Surgical management of perforated peptic ulcer disease.

BACKGROUND: Surgery for perforated peptic ulcer disease is one of the most common emergency procedures carried out in the western world. The role of postoperative empiric Helicobacter Pylori eradication therapy is controversial. METHODS: The clinical, operative and postoperative surveillance details of 84 consecutive patients who underwent surgery for perforated peptic ulcer were reviewed. RESULTS: All patients underwent omentopexy +/- simple closure followed by proton pump therapy. Patients were followed-up for an average of 44 +/- 19 months. Females were older than male patients (59 +/- 20 vs. 46 + 17 years; p<0.05), presented with symptoms of a longer duration (17.9 +/- 16 vs. 8.9 +/- 9 hours; p=0.045) and had a higher mortality rate (18% vs 3%; p<0.05). Seventy-nine per cent of patients received postoperative empiric Helicobacter Pylori eradication therapy. CONCLUSIONS: Surgery for perforated peptic ulcer is associated with a significant perioperative mortality rate. Elderly female patients are particularly at risk.

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.

Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma.

The Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis. WT1 allelic integrity was examined by loss of heterozygosity (LOH) studies in formalin-fixed, paraffin-embedded (FFPE) ductal carcinoma in situ (DCIS, n = 20) and fresh frozen primary invasive breast carcinomas (n = 24). Loss of heterozygosity (LOH) at the WT1 locus (11p13) was examined by PCR evaluation of an Hinf1 restriction fragment length polymorphism (RFLP) and correlated to tumor stage (in situ and invasive). After identification of the heterozygous/informative breast lesions, 1 of 12 (8.3%) DCIS (high-grade micropapillary) and 3 of 14 (21.4%) of infiltrating carcinomas (high grade) showed loss of one allele, suggesting that LOH of the WT1 locus is a rare genetic event in early breast cancer, becoming more common in invasive and in high-grade lesions.

Cardiorespiratory effects of laparoscopy with and without gas insufflation.

BACKGROUND: Patients who are undergoing laparoscopic procedures can present with a number of ventilatory and circulatory problems. The use of a gasless technique for performing a laparoscopy by using a mechanical lifting device may potentially avoid such problems. OBJECTIVE: To compare the cardiorespiratory effects of laparoscopy with and without gas insufflation. METHODS: Twelve adult pigs were randomized to undergo a laparoscopy by using either carbon dioxide insufflation or mechanical elevation. Full invasive monitoring was performed preoperatively and at 10-minute intervals throughout the operative period. Parameters that were measured included blood gas determinations, mean arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output, stroke volume, and total peripheral resistance. RESULTS: Carbon dioxide insufflation unlike mechanical elevation led to a fall in PO2 and absorption of a significant quantity of CO2, resulting in hypercapnia, acidosis, and a consequent hyperdynamic circulation. CONCLUSION: These findings have significant implications for the use of CO2 insufflation for laparoscopy in patients with a compromised respiratory or cardiac status.

Superoxide radical and xanthine oxidoreductase activity in the human heart during cardiac operations.

BACKGROUND: The results of clinical trials of xanthine oxidoreductase inhibition in cardiac surgery are encouraging, although studies have failed to localize the enzyme to the human heart and to localize free radical activity to fresh human heart. METHODS: We adapted a histochemical staining technique based on the reduction of nitro blue tetrazolium to formazan by superoxide radical. In six samples of right atrium graded blindly on a scale of 0 through 4, strong staining (median grade, 3) of the microvasculature was seen. This was blocked by allopurinol in paired sections (median grade, 1; p < 0.01). Chemiluminescence can be used as an index of superoxide radical activity. Atrial samples were taken from 13 patients at five time points during coronary bypass grafting and placed in buffered luminol. Then chemiluminescence was measured. RESULTS: A 15-fold rise in chemiluminescence (295.93 +/- 39.47 mV) was demonstrated during reperfusion compared with the control value (19.06 +/- 0.47 mV). Chemiluminescence at 1 minute after release of the cross-clamp was significantly higher (p < 0.05) by analysis of variance versus values obtained before bypass and 1 minute before and 30 minutes after reperfusion. CONCLUSIONS: In this study we have identified superoxide radical activity and a possible generating system (xanthine oxidoreductase) in the human heart.

