Showing papers in "Annals of Surgery in 1995"

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.

Abstract: OBJECTIVE: This report documents that the gastric bypass operation provides long-term control for obesity and diabetes. SUMMARY BACKGROUND DATA: Obesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. METHODS: Over the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (< 3%) were lost to follow-up. RESULTS: Gastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 to 615 lb) to 192.2 lb (range, 104 to 466) by 1 year and were maintained at 205.4 lb (range, 107 to 512 lb) at 5 years, 206.5 lb (130 to 388 lb) at 10 years, and 204.7 lb (158 to 270 lb) at 14 years. The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. Gastric bypass is now established as an effective and safe therapy for morbid obesity and its associated morbidities. No other therapy has produced such durable and complete control of diabetes mellitus.

Ileal pouch-anal anastomoses complications and function in 1005 patients

Abstract: BackgroundRestorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) has become an established surgery for patients with chronic ulcerative colitis and familial adenomatous polyposis.PurposeThe authors report the results of an 11-year experience of restorative proctocolectomy and IPAA at a

Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients

Abstract: OBJECTIVE: This single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. METHODS: Two hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. RESULTS: The overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections; n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, < 800 mL intraoperative blood loss, < 2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection. CONCLUSIONS: The survival of patients with pancreatic adenocarcinoma treated by pancreaticoduodenectomy is improving. Aspects of tumor biology, such as DNA content, tumor diameter, nodal status and margin status, are the strongest predictors of outcome.

Improved axillary staging of breast cancer with sentinel lymphadenectomy.

Abstract: Objective The authors evaluated the effect of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) on the axillary staging of patients with carcinoma of the breast. Background Data The accurate staging of patients with breast cancer is essential to guide management and determine prognosis. The authors previously reported the feasibility and accuracy of SLND in breast carcinoma. Sentinel lymphadenectomy identifies the first (sentinel) axillary lymph node draining the site of a primary tumor ; because this node is the most likely site of axillary metastasis, histopathologic examination of the sentinel node correlates well with examination of the entire axillary contents. The current study compares SLND with standard axillary lymphadenectomy (ALND) for the staging of breast carcinoma. Methods The incidence of axillary node metastasis and micrometastasis in SLND and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared prospectively. Multiple sections of each sentinel lymph node in SLND specimens were examined by hematoxylin and eosin (H&E) staining and by immunohistochemical techniques using antibodies to cytokeratin. One or two sections of each nonsentinel lymph node in ALND specimens were examined by routine H&E staining. Results One hundred thirty-four patients underwent ALND (ALND group), and 162 underwent successful SLND followed by completion ALND (SLND group). Both groups were similar with respect to age (median, 55 and 54 years, respectively), palpable primary tumors (54.5% and 59.3%, respectively), palpable axillary nodes (5.2% and 7.4%, respectively), size of primary tumor (median, 1.5 cm in each group), and total number of axillary lymph nodes examined (median, 19 and 21, respectively). The number of patients with axillary metastasis was 39 (29.1%) in the ALND group and 68 (42.0%) in the SLND group (p < 0.03). Of these, 4 of 39 (10.3%) ALND patients (3.0% of all ALND patients) and 26 of 68 (38.2%) SLND patients (16.0% of all SLND patients) had micrometastasis (≤2 mm), a highly significant difference (p < 0.0005) Conclusions Sentinel lymphadenectomy with multiple sectioning and immunohistochemical staining of sentinel nodes increases the accuracy of axillary staging in breast cancer and can identify significantly more patients with lymph nodes metastases, especially micrometastases, than can ALND with routine histopathologic processing of lymph nodes.

Determinants of mortality for necrotizing soft-tissue infections.

Abstract: OBJECTIVE: The authors determined the risk factors of mortality in patients with necrotizing soft-tissue infections (NSTIs) and examined the incidence and mortality from NSTI secondary to Streptococcus pyogenes. METHODS: All patients with NSTIs who were treated between January 1989 and June 1994 were analyzed for presentation, etiology, factors important in pathogenesis and treatment, and mortality. RESULTS: Sixty-five patients were identified with NSTIs secondary to postoperative wound complications (18), trauma (15), cutaneous disease (15), idiopathic causes (10), perirectal abscesses (3), strangulated hernias (2), and subcutaneous injections (2). Necrotizing soft-tissue infections were polymicrobial in 45 patients (69%). S. pyogenes was isolated in only 17% of the NSTIs, but accounted for 53% of monomicrobial infections. Eight of ten idiopathic infections were caused by a single bacterium (p = 0.0005), whereas 82% of postoperative infections were polymicrobial. An average of 3.3 operative debridements per patient and amputation in 12 patients were necessary to control infection. The overall mortality was 29%; mortality from S. pyogenes infection was only 18%. The average time from admission to operation was 90 hours in nonsurvivors versus 25 hours in survivors (p = 0.0002). Other risk factors previously associated with the development of NSTIs did not affect mortality. CONCLUSIONS: Early debridement of NSTI was associated with a significant decrease in mortality. S. pyogenes infection was the most common cause of monomicrobial NSTI, but was not associated with an increased mortality.

