Gastrointest Surg Research Articles

Effect of Intraoperative Cholangiography During Cholecystectomy on Outcome After Gallstone Pancreatitis

Acute gallstone pancreatitis has traditionally been managed by early cholecystectomy with intraoperative cholangiography (IOC). To evaluate the effect of IOC on patient outcome, we analyzed all patients operated on for acute gallstone pancreatitis at our institution over a 3-year period. A total of 200 patients (37 open, 163 laparoscopic) were evaluated. Nineteen of 34 patients who underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) were found to have common bile duct (CBD) stones. The 59 patients who underwent cholecystectomy with IOC had significantly longer operative times compared to the 141 patients who underwent cholecystectomy alone (167 vs. 105 minutes for open [ P = 0.008] and 89 vs. 68 minutes for laparoscopic [ P < 0.0001] operations). Of the 59 patients who underwent IOC, only nine (15%) had abnormal cholangiograms, and CBD exploration in seven revealed stones in four patients, edematous ampullae in two, and no abnormality in one. Six of eight patients (5 IOC, 3 no IOC) who required immediate postoperative ERCP were noted to have CBD stones. Patients who underwent IOC had significantly longer postoperative hospital stays (3.8 vs. 2.0 days [ P = 0.007]). The incidence of retained CBD stones following surgery was similar (5.1% IOC, 2.8% no IOC). Although 7 of 122 patients who underwent laparoscopic cholecystectomy without IOC were readmitted, only one was found on ERCP to have a retained CBD stone. Age, sex, preoperative days, procedure type, and biliary-pancreatic complications after discharge did not differ significantly between patients with and without IOC. We conclude that IOC in patients operated on for acute gallstone pancreatitis results in a longer operative time and a prolonged postoperative course, but has no effect on the incidence of retained CBD stones. ( J Gastrointest Surg 2002;6:575–581.)

Systemic Response in Patients Undergoing Laparoscopic Cholecystectomy Using Gasless or Carbon Dioxide Pneumoperitoneum: A Randomized Study

In general, laparoscopic cholecystectomy produces a surgical stress response very similar to which occurs after open cholecystectomy. The question is whether the pneumoperitoneum constitutes a significant pathophysiologic trauma, which might be followed by profound changes in the stress response. We conducted a prospective, randomized trial involving 50 consecutive patients scheduled for laparoscopic cholecystectomy, who had a body mass index equal to or less than 30 kg/m 2 with no acute cholecystitis, pancreatitis, or liver or renal disease. These patients were randomized to undergo either the gasless (GLC, n = 24) or the carbon dioxide pneumoperitoneum (CLC, n = 26) procedure. Perioperative assessment of cortisol, insulin, glucose, and C-reactive protein levels was the main determinant of outcome. During the operative procedure, significantly higher levels of serum cortisol and insulin were found in the CLC group than in the GLC group ( P < 0.05). No difference in glucose levels was observed between the two groups. The inflammatory response was moderate in both groups. However, on postoperative day 1 the median C-reactive protein level was significantly higher in the GLC group than that in the CLC group ( P < 0.05). Carbon dioxide and the positive intra-abdominal pressure during conventional laparoscopy may contribute to the activation of the surgical stress response. ( J Gastrointest Surg 2002;6:582–586.)

Clinical and Histologic Follow-Up After Antireflux Surgery for Barrett's Esophagus