Screening for breast cancer in Ireland: the Eccles Breast Screening Programme.

The Eccles Breast Screening Programme is a population-based screening programme for breast cancer, based at the Mater Misericordiae Hospital, Dublin. It began in 1989 simultaneously with similar programmes in Belgium, France, Greece, Portugal and Spain. The objectives of the Eccles Programme are: (i) to evaluate the impact of mammographic screening on morbidity and mortality from breast cancer in Irish women; and (ii) to address the feasibility and potential value of a national breast cancer screening programme. The specific group targeted for screening is women born in 1925 to 1940 inclusive, in a defined geographical area comprising north Dublin City and County, and Counties Cavan and Monaghan. The areas combined comprise 16% of the country's population; just over 29,000 women were invited for screening. An analysis of the demographic and socioeconomic features of the target population reveals that it represents the total population remarkably well. Participants were invited from a population register to attend one of two screening units. Follow-up treatment for those with abnormalities takes place predominantly at the Mater Hospital where the facilities of the Departments of Pathology, Surgery and Oncology have been made available to the programme. Almost 18,000 women had a mammogram in the first round of screening, an overall response rate of 62%. A total of 129 cancers were detected, a prevalence of breast cancer of 7.2 per 1,000. Of those, 15 (11.6%) were entirely intraduct, and an additional 7 (5.4%) had minimal invasion. This is considerably higher than the proportion of intraduct cancers seen in referral practice populations.

Prospective evaluation of a composite scoring system for mammographically detected cytologically assessed impalpable breast abnormalities.

The aim of all breast screening programmes is a reduction in deaths from the disease. It is hoped that this can be achieved with minimal intervention in the patient cohort who do not have cancer. In this study we have assessed the efficacy of a combination of mammographic and cytological scoring systems in the evaluation of 208 women with screen-detected non-palpable breast lesions. All mammograms were scored 1-5 and those with a score of 3 or more required needle localization. A cytology score of 1 to 5 was generated for each patient according to a similar system and an aggregate score for each patient was achieved by the addition of the mammographic and cytology score. Ninety-three of the 208 patients had malignancy--the positive predictive value for mammography alone in this series was 45%. All 58 patients who had an aggregate score of 8 or greater had cancer. The 60 patients who had an aggregate score of 4 had benign disease on excision biopsy. We suggest that a 'wait and repeat mammogram' approach is appropriate in patients with grade 3 mammography and benign (grade 1) cytology. Patients with an intermediate aggregate score of 5-7 should have an excision biopsy and those with an aggregate score of 8 could have definitive surgery rather than excision biopsy. Application of this aggregate scoring technique would enhance the delivery of more appropriate surgery to a majority of patients with screen-detected breast abnormalities.

Enhanced in vitro growth suppression of human glioblastoma cultures treated with the combination of recombinant fibroblast and immune interferons.

In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.

Operative assessment of intestinal viability.

Acute intestinal ischemia and infarction remain serious clinical problems despite early operative intervention. Accurate intraoperative assessment of intestinal viability is essential in determining the limits of resection in patients with intestinal infarction. Clinical features of bowel viability such as color and peristalsis do not correlate uniformly with bowel survival, and as a result, several techniques have been developed to assess intestinal blood flow at the time of operation. The requirements of an ideal viability test are: 1. The technique must have ready availability, preferably in every operating theater dealing with abdominal emergencies. 2. The necessary equipment must not be cumbersome or require specialized personnel. 3. The method must be accurate with a minimum of false-negative results and, more importantly, few false positives. A false-negative results leaves in situ nonviable bowel, which may lead to early perforation and late stricturing. This situation may be recoverable with further surgical intervention, however. On the other hand, a false-positive assessment of bowel viability results in the resection of potentially recoverable intestine, which is lost forever and may represent a vital difference for morbidity-mortality and long-term nutrition. 4. The technique must be objective and be reproducible. 5. The method must be cost effective. To date, only two tests have found widespread acceptance and clinical applicability: fluorescein assessment and Doppler studies either with ultrasound or as refined in laser velocimetry. Although other techniques may be of some value today or in the future, the most practical approach would appear to be to use fluorescein assessment under a modified Wood's lamp as the initial method of evaluating intestinal viability and either Doppler ultrasound or perfusion fluorometry for any areas of particularly doubtful viability.