A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy

Abstract: Objective The authors hypothesized that pancreaticogastrostomy is safer than pancreaticojejunostomy after pancreaticoduodenectomy and less likely to be associated with a postoperative pancreatic fistula. Summary Background Data Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy, occurring in 10% to 20% of patients. Nonrandomized reports have suggested that pancreaticogastrostomy is less likely than pancreaticojejunostomy to be associated with postoperative complications. Methods Between May 1993 and January 1995, the findings for 145 patients were analyzed in this prospective trial at The Johns Hopkins Hospital. After giving their appropriate preoperative informed consent, patients were randomly assigned to pancreaticogastrostomy or pancreaticojejunostomy after completion of the pancreaticoduodenal resection. All pancreatic anastomoses were performed in two layers without pancreatic duct stents and with closed suction drainage. Pancreatic fistula was defined as drainage of greater than 50 mL of amylase-rich fluid on or after postoperative day 10. Results The pancreaticogastrostomy (n = 73) and pancreaticojejunostomy (n = 72) groups were comparable with regard to multiple parameters, including demographics, medical history, preoperative laboratory values, and intraoperative factors, such as operative time, blood transfusions, pancreatic texture, length of pancreatic remnant mobilized, and pancreatic duct diameter. The overall incidence of pancreatic fistula after pancreaticoduodenectomy was 11.7% (17/145). The incidence of pancreatic fistula was similar for the pancreaticogastrostomy (12.3%) and pancreaticojejunostomy (11.1%) groups. Pancreatic fistula was associated with a significant prolongation of postoperative hospital stay (36 ± 5 vs. 15 ± 1 days) (p < 0.001). Factors significantly increasing the risk of pancreatic fistula by univariate logistic regression analysis included ampullary or duodenal disease, soft pancreatic texture, longer operative time, greater intraoperative red blood cell transfusions, and lower surgical volume (p < 0.05). A multivariate logistic regression analysis revealed the factors most highly associated with pancreatic fistula to be lower surgical volume and ampullary or duodenal disease in the resected specimen. Conclusions Pancreatic fistula is a common complication after pancreaticoduodenectomy, with an incidence most strongly associated with surgical volume and underlying disease. These data do not support the hypothesis that pancreaticogastrostomy is safer than pancreaticojejunostomy or is associated with a lower incidence of pancreatic fistula.

Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?

Abstract: OBJECTIVE: The authors review their recent experience with resected pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the pancreas has traditionally had a 5-year survival rate less than 10% after curative resection. Recently, several groups have reported markedly improved 5-year survival rates (approaching 25%) for patients undergoing curative resection. METHODS: Institutional experience with 186 consecutive patients (1981-1991) with pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed by two pathologists, one internal and one external; nonductal pancreatic cancers then were excluded. RESULTS: After histologic re-review, 12 patients did not have ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72 women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range 4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus-preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98 (56%) had lymph node metastases within the resected specimens, and 21 patients (12%) had extensive perineural invasion. Overall actuarial 5-year survival was 6.8%. Five-year survival was greater for node-negative versus node-positive patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p < 0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer. CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.

Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy.

Abstract: OBJECTIVE: A treatment plan to be used in patients with peritoneal carcinomatosis was devised and tested as a Phase II study. BACKGROUND: Peritoneal carcinomatosis from appendical or colorectal cancer has been regarded as a fatal clinical entity. Treatment protocols have not been reported previously. METHODS: The authors used cytoreductive surgery and intraperitoneal chemotherapy to treat 181 consecutive patients with peritoneal carcinomatosis. There were 51 patients with colorectal cancer and 130 patients with appendiceal cancer. Mean follow-up is 24 months, with a range of 0 to 149 months. RESULTS: Clinical features that showed prognostic significance included appendiceal versus colorectal primary tumors (p = 0.0001), grade 1 versus grades 2 and 3 histopathology (p = 0.0003), complete versus incomplete cytoreductions (p = 0.0001), lymph node-negative versus lymph node-positive primary tumors (p = 0.0001), and volume of peritoneal carcinomatosis present preoperatively for colon cancer (p = 0.0006). Features with no statistical prognostic significance included preoperative tumor volume for appendiceal cancer, age, sex, number of cycles of chemotherapy, operative time, complications, blood loss, and institution providing treatment. From these prognostic features, four prognostic groups were identified, and 3-year survival was estimated by the product-limit survival method. Group I patients (n = 76) were those with grade 1 histology, no lymph node metastases, and complete cytoreductions (survival at 3 years = 99%). Group II patients (n = 23) were those with grade 2 or 3 histology, no lymph node metastases, and complete cytoreductions (65%). Group III patients (n = 24) had any histology, lymph node metastases, and complete cytoreductions (66%). Group IV patients (n = 58) had incomplete cytoreductions (20%).

