcomas arising from the gastrointestinal tract.

Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease.

Abstract: Many advances have occurred in recent years in the diagnosis, localization, and treatment of primary hyperparathyroidism. Several different operative choices for primary hyperparathyroidism also have been proposed--a unilateral approach versus the standard bilateral parathyroid exploration. The unilateral approach is based on the concept that if an enlarged parathyroid gland and a normal gland are found on the first side of the neck that is explored, then this is an adenoma and the second side should not be explored. Only if both glands on the initial side are recognized to be abnormal is the second side explored. The theoretical advantages of this unilateral approach are a decrease in operative morbidity rates--hypoparathyroidism and nerve injuries--and a decrease in operative time. Furthermore, proponents argue that if persistent hyperparathyroidism occurs, the second side can be easily explored because it was previously untouched. In the hands of several expert parathyroid surgeons, excellent results have been achieved. However, the unilateral approach has a number of disadvantages. It places considerable pressure on the surgeon and pathologist, for they have only one parathyroid gland other than the large one to examine. There is a significant potential risk of missing double adenomas or asymmetric hyperplasia because the second, ipsilateral parathyroid gland may appear normal or near normal in these conditions. This could lead to an increased incidence of persistent or recurrent hyperparathyroidism. Furthermore, a significant reduction of operative time may be questioned, especially when the time for performing special fat stains, which often are performed with unilateral explorations, is added. Finally, even if the intent is to perform a unilateral exploration, a bilateral exploration will be necessary about half of the time. The authors strongly recommend a bilateral parathyroid exploration for all patients undergoing an initial parathyroid operation. In cases of adenoma, bilateral visualization of normal parathyroid glands and careful biopsy of only one of them will minimize hypoparathyroidism. This operative approach will lead to better results, especially for the less experienced parathyroid surgeon.

Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy.

Abstract: From 1975 through 1988, 257 patients with carcinoma of the thoracic esophagus have been treated in our department. Operability was 90% (232/257); overall resectability, 77% (198/257), and for the operated group, 85% (198/232). Hospital mortality rate was 9.6% but decreased to 3% over the period 1986 to 1988. There were 65% squamous cell epitheliomas and 35% adenocarcinomas. Tumor, nodes, and metastases (pTNM) staging was as follows: stage I, 11.6%; stage II, 23.2%; stage III, 37.9%; stage IV, 27.3%. Overall survival rate was 62.5% at 1 year, 42.4% at 2 years, and 30% at 5 years. According to the pTNM staging, 5-year survival was 90% for stage I, 56% for stage II, 15.3% for stage III, and 0 for stage IV. There were no statistically significant differences according to tumor localization, pathologic type, sex, or age. Introducing extensive resection and extended lymphadenectomy seems to improve significantly survival in patients in whom an operation with curative intention was performed, the 1 year survival rate being 90.8% versus 72%; 2-year survival, 81% versus 46%; and 5-year survival, 48.5% versus 41% for radical and nonradical resections, respectively. Based on multivariate Cox regression analysis, only TNM stage and presence or absence of lymph nodes are important factors in predicting survival: stage 1 tumors have lower risk, and involvement of lymph nodes creates higher risk. Using this analysis, there was only for the patients with involved lymph nodes (N1) a significantly better prognosis when a radical lymph node dissection was performed (p = 0.0055). Barrett adenocarcinomas have no worse prognosis than other esophageal carcinomas, with a 5-year survival rate of 91.5% if lymph nodes are negative, and a 54% overall 5-year survival rate. Functional results after restoration of continuity with gastric tubulation were judged excellent to very good in 86.5% at 1 year, but infra-aortic anastomoses have a much higher incidence of peptic esophagitis: 53% versus 8% for cervical anastomoses. From this study it can be concluded that in experienced hands surgery today offers the best chances for optimal staging, potential cure, and prolonged high-quality palliation.

Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia.

Abstract: The authors treated 17 patients with achalasia by a thoracoscopic (15 patients) or laparoscopic (2 patients) Heller myotomy. All patients had dysphagia and an upper gastrointestinal series demonstrating a dilated esophagus with a bird-beak deformity at the cardia. Manometry showed a mean lower esophageal sphincter (LES) pressure of 32 +/- 4 mmHg, incomplete sphincter relaxation on swallowing, and no primary esophageal peristalsis. After operation, mean LES pressure was 10 +/- 2 mmHg. Fifteen patients were fed on the second postoperative day. The average hospital stay was 3 days, and there were no deaths or major complications. In three early patients, the myotomy was not carried far enough onto the stomach, and dysphagia persisted until a second myotomy was performed (laparoscopically in two patients). The authors found that having an endoscope in the esophagus during the operation facilitated exposure and was vital to determine the appropriate length of the myotomy. With regard to dysphagia, final results were excellent in 12 patients (70%), good in two patients (12%), fair in two patients (12%), and poor in one patient (6%). Heller myotomy can be safely and reliably performed with minimally invasive techniques. Dysphagia is relieved, postoperative pain is minimal, hospital stay is short, and the patient can return quickly to normal activity.