There are few prospective studies that document the histologic follow-up after antireflux surgery in patients with Barrett's esophagus, as defined by the recently standardized criteria. We report the clinical, endoscopic, and histologic results of patients with Barrett's esophagus followed postoperatively for at least 2 years. Diagnosis of Barrett's esophagus required preoperative endoscopic evidence of columnar-lined epithelium in the esophagus and a biopsy demonstrating specialized intestinal metaplasia, which stains positively with Alcian blue stain. Between April 1993 and November 1998, a total of 104 patients meeting these criteria underwent fundoplication (laparoscopic [n = 84] or open [n = 6] nissen, laparoscopic Toupet [n = 11], laparoscopic Collis-Nissen [n = 1], Collins-Toupet [n = 1] or open Dor [n = 1]). Short-segment Barrett's esophagus (length of intestinal metaplasia <3 cm) was found preoperatively in 34% and low-grade dysplasia in 4% of patients. All patients were contacted yearly by mail, phone, or clinic visit. At a mean follow-up of 4.6 years (range 2 to 7.5 years), 81% of patients had stopped taking antisecretory medications and 97% were satisfied with the results of their operations. Eight patients have undergone reoperation for recurrence of symptoms. Two patients have died and two were excluded from endoscopic biopsy because of portal hypertension. Sixty-six patients complied with the surveillance protocol, and their histologic results were returned to our center. Symptomatic follow-up of the 34 patients who refused surveillance esophagogastro and duodenoscopy revealed two patients who were taking medication for reflux symptoms. None of the patients have developed high-grade dysplasia or esophageal carcinoma during surveillance endoscopy (337 total patient-years of follow-up). The incidence of regression of intestinal metaplasia to cardiac-fundic–type metaplasia after successful antireflux surgery is greater than previously reported. We suspect that this is a result of longer follow-up and the inclusion of patients with short-segment Barrett's esophagus. A substantial number of patients with Barrett's esophagus who are asymptomatic after antireflux surgery refuse surveillance endoscopy. ( J Gastrointest Surg 2002;6:532–539)

Factors Affecting Surgical Risk in Elderly Patients With Inflammatory Bowel Disease

The operative treatment of elderly patients with inflammatory bowel disease (IBD) has often been avoided in favor of medical management because of a perceived increase in surgical risk. This study sought to define the following in the elderly IBD patient population: (1) the risk of surgical management and (2) those factors affecting risk. Thirty patients with IBD, aged 60 years or more, who were surgically managed by a single surgeon over a 10-year period, were retrospectively matched to 75 patients with IBD who were less than 60 years of age; patients were matched according to sex, date of surgery, and type of surgery performed. Regression analysis using generalized estimating equation methodology to account for the matched clusters of patients was performed to evaluate the effect of age group on the complication rate, operating room time, and length of hospital stay. Presence of comorbid conditions, surgical indications, prior surgery for IBD, and the use of immunosuppressive medications were studied in multivariate models, adjusting for age group. By means of univariate analysis, the odds of complications in elderly IBD patients were shown to be statistically higher than the odds seen in younger patients (47% vs. 20%, P = 0.01). Also observed in the elderly group were a longer length of hospital stay (11.5 days vs. 7.1 days, P = 0.001) and longer operating room time (249 minutes vs. 212 minutes, P = 0.02). Multivariate analysis revealed that the effect of age remained statistically significant, even when adjusted for potential confounding variables such as comorbidity, medications, date of diagnosis of IBD, and indications for surgery. The complication outcome was significantly associated with the surgical indication, with obstruction, fistula, and bleeding having increased odds of complications as compared with other indications (odds ratio = 1.7 vs. 4.2 vs. 7.2, respectively, P = 0.02). The length of hospital stay similarly was significantly associated with the surgical indication (fistula, 10.5 days vs. bleeding, 9.8 days vs. obstruction, 7.4 days vs. other, 9.3 days; P = 0.04) and a history of prior surgery. A significant interaction for length of hospital stay was present between age group and prior surgery status (with prior surgery: old, 18 days vs. young, 6.4 days, P = 0.0001; without prior surgery: old, 9.5 days vs. young 7.3 days, P = 0.10). Elderly patients with IBD have an increased rate of postoperative complications along with an increased length of hospital stay and increased operating room time. This effect of age persists when adjusted for comorbidity and immunosuppressive therapy. Complications are most dependent on surgical indications, with obstruction being the least and bleeding the worst predictive factors. The longest hospital stay is associated with patients who require surgery for fistulous disease and patients who have undergone previous surgery. The fact that the higher complication rate seen in older patients with IBD is associated with disease-defined surgical indications suggests that IBD in elderly patients may be more aggressive than what is observed in younger individuals. ( J Gastrointest Surg 2002;6:606–613.)