A meta-analysis of selective versus routine nasogastric decompression after elective laparotomy

Abstract: OBJECTIVE: A meta-analysis of all published clinical trials comparing selective versus routine nasogastric decompression was performed in an attempt to evaluate the need for nasogastric decompression after elective laparotomy. BACKGROUND: Many studies have suggested that routine nasogastric decompression is unnecessary after elective laparotomy and may be associated with an increased incidence of complications. Despite these reports, many surgeons continue to practice routine nasogastric decompression, believing that its use significantly decreases the risk of postoperative nausea, vomiting, aspiration, wound dehiscence, and anastomotic leak. METHODS: A comprehensive search of the English language medical literature was performed to identify all published clinical trials evaluating nasogastric decompression. Twenty-six trials (3964 patients) met inclusion criteria. The outcome data extracted from each trial were subsequently "pooled" and analyzed for significant differences using the Mantel-Haenszel estimation of combined relative risk. RESULTS: Fever, atelectasis, and pneumonia were significantly less common and days to first oral intake were significantly fewer in patients managed without nasogastric tubes. Meta-analysis based on study quality revealed significantly fewer pulmonary complications, but significantly greater abdominal distension and vomiting in patients managed without nasogastric tubes. Routine nasogastric decompression did not decrease the incidence of any other complication. CONCLUSIONS: Although patients may develop abdominal distension or vomiting without a nasogastric tube, this is not associated with an increase in complications or length of stay. For every patient requiring insertion of a nasogastric tube in the postoperative period, at least 20 patients will not require nasogastric decompression. Routine nasogastric decompression is not supported by meta-analysis of the literature.

Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection.

Abstract: Objective Patients with serious traumatic injury and major burns and an animal model of burn injury were studied to determine the effect of injury on the production of cytokines typical of the T helper-2 lymphocyte phenotype as opposed to the T helper-1 phenotype and on the production of interleukin-12. Summary Background Data Perturbations of natural and adoptive immunity are related to the increased susceptibility to infection manifested by seriously injured and burn patients. Earlier work has shown that impaired adoptive immunity after injury is characterized by diminished production of interleukin-2 (IL-2), a product of Th lymphocytes. Exposure of naive Th cells to certain antigens and cytokines causes conversion to either the Th-1 or the Th-2 phenotype. Th-1 cells produce IL-2 and interferon-gamma (IFN-τ) and initiate cellular immunity. Th-2 cells secrete interleukin-4 (IL-4) and interleukin-10 (IL-10) and stimulate production of certain antibodies. Conversion to the Th-1 phenotype is facilitated by IL-12, and conversion to the Th-2 phenotype is promoted by IL-4. The authors believed that serious injury might cause conversion of Th cells to the Th-2 as opposed to the Th-1 phenotype rather than generalized Th suppression. Methods The authors studied circulating peripheral blood mononuclear cells (PBMC) from 16 major burn and 8 trauma patients on 32 occasions early after injury and from 13 age- and sex-matched healthy individuals for cytokine production after phytohemagglutinin stimulation. Also studied was a mouse model of 20% burn injury known to mimic the immune abnormalities seen in humans with burns. Splenocytes from burn mice, 10 to 12 per group, were studied after activation by concanavalin A or by the bacterial antigen Staphylococcus aureus Cowan strain I for cytokine production and cytokine messenger RNA expression as determined by reverse transcriptase polymerase chain reaction. Burn mice were compared with sham-burn controls and attention was focused on day 10 after burn injury, a time when IL-2 production and resistance to infection are highly suppressed. Finally, burn and sham-burn animals, 20 per group, were treated in vivo with IL-12 (25 ng daily for 5 days) and observed for mortality after septic challenge (cecal ligation and puncture [CLP]) performed on day 10 after injury. Results Peripheral blood mononuclear cells from burn and trauma patients produced less IFN-τ, the index cytokine of Th-1 cells, than PBMCs from healthy individuals 1 to 14 days after burn injury (SE = 77.6 ± 16 pg/mL patients vs. 141.3 ± 35 pg/mL controls, p < 0.05). However, production of IL-4, the index cytokine of Th-2 cells, by patient PBMCs was increased (51.0 ± 13.0 pg/mL patients vs. 26.9 ± 2.5 controls, p < 0.05). Splenocytes from mice 10 days after burn injury, when compared with sham-burn controls, showed diminished production of IL-2 (1.04 ± 0.91 units/mL burns vs. 5.8 ± 0.55 units/mL controls, p < 0.05) and IFN-τ (1.05 ± 0.7 units/mL burns vs. 12.0 ± 8.9 units/mL controls, p < 0.05). However, burn splenocytes produced more IL-4 (2492 ± 157.0 pg/mL burns vs. 672.0 ± 22.7 pg/mL controls, p < 0.01) and IL-10 (695.2 ± 20.8 pg/mL burns vs. 567.0 ± 16.7 pg/mL controls, p < 0.05). Splenocyte production of IL-12 was also reduced after burn (0.20 ± 0.035 units/mL) as compared with sham burn (0.46 ± 0.08 units/mL, p < 0.05). The reduction in IL-2, IFN-τ, and IL-12 production by burn splenocytes was reflected by a tenfold decrease in expression of their respective cytokine mRNAs.

