The effects of colectomy on immediate-early proto-oncogene expression and hepatic regeneration in the rat.

The intact liver exists in a state of replicative quiescence. The factor(s) responsible for maintaining this state and their tissue sources have yet to be identified. Because the colon synthesizes and/or absorbs numerous agents that inhibit hepatocyte proliferation, the principle purpose of this study was to determine whether total colectomy would result in the conversion of quiescent livers to a state of replicative competence. Thus, adult, male Sprague-Dawley rats (250-300 g) were randomized to undergo either total colectomy with ileostomy or sham surgery. Thereafter, rats were sacrificed (N=3-6/group) at times 15 and 30 min and 1, 2, 6, and 24 hr and the livers analyzed by Northern blot analyses for mRNA of the following immediate-early proto-oncogenes (IEP genes): c-fos, c-jun, and c-myc. Rats sacrificed at 24 hr also had hepatic regenerative activity documented by [3H]thymidine incorporation into hepatic DNA. The results of the study revealed that within 15 min, c-fos and c-jun mRNA expression increased in colectomized rats, with peak expression occurring at 30 and 60 min, respectively. c-myc mRNA expression was more delayed, with peak expression occurring at 6 hr post-colectomy. IEP gene expression also increased somewhat in sham-colectomy controls but the increases were not as prompt and, in general, were of lower magnitude than those in the colectomy group. Despite the differences in IEP gene expression between the two groups, [3H]thymidine incorporation at 24 hr was similar (mean+/-SE: colectomy group, 17.2+/-2.6 dpm/microg DNA; sham-colectomy controls, 14.8+/-1.4 dpm/microg DNA). To determine whether the increases in IEP gene expression expedite or augment the hepatic regenerative response to partial hepatectomy (PHx), rats that had undergone colectomy or sham colectomy 1 hr earlier and rats with no previous abdominal surgery then underwent a 70% PHx and were sacrificed at 8, 16, and 24 hr thereafter. At each time interval, [3H]thymidine incorporation was documented and found to be similar in the three groups. In conclusion, the results of this study indicate that total colectomy, and to a lesser extent abdominal surgery, induces the conversion of an intact, quiescent liver to a state of replicative competence. The results also suggest that, in addition to colectomy, the presence of mitogens and/or co-mitogens is required for further progression of hepatocytes through the cell cycle. Finally, a "primed" liver does not respond more promptly or vigorously to a regenerative stimulus than a "resting" liver.

Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown etiology characterized by progressive fibrosis and stricturing of the biliary tract. Transforming growth factor-beta (TGF-beta) is a family of cytokines produced by biliary tract epithelial cells that promote fibrinogenesis. Our objective was to determine whether TGF-beta levels are increased in the blood and/or bile of PSC patients compared to patients with other causes of obstructed biliary tracts (controls). Serum and bile TGF-beta levels were documented by enzyme-linked immunoassay in 10 adult PSC and 10 control patients obtained at the time of endoscopic retrograde cholangiography. Serum and bile TGF-beta levels were similar in the two groups (PSC versus control sera, 33.4 +/- 4.3 versus 27.5 +/- 7.7 ng/ml, and bile, 367 +/- 275 versus 457 +/- 247 ng/mg, respectively). Serum and bile TGF-beta levels are not increased in patients with PSC. Hence, the results of this pilot study do not support the hypotheses that PSC is caused by dysregulated TGF-beta expression.

A comparison of the effect of elemental and immune-enhancing polymeric jejunal feeding on exocrine pancreatic function.

BACKGROUND: There are few studies examining the effect of jejunal feeding on pancreatic exocrine output. The purpose of this study was to compare the effects of jejunal feeding with an elemental formula (EF) and with a polymeric immune-enhancing formula (PIEF) on pancreatic exocrine function. METHODS: Patients undergoing a partial pancreatectomy had a jejunal feeding tube inserted and a pancreatic stent exteriorized, facilitating collection of pancreatic secretions. Postoperatively, patients underwent a secretin-stimulation test to document adequate pancreatic reserve. Patients were then randomized to receive jejunal feeding with EF or with PIEF for a 24-hour period, followed by a washout period of feeding with dextrose, and subsequent jejunal feeding with EF or PIEF. RESULTS: The secretin-stimulation test demonstrated significant pancreatic reserve in all patients. There was a mild increase in pancreatic exocrine secretion with jejunal feeding with EF and PIEF compared with baseline and with dextrose. There was increased bicarbonate secretion with EF compared with PIEF, but there were no other significant differences in pancreatic exocrine function. CONCLUSIONS: In this model of partial pancreatectomy, there was no significant difference in pancreatic exocrine output when use of an EF was compared with use of a PIEF for jejunal feeding. Further clinical studies are needed to determine the potential role of PIEF in pancreatic disease.

Immediate-early protooncogene expression and liver function following various extents of partial hepatectomy in the rat.

Immediate-early protooncogenes (IEP) are thought to play an important role in hepatocyte replication. Whether the extent of their expression correlates with the strength of the proliferative stimulus and subsequent regenerative activity has yet to be documented in vivo. Data are also lacking with respect to the level at which liver disease is associated with biochemical evidence of hepatic dysfunction. Thus, the objectives of this study were to determine whether a correlation exists between IEP gene mRNA expression and varying extents of partial hepatectomy (PHx) and to document the extent of resection required to result in increases in serum bilirubin levels. Eighty-nine adult, male Sprague-Dawley rats underwent either sham surgery or 20%, 35%, 55%, 70% or 90% PHx. Postoperatively, rats were killed (N = 3-6/group) at 15 and 30 mins and 8 and 24 hrs for c-fos, c-jun, and c-myc mRNA expression by northern blot analyses. Rats killed at 24 hrs also had hepatic regenerative activity documented by [3H]thymidine incorporation into hepatic DNA and serum bilirubin determinations. While c-fos mRNA expression at 15 mins and c-myc mRNA expression at 8 hrs after PHx did not correlate with the extent of PHx (r2 = 0.478 and 0.018, respectively), a weak correlation existed between c-jun mRNA expression at 30 mins and the extent of PHx (r2 = 0.662, P < 0.05). In terms of IEP mRNA expression and hepatic regenerative activity, a strong correlation existed between c-fos mRNA expression and [3H]thymidine incorporation (r2 = 0.851, P < 0.01) but not c-jun or c-myc mRNA expression. Compared to sham operated controls, [3H]thymidine incorporation was 2.0x, 3.4x, 3.2x, 7.8x, and 2.2x increased following 20%, 35%, 55%, 70%, and 90% PHx, respectively. Serum bilirubin levels remained unchanged until 70% PHx, when they increased from baseline values of 0.54+/-0.05 mg/dl to 1.02+/-0.15 mg/dl (P < 0.05). A further increase occurred following 90% PHx (1.83+/-0.30 mg/dl, P < 0.01). In conclusion these findings indicate that c-fos mRNA expression 15 mins after PHx correlates with hepatic regenerative activity but not the strength of the regenerative stimulus and that hepatic parenchymal loss of 55-70% must occur prior to the detection of elevated serum bilirubin levels. The results also indicate that relative to a 70% PHx, 90% PHx is associated with decreased rather than increased hepatic regenerative activity.

Penetrating neck injuries: analysis of experience from a Canadian trauma centre.

OBJECTIVE: To study the demographics and treatment outcome of penetrating neck injuries presenting to a major trauma centre in order to develop a treatment protocol. DESIGN: A case review. SETTING: A trauma centre at a tertiary care institution. PATIENTS: One hundred and thirty consecutive patients who had 134 neck wounds penetrating the platysma and presented to the trauma service between 1979 and 1997. INTERVENTION: Surgical exploration or observation alone. MAIN OUTCOME MEASURES: The location of injury, patient management, number of significant injuries, duration of hospital stay and outcome. RESULTS: Injuries were caused by stab wounds in 124 patients (95%) and gunshot wounds in 6 (5%). The location of injury was zone I (lower neck) in 20 cases (15%), zone II (midportion of the neck) in 108 (81%) and zone III (upper neck) in 5 (4%). The location was not recorded in 1 case. Fifty patients were managed by observation alone and 80 were managed surgically. Neck exploration in 48 asymptomatic patients was negative in 32 (67%). Significant injuries, including major vascular (12), nerve (13) and aerodigestive tract (19) injuries, were identified in 34 patients. Two of the 130 patients (1.5%) died of major vascular injuries. Seventy-six percent of significant injuries, including all zone II major vascular injuries, were symptomatic on presentation. The mean (and standard deviation) hospital stay for asymptomatic patients treated with observation alone and surgical exploration was similar (3.5 [6.02] versus 4.3 [5.46] days respectively, p = 0.575). Long-term disability, all neurologic in nature, was documented in 3 patients managed by observation alone and 6 patients managed by surgical exploration. CONCLUSIONS: Penetrating neck trauma, in particular stab wounds to zone II in asymptomatic patients, is associated with low morbidity and mortality. A selective management protocol with investigations directed by symptoms is the most appropriate approach for the patient population and resource base in this setting.

The effects of various organ preservation solutions on hepatocyte membrane potentials, intracellular calcium concentrations, and outcome following liver transplantation.

BACKGROUND: Hepatocyte membrane potential differences (PDs) may be altered by the preservation solutions used in liver transplantation. Such alterations could impact on the survival of the donor liver, extent of biochemical injury, and flux of important ionic compounds. The purpose of the present study was to document these outcomes in the presence of four different preservation solutions. METHODS: Livers of adult male Sprague-Dawley rats (N = 3 to 4 per group) were impaled with intracellular microelectrodes prior to and at various time periods for 6 hours following complete hepatic resection. Just prior to resection, each liver was perfused with preservation solutions associated with high (normal saline [NS]), moderate (Euro-Collins [EC]), and low (University of Wisconsin solution [UW]) risks of reperfusion injury. RESULTS: Baseline (in situ) PDs were similar in all groups (-37 +/- 4 mV, mean +/- SD). Ten minutes postresection, hepatic PDs were as follows: NS, -23.8 +/- 3.5 mV; EC, -11.4 +/- 0.4 mV; and UW, -8.7 +/- 0.3 mV (P <0.01 for all groups). Maximum depolarization occurred at 6 hours postresection (NS, -8.1 +/- 1.1 mV; EC, -7.7 +/- 1.3 mV; and UW, -8.6 +/- 1.0 mV). To determine whether these changes are of pathophysiologic importance, the NS solution was modified (addition of 0.1% ethanol) to achieve similar PD changes as those observed with UW. Liver transplants were then performed where the donor livers had been perfused and preserved for 6 hours with either NS or the modified NS (MNS) solution. Posttransplant (10 day) survival was 1 of 6 (17%) in the NS group and 4 of 6 (67%) in the MNS group (P <0.05). Regarding the effects of PD changes on ionic flux, intracellular calcium levels were documented for up to 4 hours by fluorescence video microscopy using Fura-2 in isolated hepatocytes exposed to NS, UW, and MNS solutions. Intracellular calcium levels were similar in all solutions at each time point studied. CONCLUSIONS: The results of this study indicate that hepatocytes undergo prompt and marked depolarization following hepatic resection, and the extent of the depolarization correlates with survival following transplantation.

Multifocal gastric neoplasia after recurrent laser therapy for the watermelon stomach.

Repeated laser therapy has become an accepted therapeutic approach in the treatment of watermelon stomach, and to date no important negative sequelae have been reported. The case of a patient who underwent repeated sessions of neodymium: yttrium aluminum garnet (Nd:YAG) laser therapy over a five-year period for the treatment of the watermelon stomach is presented. Postlaser therapy the patient developed deep ulcerations that would heal; however, he ultimately developed a nodular antrum. Random biopsies of antral nodules revealed carcinoma-in-situ. A Billroth I gastrectomy revealed two foci of carcinoma-in-situ/high grade dysplasia and multiple foci of lower grades of dysplasia. This case suggests a possible association between use of laser therapy and development of gastric neoplasia.

Successes and failures of endoscopic injection haemostasis for bleeding peptic ulcers. A prospective clinical study.

Fifty-two consecutive patients with upper gastrointestinal haemorrhage, shock (systolic blood pressure less than 100 mmHg) and a peptic ulcer showing endoscopic stigma of recent haemorrhage underwent attempts at endoscopic haemostasis. The ulcers were injected with a dilute solution of adrenaline followed by 5% ethanolamine oleate. Active bleeding was present in 22 patients (42%) at initial endoscopy. Bleeding was controlled in 40 patients (77%) in hospital. Failure occurred more frequently in duodenal ulcers than gastric ulcers (46% v. 7%; P < 0.004), and in giant (more than 2 cm diameter) duodenal ulcers (6/7) than smaller duodenal ulcers (3/15). We recommend early surgery for large posterior duodenal ulcers in preference to endoscopic injection methods.

Does endoscopic sphincterotomy prevent recurrent biliary pancreatitis?

Endoscopic sphincterotomy was electively performed as the definitive procedure on 8 high-risk patients with biliary pancreatitis; the gallbladder was left in situ. After a mean follow-up of 21 months, 2 patients had biliary symptoms for which 1 required cholecystectomy and exploration of the common bile duct. No patient developed recurrent pancreatitis during the follow-up period. When the risk of elective surgery is high, endoscopic sphincterotomy appears to protect the patient against recurrent episodes of pancreatitis, and is the initial procedure of choice for the high-risk patient with biliary pancreatitis.

Treatment of pancreatic ascites and external pancreatic fistulas with a long-acting somatostatin analogue (Sandostatin).

Prior to the advent of somatostatin conservative therapy for pancreatic fistulas, treatment included intravenous nutritional therapy with nothing per mouth and therapeutic agents to diminish pancreatic secretions. None of these modalities were uniformly successful. A prospective study to evaluate the efficacy of a long-acting somatostatin analogue (Sandostatin) was carried out. 18 patients-10 with pancreatic ascites and 8 with external pancreatic fistulas-were treated. The ascites resolved in 9 of 10 patients in a mean period of 22 days (+/- 3 days). The external fistulas were all high output fistulas and resolved in 7 of 8 patients. Mean period for closure was 23 days. There were no side effects associated with Sandostatin. Sandostatin has made a major impact on the conservative treatment of pancreatic ascites and is an important adjunct to the management of external pancreatic fistulas. It is emphasised however that surgery may be required for the underlying pancreatic disease. In this regard close surveillance of these patients is necessary.

Surgical options in the treatment of reflux oesophagitis.

Medical treatment of reflux oesophagitis requires life-long medication, does not relieve all patients of their symptoms and may not halt the progression of damage. Antireflux surgery is indicated in refluxing infants who fail to thrive, in disease uncontrolled by medical treatment or when laryngeal and pulmonary symptoms are associated with reflux. A full investigation to establish and quantitate the motility defect and severity of the reflux, nature of the refluxate and pattern of gastric emptying is necessary to plan a correct antireflux procedure which can assure a cure of up to 90% for 10 years.