Minimally invasive parathyroidectomy with operative ultrasound localization of the adenoma.

BACKGROUND: Minimally invasive parathyroidectomy is the procedure of choice for primary hyperparathyroidism due to parathyroid adenoma. Adequate perioperative adenoma localization is essential for this operation. We describe a technique using ultrasound to perform minimally invasive parathyroidectomy. METHODS: 99mTc sestamibi scanning was performed on patients with primary hyperparathyroidism to localize parathyroid adenomas; no intraoperative gamma probe was used. We also performed pre- and intraoperative ultrasound scanning to localize these adenomas. RESULTS: All patients underwent successful localization and removal of their parathyroid adenomas. At follow-up, all patients were well, with calcium within normal limits. CONCLUSION: The use of intraoperative ultrasound facilitates minimally invasive parathyroidectomy and may obviate the need for intraoperative 99mTc sestamibi scanning.

Comparison of oestrogen receptor assessment in frozen and paraffin sections.

Estimation of oestrogen receptors (ER) in breast carcinoma has important therapeutic and prognostic implications. The dextran-coated charcoal (DCC) biochemical technique is being replaced in many institutions by immunohistochemical techniques. The aim of this study was to assess the level of agreement between ER counts in frozen and paraffin sections. Ninety-seven infiltrating breast carcinomas were studied immunohistochemically, for ER in frozen and paraffin sections. Cases were classified as ER-positive if > or = 10% of the tumor cells were positive. Both techniques gave a high level of correlation and agreement. There was complete agreement in classifying cases as ER-positive or ER-negative. ER estimation on only one case was outside 2SD of complete agreement. Oestrogen-receptor content can be assayed satisfactorily in paraffin sections and offers many advantages over the frozen section technique.

Prognostic factors in extensive mesenteric ischaemia.

The records of 65 patients with diagnoses of extensive intestinal ischaemia during the 10 years from December 1973 to January 1984 were retrieved from 18 hospitals in Ireland. There were 32 males and 33 females, ranging in age from 20 to 96 years (mean 69.8 years). Duration of symptoms ranged from 4 h to 8 days. Pain was the most common presenting feature. Gastrointestinal haemorrhage was apparent in 31%, hypotension in 28% and atrial fibrillation in 43%. Associated vascular disease was present in 43%. There were elevations of serum inorganic phosphate in 15%, leucoytosis in 65% and metabolic acidosis in 67%. The mean interval from hospital admission to operation in survivors was 14.5 h, whereas the mean delay in those who died was 44 h. The correct preoperative diagnosis was made in 23 (35%) and the aetiology of intestinal ischaemia was recorded as: thrombosis 25 (39%), embolism 12 (18%), adhesions/volvulus 4 (6%) and indeterminate in 24 (37%). Laparotomy was performed in 49: gangrenous bowel was resected in 29 and six had operations designed to revascularise the intestine. The remaining 14 patients either had laparotomy alone (12) or an inappropriate operation (2). In 46 patients (70.8%) who died, death was related to three factors: the mean age of survivors was 7 years less than that of patients who died, the interval to laparotomy was on average 30 h less, and the length of ischaemic bowel was on average 61% less.

Early post-splenectomy sepsis after missile injury in adults.