The Effects of Regionalization on Cost and Outcome for One General High-Risk Surgical Procedure

Abstract: PurposeThe effects of regionalization of tertiary care were studied by analyzing cost and outcome for pancreaticoduodenectomies in a state in which the majority of these high-risk procedures were performed in one hospital.MethodsUsing Maryland inpatient discharge data via a retrospective study, the

Nonoperative management of blunt hepatic trauma is the treatment of choice for hemodynamically stable patients. Results of a prospective trial.

Abstract: BACKGROUND: A number of retrospective studies recently have been published concerning nonoperative management of minor liver injuries, with cumulative success rates greater than 95%. However, no prospective analysis that involves a large number of higher grade injuries has been reported. The current study was conducted to evaluate the safety of nonoperative management of blunt hepatic trauma in hemodynamically stable patients regardless of injury severity. METHODS: Over a 22-month period, patients with blunt hepatic injury were evaluated prospectively. Unstable patients underwent laparotomies, and stable patients had abdominal computed tomography (CT) scans. Those with nonhepatic operative indications underwent exploration, and the remainder were managed nonoperatively in the trauma intensive care unit. This group was compared with a hemodynamically matched operated cohort of blunt hepatic trauma patients (control subjects) who had been prospectively analyzed. RESULTS: One hundred thirty-six patients had blunt hepatic trauma. Twenty-four (18%) underwent emergent exploration. Of the remaining 112 patients, 12 (11%) failed observation and underwent celiotomy--5 were liver-related failures (5%) and 7 were nonliver related (6%). Liver related failure rates for CT grades I through V were 20%, 3%, 3%, 0%, and 12%, respectively, and rates according to hemoperitoneum were 2% for minimal, 6% for moderate, and 7% for large. The remaining 100 patients were successfully treated without operation--30% had minor injuries (grades I-II) and 70% had major (grades III-V) injuries. There were no differences in admission characteristics between nonoperative success or failures, except admission systolic blood pressure (127 vs. 104; p < 0.04). Comparing the nonoperative group to the control group, there were no differences in admission hemodynamics or hospital length of stay, but nonoperative patients had significantly fewer blood transfusions (1.9 vs. 4.0 units; p < 0.02) and fewer abdominal complications (3% vs. 11%; p < 0.04). CONCLUSIONS: Nonoperative management is safe for hemodynamically stable patients with blunt hepatic injury, regardless of injury severity. There are fewer abdominal complications and less transfusions when compared with a matched cohort of operated patients. Based on admission characteristics or CT scan, it is not possible to predict failures; therefore, intensive care unit monitoring is necessary.

Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis.

Abstract: OBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. METHODS: Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. RESULTS: Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria. CONCLUSION: Reduction of gram-negative colonization of the digestive tract, preventing subsequent pancreatic infection by means of selective decontamination, significantly reduces morbidity and mortality in patients with severe acute necrotizing pancreatitis.

Hepatic resection for hepatocellular carcinoma. An audit of 343 patients.

