Palliation of malignant dysphagia by laser therapy.

The outcome of 211 patients undergoing laser therapy as palliation for inoperable carcinoma of the esophagus is presented. The median age was 73 (range 44-97). The histology was adenocarcinoma for 127 patients and squamous-cell carcinoma for 84 patients. For 133 patients, laser was the only therapy while 56 patients had a combination of laser therapy and radiotherapy/chemotherapy. One patient underwent laser recanalization prior to resection while four patients had recurrence after resection treated by laser. Eleven patients underwent laser therapy for recurrent dysphagia after placement of an esophageal endoprosthesis. Eighteen patients died of procedure-related complications (i.e. 9% of patients and 2% of procedures). Of 32 procedures which perforated the tumour, 10 ended in death and the remaining patients were successfully treated conservatively. Good palliation was achieved for 170 patients (80%), while 19 patients underwent intubation after failure of laser therapy. Laser therapy failed to relieve dysphagia for 22 patients. The median survival was 20 weeks with the 1-year survival 12% and 2-year survival 4%; there were no significant differences in survival dependent on histology or administration of adjuvant radiotherapy or chemotherapy. Laser therapy provides a practical alternative to intubation in the treatment of malignant dysphagia for patients with unresectable esophageal carcinoma.

Survival after peranal and abdominoperineal resection for rectal carcinoma.

The outcome of a consecutive series of 47 patients with rectal cancer treated by endoscopic transanal resection or peranal local excision was contrasted with that of 42 patients undergoing abdominoperineal resection. Surgery was considered curative for 35 and nine patients treated by abdominoperineal and peranal resection respectively (P < 0.001). Patients undergoing peranal excision were older than those treated by abdominoperineal resection (median 77 versus 69 years, P < 0.01). The 5-year survival rate of patients undergoing peranal resection was 24 per cent compared with 33 per cent for those treated by the abdominoperineal procedure (P < 0.005). When surgery was palliative the survival rate after both procedures was the same. Survival after peranal excision was significantly poorer than that after abdominoperineal resection but this may be acceptable when the stage of disease and age of the patients are taken into account.

Long-term survival after endoscopic transanal resection of rectal tumours.

The outcome and survival of 120 consecutive patients of median age 78 years with rectal tumours who underwent endoscopic transanal resection were assessed. Thirty-eight patients (32 per cent) were treated for large villous adenoma. These patients underwent a median of 2 (range 1-5) resections and the overall 5-year survival rate was 78.2 per cent. Of 82 patients with rectal cancer, 33 (28 per cent of the 120) had tumours amenable to conventional surgery but for the patient's age or infirmity. The 5-year survival rate of these patients was 29.7 per cent. Endoscopic transanal resection was used to palliate the symptoms of 49 patients (41 per cent) with rectal cancer; the 5-year survival rate was 13.7 per cent. Excellent long-term outcome may be achieved with endoscopic transanal resection for patients with benign rectal tumours. This approach also gives acceptable results for selected patients with rectal cancer in whom age, extent of disease or concurrent illness preclude conventional surgical resection.

Complications and survival of multilumen central venous catheters used for total parenteral nutrition.

In a prospective study of 879 triple-lumen catheters, 219 pulmonary artery catheters, 31 double-lumen and six single-lumen catheters used for the administration of total parenteral nutrition over a 1-year period, the overall complication rate was 12.5 per cent (14.7 complications per 1000 catheter-days) and the catheter-related sepsis rate 4.4 per cent (5.2 per 1000 catheter-days). The probability of development of catheter-related sepsis did not increase with the duration of catheterization. There were no differences in the rate of complications associated with 427 catheters changed by replacement at a new site compared with 159 lines changed over a guidewire. These data support the use of multilumen central venous catheters for the administration of total parenteral nutrition. They suggest that a routine weekly change of line is unnecessary; catheters should be changed only on the development of a complication. When it is required, a catheter should be changed by replacement over a guidewire.

Survival after hepatic resection for malignant tumours.

A retrospective analysis of 194 patients who underwent hepatic resection for primary or metastatic malignant disease from January 1962 to December 1988 was undertaken to determine variables that might aid the selection of patients for hepatic resection. Hepatic metastases were the indication for resection in 126 patients. The 5-year survival rate was 17 per cent. For patients with resected metastases from colorectal cancer (n = 104), the survival rate at 5 years was 18 per cent. The 5-year survival rate was 27 per cent when the resection margin was > 5 mm compared with 9 per cent when the margin was < or = 5 mm (P < 0.01). No patient with extrahepatic invasion, lymphatic spread, involvement of the resection margin or gross residual disease survived to 5 years, compared with a 23 per cent 5-year survival rate for patients undergoing curative resection (P < 0.02). The survival rate of patients with poorly differentiated primary tumours was nil at 3 years compared with a 20 per cent 5-year survival rate for patients with well or moderately differentiated tumours (P not significant). The site and Dukes' classification of the primary tumour, the sex and preoperative carcinoembryonic antigen level of the patient, and the number and size of hepatic metastases did not affect the prognosis. The 5-year survival rate for patients with hepatocellular carcinoma (n = 42) was 25 per cent. An improved survival rate was found for patients whose alpha-fetoprotein level was normal (37 per cent at 5 years) compared with those having a raised level (nil at 3 years) (P < 0.01). Involvement of the resection margin, extrahepatic spread and spread to regional lymph nodes were associated with an 8 per cent 5-year survival rate versus 44 per cent for curative resection (P < 0.005). The presence of cirrhosis, the presence of symptoms, and the multiplicity and size of the tumour did not affect the prognosis. The 5-year survival rate of 11 patients with hepatic sarcoma was 25 per cent. No patient with peripheral cholangiocarcinoma survived to 1 year in contrast to patients with hilar cholangiocarcinoma, all four of whom survived for more than 14 months.

Elective and emergency hepatic resection. Determinants of operative mortality and morbidity.

To determine the reasons for improved mortality and morbidity rates after major hepatic resection, five variables were analyzed retrospectively in 300 patients operated on over a 27-year period: (1) the indication for surgery, (2) the surgical approach, (3) the urgency with which surgery was performed, (4) the nature of the surgical procedure, and (5) the experience of the surgeon. The operative mortality rate decreased from 19% between 1962 and 1979 to 9.7% between 1980 and 1988 (p less than 0.05). The operative mortality rates for patients undergoing resection for benign hepatic neoplasms was 3.4%; for metastatic tumors, 6.3%; for primary hepatic malignancies, 19%; and for trauma, 33%. Fifty-seven percent of operations before 1980 were performed through a thoracoabdominal exposure as compared with 19% after 1980. Overall a thoracoabdominal exposure of the liver was associated with a 20% mortality rate as compared with 8.6% for operations with abdominal exposure of the liver (p less than 0.02). Elective operations accounted for 65% of hepatic resections before 1980, as compared with 90% after 1980, and were associated with an 8.8% mortality rate as compared with 30.7% for urgent and emergency operations (p less than 0.001). Segmental and wedge resections were associated with a 5.3% mortality rate as compared with 14.7% for major hepatic resections (p less than 0.05), but this difference did not affect overall operative mortality rates because there was no change in the proportion of major hepatic resections after 1980. Surgical experience was not a determinant of operative mortality or morbidity rates in elective operations. Although there was no reduction in the complication rate after 1980, there was a reduction in postoperative stay from 26 days before 1980 to 16 days after 1980 (p less than 0.001). A reduction in the incidence of postoperative sepsis and a change in its management was associated with improved operative mortality rates.

Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation.

Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy.

Somatostatin inhibits neutrophil elastase release in vitro.

The influence of the long-acting somatostatin analogue, SMS 201-995, on FMLP-induced neutrophil elastase release in vitro has been investigated. Doses from 150 ng/ml upwards inhibited elastase release, with 100% inhibition by 2500 ng/ml. Inhibition was demonstrated both by an assay measuring elastase immunometrically and by an assay based on its enzyme activity. The demonstration that SMS 201-995 inhibits protease release from polymorphonuclear leukocytes may have implications for the long-term clinical use of this somatostatin analogue.

Does resection enhance the response of the intestine to urogastrone-epidermal growth factor in the rat?

1. The objective of this study was to see whether another proliferative stimulus could modify the marked proliferative effect of human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) on the gastrointestinal epithelium. 2. The response of the gastrointestinal tract to URO-EGF was investigated in rats maintained on total parenteral nutrition (TPN) with or without 75% small bowel resection. 3. Continuous infusion of 60 micrograms of recombinant beta-urogastrone/day per rat increased proliferation in the stomach by over four times (P less than 0.01), doubled proliferation in the small intestine (P less than 0.001) and increased it by four and a half times in the colon (P less than 0.001) in the control group. No significant effect of urogastrone was observed in the stomach of the resected groups, but proliferation was also increased in the small intestine by one and a half times (P less than 0.001) and by nearly four times in the colon (P less than 0.001). 4. Two-way analysis of variance showed that resection had a significant effect (P less than 0.01) on proliferation below the anastomosis and in the ileum. However, the response of the ileum was only half that observed in orally fed rats, which confirms the importance of 'luminal nutrition' in the response to resection. 5. Intestinal resection in the TPN rat was associated with a small rise in plasma enteroglucagon levels, suggesting that this hormone may be implicated in the adaptive response of the small intestine to resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental colonic carcinogenesis: changes in faecal bile acids after promotion of intestinal tumours by small bowel resection in the rat.

Small bowel resection promotes the development of colonic tumours in azoxymethane treated rats. As high faecal bile acid concentrations are associated with colonic cancer and may be altered by resection, we have studied changes in faecal bile acid concentrations during promotion of colonic carcinogenesis by increasing small bowel resection. Twenty rats in each group underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg by 12 weekly subcutaneous injections, and faecal bile acid concentrations were measured at six and 16 weeks. Colonic tumour number rose from 0.6 per rat in the transection group to 1.6 per rat in the 50% resection group (p less than 0.01) but were not significantly different to transection values at 0.8 per rat in the 80% resection group. Total daily faecal bile acid excretion and bile acid concentrations fell with increasing resection from 14.2 (1.6) mg/rat/day and 5.8 (0.7) mg/g dry faeces respectively in the transection group to 6.5 (0.5) mg/rat/day and 2.9 (0.2) mg/g respectively in the 80% resection group (p less than 0.001). The greatest reduction was seen in the concentration of deoxycholic acid which has been particularly associated with the aetiology of colonic cancer. The promotion of colonic tumours following small bowel resection in carcinogen treated rats is unlikely to be mediated by changes in faecal bile acid concentration or composition.

Controlled trial of occlusive dressings in healing chronic venous ulcers.

Fifty-six patients with chronic venous ulcers present for a mean of 2.4 years were randomized to either a new occlusive hydrocolloid dressing (Granuflex, Squibb Surgicare) or a porous non-adherent dressing (N A, Johnson and Johnson). In all patients, dressings were applied beneath a standard graduated compression bandage. There was no difference between the two groups, with complete healing in 21 out of 28 (75 per cent) of occlusive dressing patients and 22 out of 28 (78 per cent) with N A dressings by 12 weeks. Careful graduated compression bandaging achieves healing even in the majority of so-called resistant chronic venous ulcers; there was no additional benefit from applying occlusive dressings which tend to be expensive.

Release of peptide YY (PYY) after resection of small bowel, colon, or pancreas in man.

To investigate the possible role of peptide YY (PYY) in the adaptive changes that accompany enterectomy, plasma levels of this peptide were measured during breakfast in patients with resected small or large intestines and in controls. In 18 patients who had undergone partial ileal resection, basal PYY concentrations were greatly elevated when compared with controls (51.4 +/- 8.7 pmol/L versus 10.3 +/- 1.0; p less than 0.001) and the postprandial response was similarly increased. In contrast, PYY concentrations were low in 16 patients who had undergone colonic resection and ileostomy (fasting 7.1 +/- 0.7 pmol/L, p less than 0.01). In eight patients who had undergone pancreatectomies, basal and postprandial PYY levels were moderately increased (23.4 +/- 3.5 pmol/L; fasting p less than 0.001). PYY does not appear to have a role in the adaptive trophic response after small intestinal resection, but it may contribute to reduction of gastric secretion and gastrointestinal transit in these patients.

Effect of a long-acting analogue of somatostatin, SMS 201-995, on the development of intestinal tumours in azoxymethane-treated rats.

The effect of daily parenteral administration of a long-acting analogue of somatostatin (SMS 201-995) on the development of intestinal tumours and the rate of crypt cell proliferation in azoxymethane-treated rats has been studied. SMS 201-995 had no significant effect on the number of colonic tumours induced. In the duodenum, SMS 201-995 administration was associated with a change in the number of tumours from 1.4/rat in saline-treated animals to 2.4/rat in animals treated for the last third of the study and 2.8/rat in animals treated with SMS for the entire duration of the study (P less than 0.02). SMS had no significant effect on the rate of cell proliferation in the duodenum, ileum or colon. The inhibition of release of gastrointestinal trophic hormones by this analogue of somatostatin thus does not appear to reduce the number of tumours in the intestine of azoxymethane-treated rats.

SMS 201-995 treatment and advanced intestinal cancer: a pilot study.

The hypothesis that somatostatin, a compound with antitrophic effects on the gastrointestinal tract, may affect beneficially the progression of advanced intestinal cancer has been tested in a small pilot study. Ten patients, four with advanced pancreatic cancer, four with advanced colorectal cancer and two with gastric cancer, were treated with a long-acting analogue of somatostatin, SMS 201-995, 50, 100 micrograms subcutaneously twice daily. There were no clinical, radiological or biochemical indicators of a response to this treatment. There are no indications from this study that hormonal manipulation alters the rate of growth of advanced gastrointestinal cancer.

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.

Enteroglucagon and experimental intestinal carcinogenesis in the rat.

To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.

Epidermal growth factor in blood.

The presence of receptors for epidermal growth factor (EGF) in a wide variety of human tissues and also some tumours indicates an as yet undefined role for EGF and it is therefore necessary to know precise concentrations in blood and other fluids. We have investigated the occurrence of EGF in the circulation and found that in platelet rich plasma, EGF levels were 51 +/- 5 pmol/l (mean +/- S.E.M., n = 6) while in platelet poor plasma levels were 2.9 +/- 0.9 pmol/1. In contrast, serum EGF was 37 +/- 7 pmol/l if separated at 30 min and rose to 117 +/- 5 pmol/l if separated at 270 min. Gel chromatography showed that all residual EGF immunoreactivity in platelet poor plasma resided in the high molecular weight form thought to be non biologically active. In serum, delay in separation resulted in an increase in the proportion of EGF immunoreactivity co-eluting with EGF standard. These results suggest that EGF in the circulation is associated with platelets and that the process of blood coagulation leads to release of free EGF.

Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.