Inapparent carcinoma of the gallbladder. An appraisal of a radical second operation after simple cholecystectomy.

Abstract: This study was designed to investigate issues concerning "inapparent carcinoma" of the gallbladder and the effectiveness of a radical second operation in the treatment of inapparent carcinoma. Ninety-eight patients with inapparent carcinoma were analyzed according to the "pT" category of TNM (tumor, nodes, and metastases) classification. Eighty patients underwent cholecystectomy alone, and 14 patients had a subsequent radical operation. After cholecystectomy alone it was found that (1) Patients with pT1 cancer had a 5-year survival rate (5ysr) of 100%; (2) In patients with pT2, 5ysr was 40%; and (3) Patients with pT3 showed 5ysr of 0%. Results of a radical second operation showed that (1) Patients with pT2 cancer showed a 5ysr of 90%, significantly better (p less than 0.05) than pT2 treated with cholecystectomy alone; (2) There was a prolongation of survival in patients with pT3 or pT4. It was concluded that a radical second operation should be carried out for pT2 or more advanced inapparent carcinoma, whereas follow-up without a second operation is recommended for pT1 cancer without positive margin.

The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores.

Abstract: The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p 70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds.

Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux.

Abstract: The factors contributing to the development of esophageal mucosal injury in gastroesophageal reflux disease (GERD) are unclear. The lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and the presence of excessive duodenogastric reflux (DGR) was evaluated in 205 consecutive patients with GERD and various degrees of mucosal injury (no mucosal injury, n = 92; esophagitis, n = 66; stricture, n = 19; Barrett's esophagus, n = 28). Manometry and 24-hour esophageal pH monitoring showed that the prevalence and severity of esophageal mucosal injury was higher in patients with a mechanically defective lower esophageal sphincter (p less than 0.01) or increased esophageal acid/alkaline exposure (p less than 0.01) as compared with those with a normal sphincter or only increased esophageal acid exposure. Complications of GERD were particularly frequent and severe in patients who had a combination of a defective sphincter and increased esophageal acid/alkaline exposure (p less than 0.01). Combined esophageal and gastric pH monitoring showed that esophageal alkaline exposure was increased only in GERD patients with DGR (p less than 0.05) and that DGR was more frequent in GERD patients with a stricture or Barrett's esophagus. A mechanically defective lower esophageal sphincter and reflux of acid gastric juice contaminated with duodenal contents therefore appear to be the most important determinants for the development of mucosal injury in GERD. This explains why some patients fail medical therapy and supports the surgical reconstruction of the defective sphincter as the most effective therapy.

Glutamine preserves liver glutathione after lethal hepatic injury.

Abstract: Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. Glutamine augments host defenses and may be important in GSH synthesis. Acetaminophen toxicity causes hepatic GSH depletion and hepatic necrosis. The authors hypothesized that glutamine-supplemented nutrition would enhance liver GSH stores and diminish hepatic injury and death after acetaminophen overdose. Wistar rats received either a standard total parenteral nutrition (TPN) solution (STD) or an isocaloric, isonitrogenous glutamine-supplemented solution (GLN). On the 5th day of feeding, animals were given acetaminophen (400 mg/kg intraperitoneally) and then killed at various time points. Standard TPN solution animals had a rapid depletion of hepatic glutathione, whereas GLN animals were resistant to this drop and rapidly repleted hepatic GSH stores. Glutamine-supplemented animals maintained higher plasma glutamine concentrations, had lesser elevations in hepatic enzymes, and sustained significantly fewer complications compared with STD animals. The authors conclude that glutamine-supplemented nutrition preserves hepatic glutathione, protects the liver, and improves survival during acetaminophen toxicity. Glutamine may augment host defenses by enhancing antioxidant protection.

Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity.