Abstract: ObjectiveThe authors summarize the results of patients who had hepatectomy for hepatocellular carcinoma over a 22-year period.Summary Background DataRecent reports showed improved perioperative results and long-term prognosis.MethodsThe perioperative outcome of 343 patients was studied according to

A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine, and a modified diet

Abstract: OBJECTIVE: The purpose of this study was to initially determine if growth hormone or nutrients, given alone or together, could enhance absorption from the remnant small bowel after massive intestinal resection. If clinical improvement were observed, this therapy would then be used to treat patients with the short-bowel syndrome over the long term. SUMMARY BACKGROUND DATA: Patients who undergo extensive resection of the gastrointestinal tract frequently develop malabsorption and require long-term parenteral nutrition. The authors hypothesized that the administration of growth factors and/or nutrients could enhance further compensation of the remnant intestine and thereby improve absorption. Specifically, animal studies have shown that there is enhanced cellularity with the administration of growth hormone (GH) or glutamine (GLN), or a fiber-containing diet. METHODS: Initially, 17 studies were performed in 15 total parenteral nutrition (TPN)-dependent short-bowel patients over 3 to 4 weeks in the clinical research center; the first week served as a control period, and during the next 1 to 3 weeks, the specific treatment was administered and evaluated. Throughout the study, food of known composition was provided and all stool was collected and analyzed to determine absorption across the remaining bowel. The effect of a high-carbohydrate, low-fat diet (DIET), the amino acid glutamine (GLN) and growth hormone (GH) administered alone or in combination with the other therapies (GH + GLN + DIET) was evaluated. The treatment was expanded to 47 adults (25 men, 22 women) with the short-bowel syndrome, dependent on TPN for 6 +/- 1 years. The average age was 46 +/- 2 years, and the average jejunal-ileal length was 50 +/- 7 cm (median 35 cm) in those with all or a portion of colon and 102 +/- 24 cm (median 102 cm) in those with no colon. After 28 days of therapy, the patients were discharged on only GLN + DIET. RESULTS: The initial balance studies indicated improvement in absorption of protein by 39% accompanied by a 33% decrease in stool output with the GH + GLN + DIET. In the long-term study, 40% of the group remain off TPN and an additional 40% have reduced their TPN requirements, with follow-up averaging a year and the longest being over 5 years. CONCLUSION: GH + GLN + DIET offers a potential method for providing cost-effective rehabilitation of surgical patients who have the short-bowel syndrome or other complex problems of the gastrointestinal tract. This therapeutic combination also may be useful to enhance bowel function in patients with other gastrointestinal diseases and those requiring extensive intestinal operations, including transplantation.

Is early oral feeding safe after elective colorectal surgery? A prospective randomized trial.

Abstract: IntroductionThe routine use of a nasogastric tube after elective colorectal surgery is no longer mandatory. More recently, early feeding after laparoscopic colectomy has been shown to be safe and well tolerated. Therefore, the aim of our study was to prospectively assess the safety and tolerability

Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized.

Abstract: OBJECTIVE: The author's goal was to determine the role of duodenal components in the development of complications of gastroesophageal reflux disease. SUMMARY AND BACKGROUND DATA: There is a disturbing increase in the prevalence of complications, specifically the development of Barrett's esophagus among patients with gastroesophageal reflux disease. Earlier studies using pH monitoring and aspiration techniques have shown that increased esophageal exposure to fluid with a pH above 7, that is, of potential duodenal origin, may be an important factor in this phenomenon. METHODS: The presence of duodenal content in the esophagus was studied in 53 patients with gastroesophageal reflux disease confirmed by 24-hour pH monitoring. A portable spectrophotometer (Bilitec 2000, Synectics, Inc.) with a fiberoptic probe was used to measure intraluminal bilirubin as a marker for duodenal juice in the esophagus. Normal values for bilirubin monitoring were established for 25 healthy subjects. In a subgroup of 22 patients, a custom-made program was used to correlate simultaneous pH and bilirubin absorbance readings. RESULTS: Fifty-eight percent of patients were found to have increased esophageal exposure to gastric and duodenal juices. The degree of mucosal damage increased when duodenal juice was refluxed into the esophagus, in that patients with Barrett's metaplasia (n = 27) had a significantly higher prevalence of abnormal esophageal bilirubin exposure than did those with erosive esophagitis (n = 10) or with no injury (n = 16). They also had a greater esophageal bilirubin exposure compared with patients without Barrett's changes, with or without esophagitis. The correlation of pH and bilirubin monitoring showed that the majority (87%) of esophageal bilirubin exposure occurred when the pH of the esophagus was between 4 and 7. CONCLUSIONS: Reflux of duodenal juice in gastroesophageal reflux disease is more common than pH studies alone would suggest. The combined reflux of gastric and duodenal juices causes severe esophageal mucosal damage. The vast majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids, the major component of duodenal juice, are capable of damaging the esophageal mucosa.

Laparoscopic inguinal herniorrhaphy. Results of a multicenter trial.