Use of a Bipolar Vessel-Sealing Device for Parenchymal Transection During Liver Surgery

Most blood loss during liver resection occurs during parenchymal transection, and multiple approaches have been developed to limit blood loss. The purpose of this study was to evaluate a new bipolar vessel-sealing device in hepatic surgery, particularly whether the device would permit safe transection without routine inflow occlusion. Twenty-seven hepatic procedures were performed using the device after preliminary studies to adapt its use to the liver. Inflow occlusion was used when necessary to control blood loss but not as a routine. The device worked well for transection through normal liver during common liver operations such as right hepatectomy. It worked less well for enucleations. Inflow occlusion was used in approximately 10% of resections, exclusive of enucleations, and about 25% of these patients were transfused during surgery or in the postoperative period. We conclude that the device is a useful tool in standard liver resections. ( J Gastrointest Surg 2002;6:569–574)

An Unusual Case of Squamous Cell Carcinoma Arising at the Stomal Site: Case Report and Review of the Literature

An unusual case of squamous cell carcinoma arising at the ileocutaneous stomal site is reported. The presenting symptoms were peristomal ulceration and bleeding. The patient was treated with wide local excision of the stoma and the peristomal skin, and relocation of the ileostomy. A search of the literature for other similar cases subsequently identified two additional cases that were reported in the literature in 1987 and 2000. ( J Gastrointest Surg 2002;6:630–631.)

Detecting Blunt Pancreatic Injuries

Pancreatic injury after blunt abdominal trauma is exceedingly uncommon, occurring in less than 5% of major abdominal injuries. When blunt pancreatic injury does occur, however, it is notoriously difficult to identify. The use of serum amylase has been advocated in the diagnosis of such injury, yet it is neither sensitive nor specific. Computed tomography has become widely accepted in the evaluation of hemodynamically stable patients after blunt abdominal trauma, although it is clearly not a sensitive modality for the detection of pancreatic injury. In fact, numerous examples of normal CT scans with missed pancreatic injury have been documented. However, careful attention to CT technique and awareness of the CT manifestations of pancreatic injury may facilitate the diagnosis of pancreatic injury. Additionally, important information about the pancreatic duct can be obtained with the use of MRI-pancreatography or endoscopic retrograde pancreatography. Accurate, timely identification of major pancreatic ductal injury is imperative because delay in diagnosis and associated vascular injuries are largely responsible for the high morbidity and mortality associated with blunt pancreatic trauma. Blunt pancreatic trauma can be managed successfully by means of both operative and selective approaches. ( J Gastrointest Surg 2002; 6:587–598.)

Influence of Functional Bowel Disease on Outcome of Surgical Antireflux Procedures

Patients with gastroesophageal reflux disease (GERD) have a coexisting diagnosis of functional bowel disease (FBD) in approximately 30% of cases. Symptom improvement after surgical therapy for GERD may be less in patients with FBD when compared to patients without this coexisting problem. A retrospective review of patients undergoing Nissen fundoplication between 1996 and 2000 evaluated patients with documented FBD or FBD symptoms to determine operative outcome. Poor postoperative outcome included recurrent heartburn, gas bloat syndrome, dysphagia requiring reoperation or dilation, or delay in resumption of normal diet. Bivariate comparison and multivariate logistic regression evaluated the independent impact of a documented diagnosis of FBD or preoperative symptoms of FBD on outcome. This study examined 155 patients: 32% reported having symptoms of FBD and 10% had a confirmed diagnosis of FBD. Poor postoperative outcomes occurred in 27%. Patients with a documented diagnosis of FBD were significantly more likely to have a poor outcome when compared to patients without symptoms of FBD (53% vs. 23%, P = 0.01). Patients with preoperative symptoms of FBD (but without a documented diagnosis of FBD) also had a higher incidence of poor outcome (5% vs. 23%, P = 0.09). Patients with FBD are at increased risk of poor results after antireflux surgery. Patients with these conditions should be counseled preoperatively regarding the potential for recurrent postoperative symptoms. ( J Gastrointest Surg 2002;6:632–637.)