Abstract: The use of amputation in extremity soft tissue sarcoma has been decreasing at Memorial Sloan-Kettering Cancer Center (MSKCC) over the last 15 years. In an attempt to define the efficacy and future role of amputation in extremity soft tissue sarcoma, a prospective sarcoma database compiled at MSKCC from July 1982 to January 1990, consisting of 649 patients, was analyzed in a retrospective fashion. Ninety-two patients underwent amputation, and 557 had a limb-sparing procedure. Patients selected for amputation were those who had large (T greater than or equal to 5 cm) high-grade tumors that invaded major vascular or nervous structures. The amputation group achieved significantly better local control than the limb-sparing group (p = 0.007). No survival benefit could be demonstrated, however, in the groups selected for amputation (i.e., large, high-grade tumors) when compared with patients undergoing a limb-sparing procedure with similar tumors. Prevention of local recurrence by amputation also did not improve survival in this group compared with similar patients undergoing limb-sparing surgery who did develop a local recurrence. The group of patients with high-grade tumors 10 cm or larger who received chemotherapy did have a significant improvement in survival (p = 0.01) compared with a similar group of patients who did not receive chemotherapy, regardless of the type of operation. The prognosis of patients most likely to undergo an amputation for extremity soft tissue sarcoma (those with high-grade, large tumors) is not related to their local disease, but rather to the risk of distant metastases. Therefore, amputation in this cohort of patients can be recommended only when a limb-sparing procedure cannot achieve gross resection of tumor while still preserving a useful extremity, because amputation improves only local control and does not address distant disease. Further improvement in survival in this group of patients will be dependent on better systemic treatment for extremity soft tissue sarcoma, and not on more radical surgery.

Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein.

Abstract: This retrospective study attempted to determine the indications for extended pancreatectomy for locally advanced carcinoma of the pancreas, in terms of postoperative prognosis. An extended pancreatectomy with portal vein or superior mesenteric vein (PV/SMV) resection and regional lymphadenectomy was performed in 35 of 50 consecutive cancers that extended into the retroperitoneal spaces and involved the PV or SMV. Among the many background factors in the 35 resected specimens, the degree of PV/SMV invasion by the cancer was most closely associated with prognosis, despite resection of all involved PV/SMV. This factor generally correlated with the preoperative findings on the portal phase of superior mesenteric arteriograph. In 17 selected patients in whom PV/SMV invasion had been angiographically both semicircular or less and 1.2 cm (1.4 cm on the film) or less in length, the 3-year survival rate was 59%. This survival rate was significantly higher than the 29% 3-year survival rate in all 35 patients (p less than 0.05). Conversely, among the 18 patients in whom invasion was angiographically either beyond semicircular or more than 1.2 cm (1.4 cm on the film) in length, there were no 1.5-year survivors, and this result was even worse than that of 15 nonresectable cases. Based on postoperative survival, the degrees of PV/SMV invasion on preoperative angiography (narrowing pattern and length) are good indicators for aggressive pancreatectomy for locally advanced pancreatic cancer.

Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management, and outcome.

Abstract: Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects.

Abstract: Serous cystadenoma of the pancreas is a rare lesion thought to be almost invariably benign. Since 1978, 211 cases have been reported in the literature. Some have been recognized by computed tomography (CT) when small and asymptomatic. The authors have reviewed their experience with 40 patients (median follow-up of 1.9 years, maximum of 22.2 years) from 1936 to 1991. One third (13) were asymptomatic, of whom eight (20%) were discovered intraoperatively. Of those 20 who had CT, an unequivocal preoperative diagnosis was reached in none. Needle biopsy proved accurate in two patients. Endoscopic retrograde cholangiopancreatography (ERCP) and biopsy were performed with diagnostic success on one occasion. Three patients presented acutely. The tumor was resected in 90%, with an operative mortality rate of 10%. Enucleation of the tumor without formal anatomic pancreatectomy necessitated reoperation for complications in four of eight patients. Survival after successful resection paralleled expected survival. Serous cystadenoma may be associated with von Hippel-Lindau syndrome. The current role for conservative management remains questionable because of our current inability to reliably differentiate many of these benign neoplasms from malignant cystic neoplasms of the pancreas.

Significant trends in the treatment of hepatic trauma. Experience with 411 injuries.

Abstract: Several significant advances in the treatment of hepatic injuries have evolved over the past decade. These trends have been incorporated into the overall treatment strategy of hepatic injuries and are reflected in experiences with 411 consecutive patients. Two hundred fifty-eight patients (63%) with minor injuries (grades I to II) were treated by simple suture or hemostatic agents with a mortality rate of 6%. One hundred twenty-eight patients (31%) sustained complex hepatic injuries (grades III to V). One hundred seven patients (83.5%) with grades III or IV injury underwent portal triad occlusion and finger fracture of hepatic parenchyma alone. Seventy-three surviving patients (73%) required portal triad occlusion, with ischemia times varying from 10 to 75 minutes (mean, 30 minutes). The mortality rate in this group was 6.5% (seven patients) and was accompanied by a morbidity rate of 15%. Fourteen patients (11%) with grade V injury (retrohepatic cava or hepatic veins) were managed by prolonged protal triad occlusion (mean cross-clamp time, 46 minutes) and extensive finger fracture to the site of injury. In four of these patients an atrial caval shunt was additionally used. Two of these patients survived, whereas six of the 10 patients managed without a shunt survived, for an overall mortality rate of 43%. Over the past 4 years, six patients (4.7%) with ongoing coagulopathies were managed by packing and planned re-exploration, with four patients (67%) surviving and one (25%) developing an intra-abdominal abscess. One additional patient (0.8%) was managed by resectional debridement alone and survived. During the past 5 years, 25 hemodynamically stable and alert adult patients (6%) sustaining blunt trauma were evaluated by computed tomography scan and found to have grade I to III injuries. All were managed nonoperatively with uniform success. The combination of portal triad occlusion (up to 75 minutes), finger fracture technique, and the use of a viable omental pack is a safe, reliable, and effective method of managing complex hepatic injuries (grade III to IV). Juxtahepatic venous injuries continue to carry a prohibitive mortality rate, but nonshunting approaches seem to result in the lowest cumulative mortality rate. Packing and planned reexploration has a definitive life-saving role when used adjunctively in the presence of a coagulopathy. Nonoperative management of select hemodynamically stable adult patients, identified by serial computed tomography scans after sustaining blunt trauma is highly successful (95-97%).

Curative resection in Zollinger-Ellison syndrome. Results of a 10-year prospective study.

Abstract: Since 1980, 73 patients with Zollinger-Ellison syndrome (ZES) without radiographic evidence of liver metastases were studied on a prospective protocol including medical management of gastric acid hypersecretion, extensive radiographic tumor localization, and exploratory surgery to find and resect gastrinoma for potential cure. Each patient had gastric acid hypersecretion effectively controlled with either H2-blockers or omeprazole. Patients were divided prospectively into two groups, with all patients undergoing the same preoperative localization studies and extensive laparotomy. In contrast to group 1 (1980-1986) (36 patients), group 2 (1987-Oct. 1990) (37 patients) also underwent additional procedures (transillumination and duodenotomy) at surgery to find duodenal gastrinomas. Preoperative imaging studies localized tumor in 38 (52%) patients, and portal venous sampling for gastrin determinations was positive in 49 (67%) patients. Gastrinomas were found and resected in 57 (78%) patients. Significantly more gastrinomas (92% of patients) were found in group 2 than in group 1 patients (64%) (p less than 0.01). This increase was due to increased numbers of duodenal gastrinomas in group 2 than in group 1 patients (43% versus 11%; p less than 0.01). The increased ability to find duodenal gastrinomas did not significantly improve the immediate disease-free rate, which was 58% for all patients. Duodenal primary gastrinomas were found to have a significantly greater incidence of metastases (55%) and a significantly shorter disease-free interval (12 months) than pancreatic gastrinomas (22% and 84 months, respectively) suggesting that duodenal gastrinomas may be more malignant and not more frequently curable than pancreatic gastrinomas. Operations were performed with no deaths and 11% morbidity rate. Long-term follow-up showed that 50% of patients initially rendered disease free would develop recurrent disease by 5 years. Survival was excellent for all patients, and none died of malignant spread of the tumor or uncontrolled peptic ulcer disease, with a mean follow-up of 5 years. This finding is in contrast to patients who presented with metastatic disease on imaging studies and had a 20% 5-year survival rate. This study suggests that all patients with localized sporadic ZES can have the gastric acid hypersecretion managed medically, that overall survival of these patients is excellent, most (78%) can have all gastrinoma found and resected, and some (30%) will be cured (long-term disease-free survival).

Abdominal packing for surgically uncontrollable hemorrhage.

Abstract: Planned intra-abdominal packing for surgically uncontrollable hemorrhage from liver and retroperitoneal injuries exacerbated by hypothermia, acidosis, and coagulopathy regained popularity over the past decade. The authors reviewed 39 patients injured between August 1985 and September 1990; 31 packed for liver injuries, eight for nonliver injuries. The overall mortality rate was 44% (17/39); 9 (23%) exsanguinated, 3 (8%) died of head injuries, 3 (8%) of multisystem organ failure, 2 (5%) of late complications. The mean age was 33.9 +/- 16.2 (range, 16 to 79); there were 26 men and 13 women. Relaparotomy for pack removal was performed 2.0 +/- 1.1 days (range, 1 to 7) after initial operation. The authors identified intraoperative risk factors of pH less than or equal to 7.18, temperature less than or equal to 33 C, prothrombin time greater than or equal to 16, partial thromboplastin time greater than or equal to 50, and transfusion of 10 units or more of blood as highly predictive of outcome. Patients with four to five risk factors (n = 3) had a 100% mortality rate (p less than 0.04); two to three risk factors (n = 12), 83% mortality rate (p less than 0.003), compared with zero to one risk factors (n = 24), 18% mortality rate. Complications developed in six of 22 survivors (27%): 5 abdominal abscesses (23%), 2 wound dehiscences (9%), and 2 enterocutaneous fistulae (9%). Intra-abdominal packing will not stop all bleeding; 23% of the patients exsanguinated. In 77%, packing helped achieve hemostasis we believed was not otherwise possible. Packing may be done to prevent the development of acidosis, hypothermia, and coagulopathy or may be done early in the treatment of cold, acidotic patients rather than massive transfusion in the face of surgically uncorrectable bleeding.

Intestinal transplantation in composite visceral grafts or alone.

Abstract: Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.

Laparoscopic injuries to the bile duct. A cause for concern.

Abstract: The authors report six patients who had injuries to their common hepatic bile duct at laparoscopic cholecystectomy over a 16-month period. Five of the six complications could be attributed to laser injuries during dissection in the region of Calot's triangle. The authors discuss the possible mechanism of these injuries, their perioperative management, and the methods of surgical reconstruction. The follow-up period ranges from 3 months to 21 months. Liver function parameters and isotope biliary excretion scans are back to normal in all six patients. The potential hazards of laparoscopic surgery demand that extraordinary care be used not only during the actual surgical procedure, but also in the preoperative decision concerning the dissection method to be employed.

Infected aortic aneurysms. A changing entity.

Abstract: Infected (mycotic) aortic aneurysms are infrequent and, without surgical intervention, usually lead to uncontrolled sepsis or catastrophic hemorrhage. Symptoms are frequently absent or non-specific during the early stages, and a high index of suspicion is essential to make the diagnosis. Surgery performed after rupture carries high morbidity and mortality rates. Bacterial endocarditis with streptococcus pyogenes was the most common cause of infected aortic aneurysm in the pre-antibiotic era. Today, arterial trauma due to iatrogenic manipulation and depressed immunocompetence have become more common risk factors. Staphylococcus aureus and Salmonella are the most frequent bacteria identified. The authors' recent experience in six patients with infected aortic aneurysms who underwent arteriography and computed tomography was reviewed and these diagnostic methods compared. Computed tomography was found to be more sensitive in the diagnosis of the early stages of the disease, allowing for follow-up by serial scans in a noninvasive and less costly manner. Successful treatment, in four of these patients, was accomplished by aneurysmal resection and extra-anatomic bypass or in situ prosthetic reconstruction. A higher clinical awareness of this disease, leading to early computed tomography evaluation and prompt surgical intervention under appropriate and intensive antibiotic therapy, appears to offer the best chance of survival in patients with this difficult condition.

The application of positron emission tomographic imaging with fluorodeoxyglucose to the evaluation of breast disease.

Abstract: Positron emission tomography (PET) is a computer-aided tomographic imaging technique that uses positron-emitting compounds to trace biochemical processes of tissue, and construct images based on them. The authors applied a whole-body PET imaging technique to patients with breast masses or mammographic abnormalities using the isotope 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), in a clinical trial to evaluate the feasibility of using PET to identify primary breast cancer, axillary lymph node involvement, and systemic metastases, before surgical resection. Fourteen patients have been entered on this study, 10 of whom proved to have breast cancer. Positron emission tomography correctly predicted the nature of 12 of the 14 primary breast lesions, and correctly determined the lymph node status of 11 of the 14 patients. The authors conclude that PET with FDG has potential as a diagnostic modality for detection of primary breast cancer, particularly in the patient with radiodense breasts by conventional mammography, and that it has potential for the preoperative identification of axillary lymph node metastases.