Abstract: OBJECTIVE: The purpose of this study was to determine if laparoscopic inguinal herniorrhaphy represents a viable alternative to the conventional repair and to assess whether a prospective randomized controlled trial comparing both procedures is warranted. METHODS: Three types of laparoscopic inguinal herniorrhaphies (transabdominal preperitoneal [TAPP], intraperitoneal onlay mesh [IPOM], and totally extraperitoneal [EXTRA]) were studied in a phase II design. Twenty-one investigators from 19 institutions participated. Approval from the local human research committee was required at each institution before patients could be enrolled. RESULTS: There were 686 patients with 869 hernias; 366 (42.1%) were direct, 414 (47.6%) were indirect, 22 (2.5%) were femoral, and 67 (7.7%) were combination hernias. The TAPP procedure was used for 562 hernias, the IPOM was used for 217 hernias, and the EXTRA was used for 87 hernias. Sixty-one patients had additional abdominal procedures performed at the time of laparoscopy without any adverse affects on their herniorrhaphies. The overall recurrence rate was 4.5%, with a minimum follow-up of 15 months. Complications were divided into the following three groups: 1) those related to laparoscopy, 2) those related to the patient, and 3) those related to the herniorrhaphy. Complications related to the laparoscopy occurred in 5.4% of patients; bleeding or abdominal wall hematomas occurred 31 times, (two patients required transfusion); one patient had bowel perforation, which was sutured laparoscopically; a bladder injury required laparotomy for management. Patient complications occurred in 6.7%. The majority involved the urinary tract (5.8%). Two patients required secondary abdominal procedures for adhesions, one for pain in the right lower quadrant and the other for adhesive small bowel obstruction. Postoperative myocardial infarction on day 5 resulted in the only operative mortality, for a rate of 0.1%. Complications related to the herniorrhaphy itself occurred in 17.1%. Most of these were minor, consisting of transient groin pain (3.5%), seroma (3.5%), transient leg pain (3.3%), hematoma (1.5%), or transient cord or testicular problems (0.9%). The incidence of leg pain decreased dramatically as surgeons became more familiar with the anatomy of the nerve supply to the groin when viewed laparoscopically. Ninety-three percent of patients were discharged within 24 hours of their operations. CONCLUSIONS: Laparoscopic inguinal herniorrhaphy is an effective method to correct an inguinal hernia. It can be offered safely to patients undergoing other abdominal procedures. The TAPP, IPOM, and EXTRA procedures appear to be equally effective. A controlled randomized trial is needed to compare this procedure with conventional inguinal herniorrhaphy.

Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients

Abstract: OBJECTIVE: The objective of this study was to evaluate long-term enteral nutrition support in postoperative cancer patients. BACKGROUND: Multimodality therapy for surgical patients with upper gastrointestinal malignancies may improve survival, but often results in substantial malnutrition, immunosuppression, and morbidity. The benefits of combined inpatient and outpatient enteral feeding with standard diets or diets supplemented with arginine, RNA + omega-3 fatty acids are unclear. METHODS: Sixty adult patients with esophageal (22), gastric (16), and pancreatic (22) lesions were stratified by disease site and percent usual weight and randomized to receive supplemental or standard diet via jejunostomy beginning on the first postoperative day (goal = 25 kcal/kg/day) until hospital discharge. Patients also were randomized to receive (n = 37) or not receive (n = 23) enteral jejunostomy feedings (1000 kcal/day overnight) for the 12- to 16-week recovery and radiation/chemotherapy periods. Plasma and peripheral white blood cells were obtained for fatty acid levels and PGE2 production measurements. RESULTS: Mean plasma and cellular omega 3/omega 6 fatty acid levels (percent composition) increased significantly (p < 0.05) in the arginine + omega-3 fatty acid group by postoperative day 7 (0.30 vs. 0.13) and (0.29 vs. 0.14) and continued to increase over time. Mean PGE2 production decreased significantly (p < 0.05) from 2760 to 1600 ng/10(6) cells/mL at day 7 in the arginine + omega-3 fatty acid group, whereas no significant change over time was noted in the standard group. Infectious/wound complications occurred in 10% of the supplemented group compared with 43% of the standard group (p < 0.05); mean length of hospital stay was 16 vs. 22 (p < 0.05) days, respectively. Of the patients who received postoperative chemoradiation therapy, only 1 (6%) of the 18 patients randomized to receive tube feeding did not continue, whereas 8 (61%) of the 13 patients not randomized to tube feedings required crossover to jejunostomy nutritional support. CONCLUSIONS: Supplemental enteral feeding significantly increased plasma and peripheral white blood cell omega 3/omega 6 ratios and significantly decreased PGE2 production and postoperative infectious/wound complications compared with standard enteral feeding. For outpatients receiving adjuvant therapy, those initially randomized to oral feedings alone required rehospitalization more frequently, and 61% crossed over to supplemental enteral feedings.

