Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p.

Pheochromocytomas are tumors of the adrenal medulla originating in the chromaffin cells derived from the neural crest. Ten % of these tumors are associated with the familial cancer syndromes multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and rarely, neurofibromatosis type 1, in which germ-line mutations have been identified in RET, VHL, and NF1, respectively. In both the sporadic and familial form of pheochromocytoma, allelic loss at 1p, 3p, 17p, and 22q has been reported, yet the molecular pathogenesis of these tumors is largely unknown. Allelic loss at chromosome 1p has also been reported in other endocrine tumors, such as medullary thyroid cancer and tumors of the parathyroid gland, as well as in tumors of neural crest origin including neuroblastoma and malignant melanoma. In this study, we performed fine structure mapping of deletions at chromosome 1p in familial and sporadic pheochromocytomas to identify discrete regions likely housing tumor suppressor genes involved in the development of these tumors. Ten microsatellite markers spanning a region of approximately 70 cM (1pter to 1p34.3) were used to screen 20 pheochromocytomas from 19 unrelated patients for loss of heterozygosity (LOH). LOH was detected at five or more loci in 8 of 13 (61%) sporadic samples and at five or more loci in four of five (80%) tumor samples from patients with multiple endocrine neoplasia type 2. No LOH at 1p was detected in pheochromocytomas from two VHL patients. Analysis of the combined sporadic and familial tumor data suggested three possible regions of common somatic loss, designated as PC1 (D1S243 to D1S244), PC2 (D1S228 to D1S507), and PC3 (D1S507 toward the centromere). We propose that chromosome 1p may be the site of at least three putative tumor suppressor loci involved in the tumorigenesis of pheochromocytomas. At least one of these loci, PC2 spanning an interval of <3.8 cM, is likely to have a broader role in the development of endocrine malignancies.

Fibrolamellar carcinoma as a cause of bile duct obstruction.

Obstructive jaundice due to growth within bile ducts of hepatocellular carcinoma is uncommon and usually a manifestation of advanced, lethal tumour. We report a case of fibrolamellar carcinoma of the liver presenting with obstructive jaundice, caused by tumorous permeation of the left hepatic duct with migration of tumour fragments into the common bile duct. Immunocytochemical and ultrastructural features are described. Two and a half years after complete surgical resection the patient is free of tumour. The importance of accurate diagnosis of such tumours is emphasized.

Laparoscopic surgery is safe for large adrenal lesions.

INTRODUCTION: Laparoscopic adrenalectomy has surpassed open adrenalectomy as the gold standard for excision of benign adrenal lesions. The size threshold for offering laparoscopic adrenalectomy is controversial as the prevalence of adrenocortical carcinoma increases with increasing tumour size. The aim of this paper was to assess the safety of laparoscopic adrenalectomy for large adrenal tumours (tumours > or = 60 mm). METHODS: A retrospective cohort study of patients who underwent adrenalectomy in a single unit during the period 1995-2005 was undertaken. RESULTS: One hundred and seventy patients with 173 tumours were included in this study. Of these, 29 were > or = 60 mm in size, and 16 of these patients underwent laparoscopic adrenalectomy. There were 8 adrenocortical carcinomas in the group with tumours > or = 60 mm in size. Five of these patients underwent an open adrenalectomy, while 2 and 1 patients had laparoscopic and laparoscopic converted to open adrenalectomy respectively. Four of the patients undergoing open adrenalectomy died of their disease while 1 is alive with recurrence 3 years later. The 3 patients who underwent either laparoscopic or laparoscopic converted to open adrenalectomy are alive without evidence of disease after 18 months follow up. CONCLUSION: Our data show that patients with tumours > or = 60 mm with no preoperative or intraoperative evidence of malignancy can undergo laparoscopic adrenalectomy without evidence of recurrence on short term follow up. These findings are concordant with the growing body of literature supporting laparoscopic adrenalectomy for potentially malignant tumours > or = 60 mm in size without preoperative or intraoperative features of malignancy.

Parathyroid identification by methylene blue infusion.

A preoperative infusion of methylene blue was employed in 20 patients undergoing neck exploration for hyperparathyroidism. The dye was noted to stain adenomas and hyperplastic glands a deep purple-blue colour. Normal parathyroid tissue stained to a lesser extent or not at all. All unstained parathyroid tissue was normal histologically. Methylene blue infusion is a safe method of more rapidly identifying parathyroid tissue. Its preferential staining of abnormal parathyroid tissue can assist the surgeon in deciding the extent of his parathyroid excision.

Long term nutritional effects of extensive resection of the small intestine.

A nutritional study was carried out on 36 patients several years after major resection of the small intestine (100 to 330 cm). Thirty one of these resections had been performed for Crohn's disease and only patients who had been clinically free of disease for more than one year were studied. The group of patients were 15% below their ideal weight. Total body fat was 24% below the predicted normal value and total body protein was 10% below. Although deficiencies of iron, vitamin B12 and folic acid were frequently found, only six patients were anaemic. Other vitamin and mineral deficiencies were common. Despite these abnormalities, two thirds of the patients were engaged in their normal occupation full time and were subjectively well. The others who did not regain their normal capacity for work, had a greater nutritional deficit and a shorter length of remaining small intestine. It is concluded that nutritional deficiencies are common following extensive small bowel resection and all patients need regular follow up and appropriate vitamin and mineral supplementation. However, major disturbances of body composition and severe protein energy malnutrition with a reduced capacity for work are restricted to a small number of patients with very short lengths of remaining small intestine.

A technique for the operative closure of persistent external small-bowel fistulas.

This paper presents a technique for the operative closure of persistent small-bowel fistulas. This is a radical procedure involving complete dissection of the whole of the small intestine, resection of the segment of bowel containing the fistula, and primary two-layer anastomosis. A consecutive series of 50 patients with small-bowel fistulas in presented. Twenty-three required surgery, seven of whom underwent a procedure soon after the establishment of the fistula, and in only two of these was the fistula successfully closed. The other 16 patients underwent surgery some two months after establishment of the fistula, free of sepsis and in a sound nutritional state. In fifteen patients the fistula was successfully closed, and the other has a persistent fistula which is of nuisance value only.

Hypomagnesaemia after small bowel resection: treatment with 1 alpha-hydroxylated vitamin D metabolites.

Seven patients with severe neuromuscular symptoms due to hypomagnesaemia together with hypocalcaemia following extensive resection of the small bowel were treated orally with 1 alpha-hydroxylated metabolites of vitamin D and magnesium oxide. There was a rapid response in both plasma calcium and magnesium concentrations. The mean plasma magnesium rose from 0.24 to 0.45 mmol/l with the vitamin D metabolites alone and to 0.81 mmol/l when magnesium oxide was added. The plasma calcium rose from 1.78 to 2.21 mmol/l on vitamin D alone and then remained within the normal range. This was accompanied by a rapid resolution of the neuromuscular symptoms. Such oral treatment is both acceptable to the patient and effective both for acute symptoms and in the long term to maintain plasma magnesium concentrations.

Haematemesis and Melaena: surgical management.

A prospective study of the surgical management of 100 consecutive patients with benign, non-variceal upper gastrointestinal bleeding is presented. The manner of presentation, precipitating factors, investigations and associated medical problems are discussed. Chronic duodenal ulceration was the most common cause of haemorrhage. Vagotomy and drainage with oversewing or excision of the bleeding ulcer was the surgical procedure performed in 71 of the patients in the series. The incidence of recurrent bleeding was 7%; no patient in this category required further operation. The mortality rate was 6%, and there were no deaths recorded in the patients who underwent vagotomy and drainage. The reasons for the relatively low surgical mortality are discussed.

A randomised comparison of three drainage systems following cholecystectomy.

The efficacy of low pressure, high pressure and passive drainage systems have been compared after cholecystectomy. Symptoms of pain, discomfort and nausea were compared using linear analogue scales and spirometry was used to examine pre-operative and postoperative respiratory function. The low pressure suction drain removed an intraperitoneal marker, gentamicin, more effectively than the high pressure suction drain, but not more effectively than the passive drain. There were no differences in postoperative respiratory function nor in the amount of pain or discomfort between the groups. The passive drain group reported less nausea than the suction drain groups. If a negative pressure drainage system is to be used, a low pressure suction drain should be used in preference to a high pressure system.

Angiodysplasia of the small bowel: a method of intraoperative identification.

Two cases of recurrent bleeding from the gastro-intestinal tract are described. The initial diagnosis and the identification of the lesions at laparotomy were difficult problems. In both cases the bleeding was due to a vascular lesion of the small bowel, referred to as angiodysplasia. The lesions were detected before operation by selective angiography and identified at laparotomy by a preoperative and an intraoperative injection of a vital stain through the catheter into the feeding vessels.

Surgery for recurrent peptic ulceration.

Sixty-six patients having surgery for recurrent peptic ulcers over a 10-year period are reviewed. The majority of the patients were male and developed their initial ulcers at an early age. Bleeding was the most common presenting symptom. Seventy-one percent of the recurrences occurred within three years. Barium meal X-ray examination plus endoscopy gave the correct diagnosis in 96% of cases. The causes of the recurrent peptic ulcers were: (1) incomplete vagotomy; (2) inadequate gastric resection; (3) inappropriate surgery; (4) Zollinger-Ellison syndrome; (5) gastric outflow obstruction; and (6) bile reflux. Other factors such as alcohol, analgesic abuse and psychiatric disorders were found to be common associations. Resection plus vagotomy was the summation of primary and secondary surgery in 85%. The operative mortality was 3%. Eighty-five percent of patients had a Visick grading of I or II. Only one patient had a further recurrent ulcer and this healed on medical treatment.

Effect of intestinal surgery on the risk of urinary stone formation.

The prevalence of urinary stone disease in 426 patients who had undergone bowel surgery at the General Infirmary at Leeds from 1958 to 1978 was found by postal questionnaire to be 9.4%. The risk of urinary stone formation was determined from the composition of 24 hour urines from 61 unselected patients, in whom intestinal resections had been performed. There were 27 patients with an ileostomy, 17 patients with an ileostomy and a small bowel resection, and 17 patients with a small bowel resection, or bypass, and an intact colon. Of this group of 61 patients, 9.8% gave a history of urinary stones after surgery. Compared with normal control subjects ileostomy patients had significantly lower urinary pH and volume, higher concentrations of calcium, oxalate, and uric acid, and increased risk of forming uric acid and calcium stones: a small bowel resection combined with an ileostomy increased the ileostomy output, lowered the urinary volume further, and reduced urinary calcium excretion. The concentration of urinary oxalate increased and the risk of both uric acid and calcium stones was high. Patients with small bowel resection and intact colon had hyperoxaluria and an increased risk of calcium stones despite a low urinary calcium. There was no increased risk of uric acid stones in this sub-group. It is concluded that the risk of forming urinary stones after this type of surgery is considerable. The follow-up of patients with ileostomies and with small bowel resections should include an assessment of faecal losses and urinary composition to identify the patients who have a high risk of forming urinary stones.

Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for esophageal carcinoma.

Transhiatal esophagectomy (THO) may be a valid alternative to the traditional Ivor Lewis (ILO) procedure, but there have been reservations about procedure mortality, nodal clearance, and survival. ILO is preferred for bulky midesophageal lesions and THO in frail patients, making randomization difficult. This retrospective study compares results of a 10-year period from January 1985 with a minimum follow-up period of 12 months. Four patients were lost to follow-up. Preoperative nutritional markers were similar in the two groups, as were the age and sex distribution. Altogether 33 ILOs and 65 THOs were performed. TNM staging was similar between groups, there being 43% stage II and 45% stage III lesions among the ILO patients and 53% stage II and 32% stage III disease in the THO group. Operating time was shorter for THO (256 +/- 58 minutes vs. 279 +/- 50 minutes) (p = 0.05); if two surgeons operated concurrently, THO could be performed 40 minutes quicker than THO or ILO performed by a single surgeon (p = 0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7 days for THO (p = 0.014). The 30-day mortality was 5.1%; total in-hospital mortality was 7.1% with no difference for operation type. There were similar morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no significant effect of surgical technique; there were no apparent advantages for either operation when patients were compared by tumor type or matched for stage. Hence THO is a valid alternative to ILO, particularly for stage II and III cancer.

Preoperative parathyroid identification by ultrasonic scan.

A preliminary report of the use of ultrasonic scans to locate parathyroid tissue before neck exploration is presented. Three patients suffering from hyperparathyroidism had abnormal parathyroid tissue located before surgery. These findings were confirmed at operation. The role of ultrasonic scans of the neck before exploration is discussed.