Reduction of Intestinal Neoplasia With Adenomatous Polyposis Coli Gene Replacement and COX-2 Inhibition Is Additive

Mutations of the adenomatous polyposis coli (APC) gene are implicated early in colorectal tumorigenesis. Restoration of normal APC expression through gene therapy may prevent or reduce intestinal neoplasia. Furthermore, the relationship between colorectal tumors and increased cyclooxygenase-2 (COX-2) activity provides a rationale for the use of selective COX-2 inhibitors such as rofecoxib (Vioxx) to prevent the formation of polyps. This study was performed to determine the effects of liposome-mediated APC gene therapy and a selective COX-2 inhibitor on intestinal neoplasia in vivo. Five-week-old Min mice weaned on a 30% high-fat diet were randomized to receive no treatment (control), APC only, Vioxx only, and APC/Vioxx. APC-treated mice received a plasmid containing the human APC cDNA (pCMV-APC) mixed with a liposome preparation that was administered biweekly. Vioxx was administered at 200 ppm in the high-fat rodent chow. The control mice were treated similarly with a plasmid construct lacking the APC gene. Confirmation of exogenous APC gene expression was determined by Western blot analysis. After 2 months, there was a 54% and 70% reduction in the total number of intestinal polyps after APC and Vioxx treatment, respectively. Combined APC/Vioxx therapy reduced polyp formation by 87%. The reduction of intestinal neoplasia by APC gene replacement and COX-2 inhibition suggests their separate roles in intestinal tumorigenesis. Each modality, both individually and together, may prove therapeutic and therefore contribute to new strategies in the prevention and treatment of colorectal cancer. ( J Gastrointest Surg 2002;6:563–568.)

Poor Outcome and Quality of Life in Female Patients Undergoing Secondary Surgery for Recurrent Peptic Ulcer Disease

Secondary peptic ulcer surgery is uncommon given the success of a wide variety of medical therapies, plus the good outcome expected after primary peptic ulcer surgery. Early reports of secondary peptic ulcer surgery in the 1950s and 1960s suggested good long-term outcome in most patients; however, recent data suggest that patients operated in the Helicobacter pylori era have a worse outcome. We have attempted to quantify the poor outcome in these patients and measure the effect of sex, a previously unrecognized risk factor for poor outcome after peptic ulcer surgery. We reviewed the outcomes of 35 patients who underwent secondary peptic ulcer surgery for symptoms of persistent or recurrent peptic ulcer symptoms or complications of the condition. These patients were compared to a “control” group of patients to determine long-term quality of life as measured by the SF-36 and Visick scores (average follow-up 60 months). Visick and SF-36 scores were obtained through telephone interviews. The two groups of patients were age matched to eliminate age as a variable in the SF-36 results. There were more females than males in the secondary peptic ulcer surgery group (4.5/1 female-to-male ratio). Although perioperative mortality was zero for both groups, patients undergoing secondary peptic ulcer surgery had a high number of complications (57% of patients had complications). Patients undergoing secondary peptic ulcer surgery scored lower in seven of the eight subclasses of the SF-36 questionnaire compared to their age-matched cohorts. In contrast, average Visick scores showed slight improvement for three out of four symptoms reported. Immediate postoperative complications were not related to long-term quality of life issues. Secondary peptic ulcer surgery is more prevalent in females than in males. Although secondary peptic ulcer surgery is partially effective in alleviating symptoms, quality of life is poor. ( J Gastrointest Surg 2002; 6:396–402.)

Specific Reversible Stimulation of System y +l-Arginine Transport Activity in Human Intestinal Cells

l-Arginine, which is intimately involved in cellular immune functions and nitric oxide biology, is transported by intestinal cells largely via transport System y +. The gut epithelium is exposed to various luminal amino acids at any given time, and therefore the purpose of this study was to study the regulation of luminal arginine transport by other amino acids. System y + l-arginine transport activity was measured in Caco-2 monolayers exposed to various amino acids. l-arginine and/or other System y + substrates specifically upregulated System y + transport activity twofold after 1 hour, with a response noted as early as 5 minutes. Non–System y + substrates did not affect l-arginine absorption. Kinetic analysis indicated that l-arginine exposure increased both System y + K m and V max. Neither cycloheximide nor actinomycin affected this stimulation, indicating that the regulation did not involve transcription or translation. The System y + substrate activation effect was reversible. l-arginine transport activity returned to baseline within 3 hours when cells were reincubated in amino acid–free media. These data indicate that System y + arginine transport activity is rapidly and reversibly activated by System y + substrates via a mechanism consistent with transmembrane stimulation. These findings identify a mechanism by which luminal nutrients regulate arginine uptake by the gut. ( J Gastrointest Surg 2002;6:379–386.)

Perioperative Matrix Metalloproteinase Inhibition Therapy Does Not Impair Wound or Anastomotic Healing

Matrix metalloproteinases (MMPs) catalyze the degradation of collagen and extracellular matrix. They play a role in pathologic states including malignancy, in which they facilitate invasion and metastasis. MMP inhibition has been shown to block neoplastic invasion and improve survival in animal models of malignancy. Concern about the effects of MMP inhibitors on wound and anastomotic healing may limit their potential use in the perioperative period to prevent local and systemic showering of cancer cells from surgical manipulation. We sought to assess the safety of perioperative administration of an MMP inhibitor (BB-94) with respect to skin and bowel healing in a rat model. Absorption of BB-94 was confirmed through high-pressure liquid chromatography and mass spectroscopy of sera from treated animals. Bowel bursting pressure in all animals increased almost 10-fold between 4 and 14 days. Two-way analysis of variance showed no significant difference in bowel bursting pressure between control and treatment animals over time. There was a significant increase in the collagen content of skin specimens of all animals combined between 4 and 28 days. Similarly, all animals showed an increase in bowel collagen between 4 and 28 days. There was no significant difference in skin or bowel collagen concentrations between control and treatment animals over time. Perioperative treatment with MMP inhibition does not impair wound or enteric healing in a rat model of laparotomy and small bowel resection. MMP inhibitors are safe for use as adjuvant therapy after resection for cancer. ( J Gastrointest Surg 2002;6:488–495.)

Ongoing Deficits in Resident Training for Minimally Invasive Surgery

Patient preference has driven the adoption of minimally invasive surgery (MIS) techniques and altered surgical practice. MIS training in surgical residency programs must teach new skill sets with steep learning curves to enable residents to master key procedures. Because no nationally recognized MIS curriculum exists, this study asked experts in MIS which laparoscopic procedures should be taught and how many cases are required for competency. Expert recommendations were compared to the number of cases actually performed by residents (Residency Review Committee [RRC] data). A detailed survey was sent nationwide to all surgical residency programs (academic and private) known to offer training in MIS and/or have a leader in the field. The response rate was approximately 52%. RRC data were obtained from the resident statistics summary report for 1998–1999. Experts identified core procedures for MIS training and consistently voiced the opinion that to become competent, residents need to perform these procedures many more times than the RRC data indicate they currently do. At present, American surgical residency programs do not meet the suggested MIS case range or volume required for competency. Residency programs need to be restructured to incorporate sufficient exposure to core MIS procedures. More expert faculty must be recruited to train residents to meet the increasing demand for laparoscopy. ( J Gastrointest Surg 2002;6:501–509.)

Laparoscopic Antireflux Surgery With Routine Mesh-Hiatoplasty in the Treatment of Gastroesophageal Reflux Disease

One of the most frequent complications after laparoscopic antireflux surgery is intrathoracic migration of the wrap (“slipped” Nissen fundoplication). The most common reasons for this are inadequate closure of the crura or disruption of the crural closure. The aim of this prospective study was to evaluate surgical outcomes in patients who underwent laparoscopic antireflux surgery with simple nonabsorbable polypropylene sutures for hiatal closure in comparison to patients who underwent routine mesh-hiatoplasty. Between 1993 and 1998, a group of 361 patients underwent primary laparoscopic Nissen or Toupet fundoplication with the use of simple nonabsorbable polypropylene sutures for hiatal closure. Since December 1998, in all patients (n = 170) who underwent laparoscopic antireflux surgery, a 1 × 3 cm polypropylene mesh was placed on the crura behind the esophagus to reinforce them. Functional outcome, symptoms of gastroesophageal reflux disease, and postoperative complications such as recurrent hiatal hernia with or without intrathoracic migration of the wrap have been used for assessment of outcomes. In the initial series of 361 patients, postoperative herniation of the wrap occurred in 22 patients (6.1%). Of these 22 patients, 17 of them (4.7%) had to undergo laparoscopic redo surgery. The remaining five patients were free of symptoms. In comparison to these results, in a second group of 170 patients there was only one (0.6%) who had postoperative herniation of the wrap into the chest. There have been no significant differences in objective data such as DeMeester scores or lower esophageal sphincter pressure between the two groups. Postoperative dysphagia was increased during the early period after surgery in patients undergoing mesh-hiatoplasty but resolved without any further treatment within the first year after laparoscopic antireflux surgery. We concluded that routine hiatoplasty with the use of a polypropylene mesh is effective in preventing postoperative herniation of the wrap and leads to a significantly better surgical outcome than closure of the hiatal crura with simple sutures, without any additional long-term side effects. ( J Gastrointest Surg 2002;6:347–353.)

Age-Associated Changes in Gene Expression Patterns in the Liver

Aging is one of the least clearly understood biological processes. Alteration of oxidation/reduction (redox) enzymes has been demonstrated with aging; however, a systematic analysis of expression patterns has not been performed. The liver plays a key role in homeostasis and detoxification; therefore alteration of hepatic gene expression with aging may affect outcome after surgery. The purpose of our study was to assess changes in gene expression patterns in aged livers from both rats and humans using gene array analysis. Total RNA was extracted from young (2-month-old) and aged (2-year-old) rat livers, as well as young (1-year-old) and aged (78-year-old) human livers. Gene expression patterns were compared using Affymetrix GeneChip arrays. The expression pattern of selected genes was confirmed by reverse transcription–polymerase chain reaction. A threefold or greater change in gene expression was noted in 582 genes in the aged rat livers and 192 genes in the aged human livers. Comparison of the genes that were increased with aging demonstrated some similar patterns of expression in the rat and human livers, particularly in members of the antioxidant family and the cytochrome P-450 genes. Our findings demonstrate changes in the expression pattern of genes in the liver with aging. Concomitant increases in the expression of important antioxidant and detoxifying genes were noted in the livers of both rats and humans. This induction pattern suggests a complex link between changing hepatic detoxification/redox capability and senescence. ( J Gastrointest Surg 2002;6:445–454.)

Impact of Journal Articles and Grand Rounds on Practice: CT Scanning in Appendicitis

The purpose of this study was to determine whether a report in a high-impact journal published in January 1998 changed practice patterns and to further explore the impact of a review of the subject in a department of surgery grand rounds (January 2000). Charts from all patients undergoing appendectomy at our institution during three time periods (January to December 1997, January to December 1999, and January to June 2000) were reviewed. Rates of CT scanning, negative appendectomy, and perforated/gangrenous appendicitis were compared for the three periods to determine the impact of the journal article and the subject review during grand rounds on practice patterns and outcomes. Charts from 230 (88%) of 262 patients who underwent appendectomy during the time periods were available for review. Age, percentage of male patients, temperature on admission, and white blood cell count did not differ among the groups. The rate of CT scanning increased significantly from 1997 to 1999 and again in 2000 (6.7%, 43%, and 70%, respectively; P < 0.001), whereas the proportion of perforated/gangrenous appendicitis decreased significantly from 33% in 1997 and 31% in 1999 to 13% in 2000 ( P = 0.012). The use of CT scanning in appendicitis increased both after publication of a report in a high-impact journal and after review during grand rounds. A rate of CT scanning above 45% appeared to affect outcomes as well. ( J Gastrointest Surg 2002;6:338–341.)

Glutathione S–Transferase-Pi Expression Is Downregulated in Patients With Barrett's Esophagus and Esophageal Adenocarcinoma

The glutathione S–transferases (GSTs) are a family of enzymes that play an important role in the prevention of cancer by detoxifying numerous potentially carcinogenic compounds. GSTs conjugate reduced glutathione to a variety of electrophilic and hydrophobic compounds, converting them into more soluble, more easily excretable compounds. Decreased glutathione S–transferase-pi (GSTPI) enzyme activity has been reported in Barrett's esophagus, and an inverse correlation was demonstrated between GST enzyme activity and tumor incidence in the gastrointestinal tract, but the role of GSTPI messengerRNA (mRNA) expression in Barrett's esophagus and associated adenocarcinomas is uncertain. The purpose of this study was to investigate the role of GSTPI mRNA and protein expression in the development and progression of the Barrett's metaplasia-dysplasia-adenocarcinoma sequence, and to investigate the potential of GSTPI quantitation as a biomarker in the clinical management of this disease. GSTPI mRNA expression levels, in relation to the housekeeping gene β-actin, were analyzed using a quantitative real-time reverse transcription–polymerase chain reaction method (TaqMan) in 111 specimens from 19 patients with Barrett's esophagus without carcinoma (BE group), 21 patients with Barrett's-associated adenocarcinoma (EA group), and a control group of 10 patients without evidence of Barrett's esophagus or chronic gastroesophageal reflux disease. GSTPI mRNA expression was detectable in all 111 samples investigated. Analyzed according to histopathologic group, the median GSTPI mRNA expression was highest in normal squamous esophagus epithelium, intermediate in Barrett's esophagus, and lowest in adenocarcinoma tissues ( P < 0.001). The median GSTPI expression was significantly decreased in Barrett's esophagus tissues compared to matching normal squamous esophagus from either the BE group ( P = 0.001) or the EA group ( P = 0.023). GSTPI expression levels in adenocarcinoma tissues were decreased compared to matching normal esophagus tissues from the patients with adenocarcinoma ( P = 0.011). Furthermore, GSTPI mRNA expression values were significantly different between metaplastic, dysplastic, and adenocarcinoma tissues ( P = 0.026). GSTPI expression levels were also significantly lower in histologically normal squamous esophagus tissues from patients with cancer (EA group) compared to both normal esophagus tissues from patients without cancer (BE group; P = 0.007) and normal esophagus tissues from the control group with no esophageal abnormality ( P = 0.002). GSTPI protein expression was generally highest in the basal layer of normal squamous esophagus epithelium and lowest in adenocarcinoma cells, with Barrett's cells showing intermediate staining intensity. Our results show that downregulation of GSTPI expression is an early event in the development of Barrett's esophagus and esophageal adenocarcinoma. Loss of GSTPI expression may have an important role in the development and progression of this disease. ( J Gastrointest Surg 2002;6:359–367.)

One Hundred Consecutive Cases of Sentinel Lymph Node Mapping in Early Colorectal Carcinoma: Detection of Missed Micrometastases

Almost one third of patients with “node-negative” colorectal carcinoma (CRC) develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. We have coupled sentinel lymph node mapping and a focused pathologic examination to detect occult nodal micrometastases in CRC. Since 1996, sentinel lymph node mapping has been performed in 100 consecutive patients undergoing colectomy for CRC. Peritumoral injection of 0.5 to 1.0 ml of isosulfan blue dye was performed to demonstrate the sentinel node(s). All lymph nodes in the resection specimen were examined by routine hematoxylin and eosin staining. In addition, a focused examination of multiple sections of the sentinel nodes was performed using both hematoxylin and eosin and cytokeratin immunohistochemical analysis (CK-IHC). Overall, lymphatic mapping successfully demonstrated one to four sentinel lymph nodes in 97 (97%) of 100 patients. These sentinel nodes accurately reflected the status of the nodal basin in 92 (95%) of 97 patients. All five of the false negative cases occurred in T3/T4 tumors, and three of the five occurred during the first 30 cases in the experience. Unexpected lymphatic drainage was encountered in eight patients (8%) and altered the operative approach. Twenty-six patients were node positive by routine hematoxylin and eosin staining. Of the remaining 74 patients with hematoxylin and eosin–negative nodes, an additional 18 patients (24%) were upstaged by identification of occult nodal micrometastases that were missed on routine hematoxylin and eosin staining but detected on multiple sections (n = 5) or by CK-IHC (n = 13). The sentinel lymph nodes were the only positive nodes in 19 cases. Sentinel lymph node mapping may be performed in CRC with a high degree of success and accuracy. A focused pathologic examination of the sentinel node detects micrometastatic disease that is missed by conventional techniques in a significant proportion of patients with early CRC. Further studies are necessary to elucidate the clinical relevance of these micrometastases. ( J Gastrointest Surg 2002;6:322–330.)

Pancreatic Elastase Induces Liver Injury by Activating Cytokine Production Within Kupffer Cells via Nuclear Factor-Kappa B

Liver injury is a manifestation of the systemic inflammatory response during acute pancreatitis. We have demonstrated that elastase induces macrophage tumor necrosis factor (TNF) production in distant organs, thus mimicking pancreatitis-associated organ injury. The aim of this study was to determine the mechanism by which elastase induces hepatic cytokine production. Rat livers (n = 40) were perfused with elastase ± gadolinium (Gd) to inhibit Kupffer cells. Liver parenchymal enzymes and TNF were measured in the effluent. In vitro, rat hepatocytes or Kupffer cells were treated with elastase (1 U/ml) ± Gd (0.5 mg/ml) or pyrrolidine dithiocarbamate (PDTC; 0.5 mg/ml). TNF protein, TNF messenger RNA, and NF–κB activation were determined. In vivo, Gd blunted the elastase-induced TNF production and decreased AST, ALT, LDH, and nonviable cells (propidium iodide) ( P ≤ 0.03 vs. elastase). In vitro, elastase induced TNF production from Kupffer cells ( P < 0.001 vs. control) but not from hepatocytes. Gd or PDTC significantly attenuated the elastase-induced TNF production ( P < 0.001). Elastase-induced overexpression of TNF messengerRNA and activation of NF-κB was attenuated by Gd. Pancreatic elastase induces a pattern of liver injury similar to that seen during acute pancreatitis by activating cytokine production and gene expression within Kupffer cells via NF-κB. Gd exhibits a protective effect against elastase-induced liver injury by inhibiting activation of NF-κB. ( J Gastrointest Surg 2002;6:474-480.)

Epidermal Growth Factor Regulation of System L Alanine Transport in Undifferentiated and Differentiated Intestinal Caco-2 Cells

Epidermal growth factor (EGF) in intestinal lumen regulates many gut epithelial cell functions. Influenced by growth factors at various differentiation stages, enterocytes execute the major task of absorbing nutrient amino acids. The purpose of this study was to investigate the effects of EGF on Na +-independent L-alanine transport in intestinal epithelial cells. Na +-independent [ 3H]-L-alanine transport was measured in the differentiating Caco-2 cells. In both the undifferentiated and differentiated states, L-alanine uptake occurred via a single saturable Na +-independent system L plus simple passive diffusion. System L activity decreased as the cells progressed from the undifferentiated to the differentiated state. Prolonged incubation with EGF (>30 hours) resulted in a 70% increase in system L activity in both undifferentiated and differentiated cells. EGF stimulated the system L V max without affecting K m. System L activity stimulation was inhibited by chelerythrine chloride, cycloheximide, or actinomycin D. These data suggest that intestinal epithelial cell differentiation is associated with a decrease in system L transport capacity. EGF activates system L transport activity through a signaling mechanism involving protein kinase C, independent of cell differentiation state. Both cell differentiation and EGF regulation of system L activity occur via alteration of functional copies of the system L transporter. ( J Gastrointest Surg 2002;6:410–417.)