Improved Mortality and Rehabilitation of Transplant Candidates Treated with a Long-term Implantable Left Ventricular Assist System

Abstract: Objective This nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. Methods Outcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria : pulmonary capillary wedge pressure ≥ 20 mm Hg with a systolic blood pressure ≤ 80 mm Hg or a cardiac index ≤ 2.0 L/minute/m 2 . In addition, none of the patients met predetermined exclusion criteria. Results More LVAS patients than control patients survived to transplantation : 53 (71%) versus 12 (36%) (p = 0.001) ; and more LVAS patients were alive at 1 year : 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days ; range, <1-344 days) than in the control group (average, 12 days ; range, 1-72 days). In the LVAS group, the average pump index (2.77 L/minute/m 2 ) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m 2 ) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). Conclusions The LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS group, pretransplant mortality decreased by 55%, and the probability of surviving 1 year after transplant was significantly greater than in the control group (90% vs. 67%, p = 0.03). Thus, the HeartMate IP LVAS proved safe and effective as a bridge to transplant and decreased the risk of death for patients waiting for transplantation.

Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.

Abstract: OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra-abdominal metastases. Laparoscopic ultrasonography improves the accuracy of laparoscopic staging in patients with potentially resectable pancreatic and periampullary carcinomas.

Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized trial.

Abstract: OBJECTIVE: Two techniques of duodenum-preserving resection of the head of the pancreas were compared in a prospective, randomized trial. The technical feasibility and effects on quality of life were assessed. SUMMARY BACKGROUND DATA: Drainage and resection are the principles of surgery in chronic pancreatitis. The techniques of duodenum-preserving resection of the head of the pancreas as described by Berger and Frey combine both to different degrees. The efficacy of both procedures has not been compared thus far. METHODS: Forty-two patients were allocated randomly to either Beger's (n = 20) or Frey's (n = 22) group. In addition to routine pancreatic diagnostic work-up, a multidimensional psychometric quality-of-life questionnaire and and a pain score were used. Assessment of endocrine and exocrine function included oral glucose tolerance test, serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl test. The interval between symptoms and surgery ranged from 12 months to 12 years, with a mean of 5.7 years. The mean follow-up was 1.5 years. RESULTS: There was no mortality. Overall morbidity was 14% (20% Beger, 9% Frey). Complications from adjacent organs were resolved definitively in 94% (90% Beger, 100% Frey). A decrease of 95% and 94% of the pain score after Beger's and Frey's procedure, respectively, and an increase of 67% of the overall quality-of-life index in both groups were observed. Endocrine and exocrine function did not differ between both groups. CONCLUSIONS: Both techniques of duodenum-preserving resection of the head of the pancreas are equally safe and effective with regard to pain relief, improvement of quality of life, and definitive control of complications affecting adjacent organs. Neither procedure leads to further deterioration of endocrine and exocrine pancreatic function.

The Objective Structured Clinical Examination. The new gold standard for evaluating postgraduate clinical performance.

Abstract: ObjectiveThe authors determine the reliability, validity, and usefulness of the Objective Structured Clinical Examination (OSCE) in the evaluation of surgical residents.Summary Background DataInterest is increasing in using the OSCE as a measurement of clinical competence and as a certification tool

The natural history of appendicitis in adults. A prospective study.

Abstract: ObjectiveThe authors relate prehospital delay and in hospital delay to the incidence of perforation of appendicitis.Summary Background DataQuality assurance studies use perforation rate as an index of quality of care. This is based on the assumption commonly presented in retrospective reports that i

Initial experience with transluminally placed endovascular grafts for the treatment of complex vascular lesions.

Abstract: Objectives Complex arterial occlusive, traumatic, and aneurysmal lesions may be difficult or impossible to treat successfully by standard surgical techniques when severe medical or surgical comorbidities exist. The authors describe a single center's experience over a 2 1/2-year period with 96 endovascular graft procedures performed to treat 100 arterial lesions in 92 patients. Patients and Methods Thirty-three patients had 36 large aortic and/or peripheral artery aneurysms, 48 had 53 multilevel limb-threatening aortoiliac and/or femoropopliteal occlusive lesions, and 11 had traumatic arterial injuries (false aneurysms and arteriovenous fistulas). Endovascular grafts were placed through remote arteriotomies under local (16 [17%]), epidural (42 [43%]), or general (38 [40%]) anesthesia. Results Technical and clinical successes were achieved in 91% of the patients with aneurysms, 91% with occlusive lesions, and 100% with traumatic arterial lesions. These patients and grafts have been followed from 1 to 30 months (mean, 13 months). The primary and secondary patency rates at 18 months for aortoiliac occlusions were 77% and 95%, respectively. The 18-month limb salvage rate was 98%. Immediately after aortic aneurysm exclusion, a total of 6 (33%) perigraft channels were detected ; 3 of these closed within 8 weeks. Endovascular stented graft procedures were associated with a 10% major and a 14% minor complication rate. The overall 30-day mortality rate for this entire series was 6%. Conclusions This initial experience with endovascular graft repair of complex arterial lesions justifies further use and careful evaluation of this technique for major arterial reconstruction.

