Biomedical subjects
Publications and source records attributed to A N Kingsnorth.
The preperitoneal space is presented from an embryologic, anatomic, and surgical standpoint in detail. Because this space is one of the most used areas for the repair of groin hernias, knowledge of its embryology and anatomy is essential.
BACKGROUND: Mutations of the cationic trypsinogen gene have been detected in hereditary pancreatitis. This article reviews current understanding of their function and clinical significance. METHODS: An unrestricted Medline search was conducted using the key words hereditary pancreatitis and 'cationic trypsinogen . Additional material was obtained from references cited in original papers and recently published abstracts of meetings. RESULTS AND CONCLUSION: Cationic trypsinogen mutations have been identified in most, but not all, families with hereditary pancreatitis. This confirms existing evidence that premature trypsinogen activation plays a central role in the pathogenesis of human pancreatitis. Patients currently clinically defined as having hereditary pancreatitis should be screened for the presence of cationic trypsinogen mutations. A subgroup of patients with non-hereditary pancreatitis may also benefit from being screened for these mutations. Patients with hereditary pancreatitis should be entered into prospective, multicentre trials investigating secondary screening for pancreatic cancer. Gene therapy for hereditary pancreatitis is beyond current technological capability but remains a future therapeutic prospect for this often debilitating condition.
We present a case of a long-standing, giant inguinoscrotal hernia extending to the patient's knees, complicated by intestinal obstruction. Initial management involved conservative treatment of the intestinal obstruction and optimising the patient's general condition. Surgical treatment included debulking the contents of the hernia sac by performing a right hemicolectomy and a small bowel resection, and reconstruction of the abdominal wall using Marlex mesh and a tensor fasciae latae flap. Although abdominal wall reconstruction for massive ventral or incisional herniae is well reported, inguinoscrotal herniae of this magnitude are much rarer and pose additional problems, which are discussed in this paper.
BACKGROUND: Open mesh used in anterior inguinal hernia repair can be configured as a flat patch (Lichtenstein operation) or as a cone-shaped preformed plug and supplementary patch (plug-and-patch operation; Perfix Plug; Davol Inc, Cranston, RI). METHODS: One hundred forty-one patients were randomly allocated and blinded to receive either a Lichtenstein patch or a Perfix plug-and-patch. Information before the operation and on postoperative days 3 and 14 was recorded by an independent blinded observer to include operating time, postoperative pain, analgesic medication, return to activity and work, and quality of life assessment. RESULTS: Operating time (32 vs 37.6 minutes) was significantly shorter in the plug-and-patch group (P = .01). During days 1 through 8, patients who had undergone the plug-and-patch operation experienced less pain, and their physical functioning on day 3 was significantly better (P = .013). Days of analgesic medication (4.0 vs 4.6 days), return to normal activity (2.8 vs 3.6 days), return to work (17.0 vs 20.8 days), and total days of work missed (14.3 vs 16.1 days) were similar in both groups (P = NS for all comparisons). CONCLUSIONS: Compared with patients who received the Lichtenstein patch for ambulatory inguinal hernia repair, patients who underwent the Perfix plug-and-patch operation experienced less postoperative pain in the first 8 days after the operation but consumed similar postoperative analgesic medication. The rate of return to normal activity and work is similar in both groups, which indicates no superiority for the plug-and-patch operation in overall rehabilitation and societal costs. Overall hospital costs are greater for the plug-and-patch operation ($120 [US]) compared with the Lichtenstein patch ($20 [US]), with a negligible (5.6 minutes) saving of operating room time for the plug-and-patch operation.
The interleukin 1 (IL-1) gene cluster has been implicated in acute pancreatitis. Penta-allelic and bi-allelic polymorphisms exist in the IL-1RN and IL-1B genes, respectively. The aim of the study was to investigate these polymorphisms in acute pancreatitis. Genotype and allele frequencies were determined in patients (n = 116) and healthy controls (n = 170) using the polymerase chain reaction. PCR products from the IL-1B study were further digested with Taq I restriction endonuclease. Patients were categorised according to aetiology, severity, and organ-failure scores. Allele 1 of the IL-1RN polymorphism was significantly increased in patients compared with controls (72.0 vs. 63.0%; p = 0.029, Pc = 0.029), in severe cases compared with controls (81.9 vs. 63.0%; p = 0.002, Pc = 0.004), in idiopathics compared with controls (82.4 vs. 63.0%; p = 0.002, Pc = 0.006), and in severe cases compared with mild cases (81.9 vs. 67.5%; p = 0.023, Pc = 0.046). Allele 2 was significantly decreased in severe cases compared with controls (18.1 vs. 33.0%; p = 0.013, Pc = 0.026), in idiopathics compared with controls (17.6 vs. 33%; p = 0.013, Pc = 0.039), and in severe cases compared with mild cases (18.1 vs. 32.5%; p = 0.023, Pc = 0.046). No significant differences were found for the Taq I allele or genotype frequencies between controls and patients/subgroups of patients. IL-1RN appears to determine severity of acute pancreatitis and susceptibility to idiopathic acute pancreatitis. No association was found between IL-1B and the disease.
BACKGROUND: Reports of better results at national referral centers than at low-volume community hospitals have prompted calls for regionalizing pancreaticoduodenectomy (the Whipple procedure). We examined the relationship between hospital volume and mortality with this procedure across all US hospitals. METHODS: Using information from the Medicare claims database, we performed a national cohort study of 7,229 Medicare patients more than 65 years old undergoing pancreaticoduodenectomy between 1992 and 1995. We divided the study population into approximate quartiles according to the hospital's average annual volume of pancreaticoduodenectomies in Medicare patients: very low (<1/y), low (1-2/y), medium (2-5/y), and high (5+/y). Using multivariate logistic regression to account for potentially confounding patient characteristics, we examined the association between institutional volume and in-hospital mortality, our primary outcome measure. RESULTS: More than 50% of Medicare patients undergoing pancreaticoduodenectomy received care at hospitals performing fewer than 2 such procedures per year. In-hospital mortality rates at these low- and very-low-volume hospitals were 3- to 4-fold higher than at high-volume hospitals (12% and 16%, respectively, vs. 4%, P<.001). Within the high-volume quartile, the 10 hospitals with the nation's highest volumes had lower mortality rates than the remaining high-volume centers (2.1% vs. 6.2%, P<.01). The strong association between institutional volume and mortality could not be attributed to patient case-mix differences or referral bias. CONCLUSIONS: Although volume-outcome relationships have been reported for many complex surgical procedures, hospital experience is particularly important with pancreaticoduodenectomy. Patients considering this procedure should be given the option of care at a high-volume referral center.
Acute pancreatitis is a common disease. As knowledge of its pathophysiology improves, evidence is found to confirm and refute present management and also to suggest new approaches. This article addresses some of these areas in the context of the management of acute pancreatitis.
The symptoms of necrolytic migratory erythema, diabetes, stomatitis, weight loss and diarrhoea represent the glucagonoma syndrome which has been recognized since the early 1970s. Because of its rarity (1 case/20-200 million population) late diagnosis is frequent which leads to a poor prognosis. The case described, originally reported in 1974, is the longest survivor to be documented in the literature, and is one of the original patients with a glucagonoma that helped to define the syndrome.
The Plymouth Regional MRCS Course was initiated in 1997 to support the College STEP learning course and supplement the BST clinical training programmes. The course is a comprehensive fortnightly day-release scheme, covering, over one year in 21 full days of teaching, the entire MRCS syllabus in a structured programme of learning.
The efficacy of a surgical procedure is a measure of outcome when performed by specialists. The monotonous excellence of countless cohort studies bears witness to the efficacy of numerous techniques of herniorrhaphy. Effectiveness, however, is of far greater relevance to health care commissioners than efficacy. Audit is an instrument of effectiveness and can be further developed to study cost-effectiveness where outcomes do not differ greatly.
Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.
OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher's exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.
BACKGROUND: Serological tests for pancreatic cancer are little used, partly because such assays have proved insufficiently specific for screening. However, retrospective studies have reported results that compare well with commonly used scanning techniques. In this prospective study we assessed a new type of combined lectin/antibody enzyme-linked mucin assay, CAM 17.1, in a routine clinical setting. METHODS: Clinicians at a 1200-bed teaching hospital were encouraged to request the CAM 17.1 assay for any patient whose differential diagnosis included pancreatic cancer. Serum samples from 250 patients were tested during an 18-month period. Patients were followed up for at least 8 months. 75 patients who did not have symptoms of pancreatic cancer and had alternative diagnoses were also studied as a control group. FINDINGS: Of the 250 patients, 36 had pancreatic cancer, as defined by histological and imaging criteria, and eight of these patients had a resectable tumour. The sensitivity and specificity of the CAM 17.1 assay were 86% and 91%, respectively, in all patients, 85% and 81% in those who presented with jaundice, and 89% and 94% in patients who did not have jaundice. The sensitivity of the assay compared well with that of ultrasound scanning (59%) and computed tomography (83%) in these patients. Use of the CAM 17.1 assay in combination with ultrasonography allowed identification of 94% of patients with pancreatic tumours and all of those with resectable tumours. CAM 17.1 binding activity did not correlate with tumour size. INTERPRETATION: Our study confirms the usefulness of the CAM 17.1 tumour-marker assay for the diagnosis of pancreatic cancer. Serological mucin assays should be used more widely in combination with ultrasonography in the investigation of non-jaundiced patients with unexplained abdominal pain or weight loss.
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Helicobacter pylori (HP) plays a crucial role in gastric carcinogenesis. Few studies have looked at the relationship between HP and Barrett's esophagus/cancer. To further investigate this, a study comparing the prevalence of HP and increasing grades of dysplasia was undertaken. Biopsies from 19 malignant and 94 benign cases of Barrett's esophagus were analysed histologically for the presence of HP. 34% of non-dysplastic Barrett's epithelium was colonized with HP compared with only 17% of dysplastic/malignant cases (P = 0.04). No relationship was found between HP status and: (i) length of Barrett's esophagus; (ii) the presence of ulcers or strictures; and (iii) previous anti-reflux surgery. HP colonization of Barrett's esophagus is not uncommon. We found that HP has a negative correlation with increasing dysplasia which is analogous to gastric carcinogenesis. This finding should be investigated in prospective studies to elucidate its role in Barrett's adenocarcinoma.
BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.
The development of a single-surgeon specialist referral practice for pancreatic surgery which evolved over an 8 year period is described. Source of referral, protocol for patient management, and operative strategy are outlined. Preoperative endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy, and stent placement where possible (85% of cases), high-resolution contrast-enhanced CT and standard pylorus-preserving pancreaticoduodenectomy with a unique reconstructive technique were employed. In 105 patients receiving curative resection for pancreatic or periampullary tumours, the overall operative mortality was 4.8% and overall morbidity 26%. Actuarial 5-year survival rates were 11% for pancreatic carcinoma and 34% for ampullary carcinoma. Resectability rate was 81% without the use of time-consuming and expensive imaging techniques for staging such as laparoscopy, intraoperative ultrasound or laparoscopic ultrasound. No specific regimen of perioperative chemoirradiation was utilised over the study period. To achieve comparable results it is recommended that patients should be referred to regional specialist surgeons in whose hands mortality and morbidity is low, costs reduced and training of pancreatic surgeons can be undertaken.
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