Early septic complications were studied in 292 patients operated on for penetrating missile injury of the abdomen with involvement of either the spleen or the liver, at Basrah Teaching Hospital between January 1983 and April 1986. Depending on associated injuries, patients with splenectomy were divided into three groups, the first with isolated splenic injury, the second with splenic and associated extra-intestinal organ injury, and the third with splenic and intestinal injuries with or without extra-intestinal organ injury. Patients with hepatic injury were classified similarly. Splenectomy was carried out for any degree of splenic injury. Grade I hepatic injuries were managed by débridement and suturing while major grades II-IV underwent segmentectomy or lobectomy. Patients were considered septic if they had any three of four clinical criteria: temperature higher than 39 degrees C; significant haemodynamic deterioration; respiratory alkalosis, or oliguria. Of the total, 79 were excluded due to: early transfer 51, incomplete records 8, perioperative death 11, and having combined splenic and hepatic injuries 9 (excluded by definition), leaving 104 (74.8%) patients with splenectomy and 109 (71.1%) with hepatic injury available for study. Sepsis developed in 48 (46.1%) of patients after splenectomy and in 28 (25.7%) with hepatic injury. This difference was significant (P greater than 0.005). In patients with isolated splenic injury, eight (25.8%) were septic while three (13.6%) of those with isolated hepatic injury developed sepsis. This was not significant (P = 0.32, Fisher's exact test). When either was associated with an injury to an extra-intestinal organ, 15 (50%) of the splenectomy group developed sepsis compared to five (23.8%) of the hepatic injury group. This did not reach significance. When either was associated with intestinal injury, sepsis developed in 25 (58.1%) of the splenectomy patients, in contrast to 20 (30.3%) of patients with hepatic injury. This was significant (P < 0.005). Gram-negative coliforms were the most common organisms isolated comprising 72.5% and 67.8%, in contrast to pneumococci isolated in 5.9% and 3.6% in the splenectomy group and hepatic injury group, respectively.In conclusion, in patients with penetrating missile injuries of the abdomen, the risk of sepsis is increased after splenectomy compared to hepatic injury, only if there was associated bowel injury. This was reflected in the type of causative organism (predominantly enteric flora) despite 'appropriate'antibiotic cover, as well as a fivefold increase in mortality among the splenectomy group. We suggest that splenic salvage, where feasible, is mandatory if associated with intestinal injury.

The value of water-soluble contrast radiology in the management of acute small bowel obstruction.

A series of 127 consecutive patients with symptoms and signs and radiological features suggestive of acute small bowel obstruction underwent water-soluble contrast small bowel follow-through examination. A dose of 100 ml of Gastrograffin in adults, or 20-50 ml in children, was injected via a nasogastric tube and supine plain abdominal radiographs were taken at 30 min and 4 h after administration. If contrast passed to the colon a non-operative course was followed. If there was a clear cut-off in contrast level in the small bowel or if contrast failed to pass into the large bowel by 4 h, patients underwent laparotomy. Based on these radiological findings 15 patients (11.8%) underwent surgery and all had established small bowel obstruction at laparotomy. The remaining 112 patients were successfully managed conservatively. Water-soluble contrast radiology is safe, easy to use and to interpret, and is a major benefit in differentiating mechanical from other causes of small bowel obstruction. Our experience indicates that this underused technique is of significant value in identifying those patients who require urgent surgery.

Gastrointestinal complications after cardiac surgery.

Gastrointestinal complications after cardiac surgery are uncommon, but are associated with a high morbidity and mortality. Over 11 years 8559 procedures requiring cardiopulmonary bypass were performed in this unit and 35 patients were identified who developed gastrointestinal complications after surgery, an incidence of 0.41%. There were nine deaths in this group, a mortality of 25.7% compared with an overall mortality after cardiac surgery in Ireland ranging from 3.24% to 4.81%. These complications required surgery in 21 patients. The most common indication for surgical intervention was upper gastrointestinal bleeding in 10 patients, three patients had acute pancreatitis, two patients had perforated peptic ulcer; two patients had intestinal ischaemia, with five cases of colon pathology. The difficulties of making an early diagnosis are outlined and a low threshold to exploratory laparotomy is recommended.

The prognostic value of nucleolar organiser regions in colorectal cancer: a 5-year follow-up study.

Nucleolar organiser regions (AgNORs) are loops of ribosomal DNA which reflect the cellular activity or malignant potential of the cell and are identified by a specific staining technique. The purpose of this study was to assess the prognostic value of AgNORs in colorectal cancer and to compare it with other accepted prognostic methods. We studied 164 patients who were surgically staged for colorectal cancer and who had complete follow-up data available for 5 years. Using a highly specific silver staining and counting technique each patient was given an AgNOR score. There were 5 Dukes' C tumours, 108 were Dukes' B and 5 were Dukes' A. No cancer deaths occurred in patients with Dukes' A tumours. The incidence of well-differentiated, moderately-differentiated and poorly-differentiated tumours was 37.2%, 53.7% and 9.1%, respectively. Non-survivors had significantly higher AgNOR scores compared with survivors (mean value +/- SD, 14.2 +/- 0.9 vs 8.2 +/- 0.6, P less than 0.0001). In a regression analysis model AgNOR score was the most significant individual variable for predicting survival (chi 2 = 15, P less than 0.01) when compared with Dukes' classification, histological grade, tumour depth or vascular invasion.

Prediction of intestinal recovery after ischaemic injury due to arterial, venous and mixed arterial and venous occlusions.

Methods to predict intestinal viability after release of vascular occlusion were evaluated in a rat model of reversible segmental strangulation. Visual criteria of colour, pulsation and peristalsis in the ischaemic intestine were applied both in the immmediate period after restoration of the circulation and at `second-look' 24 hours later. In addition two simple tests using a Doppler probe and surface fluorescence were evaluated. As a test in identifying nonviable intestine the fluorescent method had an overall sensitivity of 96% with a specificity of 95% for all types of vascular occlusion, which compared favourably with the other methods tested.

The diagnosis and management of splenic artery aneurysms.

The presentation and course of 7 patients with splenic artery aneurysms is reviewed. Three presented with abdominal pain, 2 with collapse and rupture and in 2 it was an incidental finding. Four patients had elective ligation-excision of the aneurysm with splenectomy as had one patient operated on as an emergency, with no operative mortality. The aneurysm size ranged from 20 to 45 mm (mean 30 mm) and histology confirmed atheroma. One patient was managed as a myocardial infarct for 8 hours after admission and a ruptured splenic aneurysm was diagnosed at autopsy, an overall mortality of 14%. A 66-year-old woman in poor general health was managed expectantly and was asymptomatic when lost to follow-up after 2 years.

Pulse oximetry in the diagnosis of non-critical peripheral vascular insufficiency.

Pulse oximetry was used to detect return of pulsatile flow in 27 subjects during reactive hyperaemia following 3 min of total limb ischaemia induced by above knee tourniquet occlusion. Fourteen patients with exercise induced leg pain had 18 symptomatic limbs tested. Thirteen controls had 25 limbs tested. Return of pulsatile flow during reactive hyperaemia occurred within 20 s of tourniquet release in the 25 control limbs which was then regarded as normal. The mean time for return of pulsatile flow in 18 symptomatic limbs was 53 +/- 37 s (P < 0.05 versus controls). Three limbs had a normal value, two of which did not have peripheral vascular disease. Pulse oximetry correctly identified all 25 asymptomatic limbs and 15 of 16 patients with claudication secondary to peripheral vascular disease (PVD). This modification of the reactive hyperaemia test using the pulse oximeter is simple and quick to perform. It has potential as a non-invasive screening test for PVD, suitable for outpatient assessment.

Laparoscopic-assisted and hand-access laparoscopic surgery.

Therapeutic laparoscopy has developed rapidly since the first report of laparoscopic cholecystectomy in 1986. Several other reports followed before the end of that decade. Recent developments have resulted from a combination of the many technical improvements in laparoscopic equipment, together with the innovation and increasing experience of those performing laparoscopic surgery. Cholecystectomy, appendectomy, gastric fundoplication, and preperitoneal hernia repair are all now widely practiced and often laparoscopy is the favored approach.