Perihilar cholangiocarcinoma: Postoperative radiotherapy does not improve survival

Abstract: Objective The aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma. Background Retrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma. However, in these reports, patients receiving radiotherapy tended to have smaller, often resectable tumors, and were relatively fit. In comparison, patients who have not received radiotherapy often had unresectable tumors, metastatic disease, or poor performance status. Methods From 1988 through 1993, surgically staged patients with perihilar cholangiocarcinoma and 1) no evidence of metastatic disease, 2) Karnofsky score >60, 3) no prior malignancy or radiotherapy, and 4) a patent main portal vein were analyzed. Fifty patients were stratified by resection (n = 31) versus operative palliation (n = 19) and by radiation (n = 23) versus no radiotherapy (n = 27). Results Patients undergoing resection had smaller tumors (1.9 ± 2.8 vs. 2.4 ± 2.1 cm, p < 0.01) that were less likely to invade the hepatic artery (3% vs. 42%, p < 0.05) or portal vein (6% vs. 53%, p < 0.05). Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy. Resection improved the length (24.2 ± 2.5 vs. 11.3 ± 1.0 months, p < 0.05) and quality of survival. Radiation had no effect on the length (18.4 ± 2.9 vs. 20.1 ± 2.4 months) or quality of survival or on late toxicity. Conclusions This analysis suggests that in patients with localized perihilar cholangiocarcinoma, resection prolongs survival whereas radiation has no effect on either survival or late toxicity. Thus, new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients.

Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The Paul Brousse experience.

Abstract: OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality.

Outcome analysis of 71 clinical intestinal transplantations

Abstract: Objective The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. Background Data Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. Methods Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. Results Of the first 63 recipients, 32 are alive : 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft-versus-host disease. Conclusion To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.

Pancreatic or liver resection for malignancy is safe and effective for the elderly.

Abstract: BACKGROUND: Liver resection, or pancreaticoduodenectomy, has traditionally been thought to have a high morbidity and mortality rate among the elderly. Recent improvements in surgical and anesthetic techniques, an increasing number of elderly patients, and an increasing need to justify use of limited health care resources prompted an assessment of recent surgical outcomes. METHODS: Five hundred seventy-seven liver resections (July 1985-July 1994) performed for metastatic colorectal cancer and 488 pancreatic resections (October 1983-July 1994) performed for pancreatic malignancies were identified in departmental data bases. Outcomes of patients younger than age 70 years were compared with those of patients age 70 years or older. RESULTS: Liver resection for 128 patients age 70 years or older resulted in a 4% perioperative mortality rate and a 42% complication rate. Median hospital stay was 13 days, and 8% of the patients required admission to the intensive care unit (ICU). Median survival was 40 months, and the 5-year survival rate was 35%. No differences were found between results for the elderly and those for younger patients who had undergone liver resection, except for a minimally shorter hospital stay for the younger patients (median, 12 days vs. 13 days; p = 0.003). Pancreatic resection for 138 elderly patients resulted in a mortality rate of 6% and a complication rate of 45%. Median stay was 20 days, and 19% of the patients required ICU admission, results identical to those for the younger cohort. Long-term survival was poorer for the elderly patients, with a 5-year survival rate of 21% compared with 29% for the younger cohort (p = 0.03). CONCLUSIONS: Major liver or pancreatic resections can be performed for the elderly with acceptable morbidity and mortality rates and possible long-term survival. Chronological age alone is not a contraindication to liver or pancreatic resection for malignancy.

Preoperative Radiation and Chemotherapy in the Treatment of Adenocarcinoma of the Rectum

Abstract: Objective In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group Summary Background Data The optimal treatment of large rectal carcinomas remains controversial ; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation ; the combination can be associated with significant postoperative morbidity In spite of these measures, local recurrences and distant metastases continue as serious problems Methods Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients In this group of patients, all 43 had biopsy-proven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease The patients ranged from 31 to 81 years of age (median 61 years), with a male :female ratio of 3 :1 A concurrent control group consisting of 56 patients (median : 62 years, male :female ration of 3 :2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates Results The preoperative chemoradiation therapy was well tolerated, with no major complications All patients underwent repeat sigmoidoscopy before surgery ; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months) Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months) Local recurrence was seen in only 2 of 43 patients (<5%) Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0017), increased disease-free survival (p = 0046), and decreased pelvic recurrence (p = 0031) for protocol versus control patients Conclusions This therapeutic regimen has provided enhanced local control and decreased metastases Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency