Primary necrotizing fasciitis of the breast: a case report and review of the literature.

Primary necrotizing fasciitis of the breast is extremely rare. We describe a case of a 51-year-old diabetic smoker who presented with primary necrotizing fasciitis of the breast, with signs of severe systemic sepsis. She required intravenous antibiotics, radical emergency surgery, intensive care treatment and inotropic support. After daily wound inspections and changes of dressings, the wound was amenable to delayed primary closure on day 6. We describe this case in detail and review the literature on this extremely rare, but potentially fatal, infection.

Recurrent appendicitis.

BACKGROUND: The existence of appendiceal inflammation which resolves spontaneously without surgical intervention has long been controversial. This study was undertaken, therefore, to determine the existence and incidence of recurrent appendicitis. METHODS: The existence of a large database of patients with abdominal pain enabled a retrospective study of the casenotes of the 1084 patients who had an inflammed appendix removed between January 1982 and December 1991 in a Scottish District General Hospital. Sixty consecutive patients who had a normal appendix removed during this period were also studied. RESULTS: Seventy-one patients (6.5 per cent) attended the accident and emergency department 89 times with symptoms and signs compatible with appendicitis which resolved spontaneously between 3 weeks and 12 years before an attendance during which an inflamed appendix was removed. There were significant differences in clinical signs and symptoms (using the Alvarado scoring system) between patients whose symptoms resolved, those with a normal and those with an inflamed appendix. Those who had a normal appendix removed were more likely to be female than those with resolving symptoms (67 versus 42 per cent, P < 0.01). CONCLUSION: Recurrent appendicitis exists and affects at least 6.5 per cent of those who ultimately have an inflamed appendix removed.

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.

Treatment of sulphasalazine-induced agranulocytosis with granulocyte macrophage-colony stimulating factor.

Sulphasalazine-induced agranulocytosis is a rare but potentially life threatening complication. A variable mortality rate has been reported, from 6% to 20%, and is related to the duration of neutropenia. Previous case reports have shown that the use of granulocyte macrophage-colony stimulating factor (GM-CSF) in treating drug-induced agranulocytosis may shorten the period of neutropenia and hence lead to improved survival. It may also be a less costly treatment option that supportive care alone due to reduction of hospital stay as a consequence of a shortened duration of neutropenia. We report a case in which sulphasalazine had been used in the treatment of ulcerative colitis and the subsequent agranulocytosis was treated successfully with GM-CSF, something which has hitherto been unreported.

Restoration of intestinal continuity following Hartmann's procedure: the Lothian experience 1987-1992.

Restoration of intestinal continuity following Hartmann's procedure is associated with high morbidity (anastomotic leak rates 4-16 per cent) and mortality (0-4 per cent) rates. A total of 178 patients, under the care of seven different surgical units, underwent reversal of Hartmann's procedure during a 5-year period, representing the largest series yet reported. The mortality rate of the study group was 0.6 per cent, the anastomotic leak rate was 3.9 per cent and the incidence of anastomotic stricture was 6.7 per cent. The median time interval between resection and reversal was 92 days and no relation was found between timing and complications. Anastomotic stricture occurred significantly more commonly in stapled than in sutured anastomoses (P < 0.05); however, leaks were equally common in both types. The mean age of the patients who developed major complications was not statistically different from that of the rest of the study group and there was no difference in premorbid state. The authors believe that the low complication rates reported in this series may be attributable to the high level of operator experience in performing this technically difficult procedure, which was done by a consultant in 66 per cent of cases and by a senior registrar in 33 per cent.

Intravenous cholangiography in preoperative assessment of patients considered for laparoscopic cholecystectomy.

This study examines the role of intravenous cholangiography in the preoperative assessment of the first 100 patients considered for laparoscopic cholecystectomy at this institution. Intravenous cholangiography detected common bile duct (CBD) stones in 10 patients, of whom only five had a dilated CBD (> 8 mm). There were no cases of inadequate visualization of the CBD using IVC and no allergic reactions to the contrast medium. All CBD stones were confirmed by either endoscopic retrograde cholangiopancreatography (ERCP) or exploration of the CBD. There have been no cases of missed CBD stones during a follow-up period of 8 to 18 months. In contrast, ultrasound scanning was only able to detect one CBD stone, and there was a 14% incidence of inadequate visualisation of the CBD. Intravenous cholangiography is a safe, inexpensive, and highly accurate technique for assessing the CBD in patients undergoing laparoscopic cholecystectomy, with false-positive and false-negative rates of 0 in this study. The timing of the investigation permits preoperative clearance of the duct by ERCP and, should this fail, the option of a single procedure of open exploration of the CBD.

Open biliary surgery and the use of routine inpatient audit.

'Morbidity profiles' offer a practicable and effective method of assessing overall surgical performance. In this study they have been used to document the results of elective and emergency open biliary surgery carried out on 246 consecutive patients over a 2-year period. The results demonstrate that such surgery for the treatment of cholelithiasis and its complications is extremely safe. There was one postoperative death (0.4%) and an in-hospital major morbidity rate of 4.6%. Minor morbidity was common, especially in the elderly and following emergency surgery. The data presented here will be of particular interest to the increasing number of surgeons advocating laparoscopic biliary surgery.

Rectal examination in patients with pain in the right lower quadrant of the abdomen.

OBJECTIVE: To determine whether rectal examination provides any diagnostic information in patients admitted to hospital with pain in the right lower quadrant of the abdomen. DESIGN: Casualty officer or surgical registrar recorded symptoms and signs on admission on detailed forms. Final diagnosis was noted on discharge from hospital. SETTING: District general hospital. PATIENTS: 1204 Consecutive patients admitted to hospital with pain in the right lower quadrant of the abdomen as their major complaint; 1028 had a rectal examination on admission. MAIN OUTCOME MEASURES: Odds ratio for each symptom and sign related to final diagnosis. Results of multiple logistic regression analysis for acute appendicitis. RESULTS: Right sided rectal tenderness, present in 309 of those examined, was more common in patients with acute appendicitis (odds ratio 1.34, p less than 0.05). This odds ratio was considerably less than that for other clinical signs--namely, tenderness in the right lower quadrant (odds ratio 5.09), rebound tenderness (3.34), guarding (3.07), and muscular rigidity in the abdomen (5.03). In the logistic regression analysis of patients with acute appendicitis, when allowance was made for the presence or absence of rebound tenderness, rectal tenderness on the right lost its significance. Six patients had masses palpable rectally, of which three were palpable on abdominal examination; the other three patients had acute appendicitis. No other unexpected diagnoses were established, and no useful additional diagnostic information was obtained by routine rectal examination. CONCLUSION: If patients presenting with pain in the right lower quadrant of the abdomen are tested for rebound tenderness then rectal examination does not give any further diagnostic information.

Postanal repair: which patients derive most benefit?

Forty-two patients (37 women, 5 men; mean age 61 years) with varying degrees of anal sphincter dysfunction were treated by postanal repair. Results were analysed in relation to age, sex, presenting complaint and the results of preoperative anorectal physiological tests. Complete continence was restored in 13 (31%), while acceptable but slightly impaired control was achieved in a further 17 (40%). Twelve patients (29%) remained or became totally incontinent. The likelihood of a successful outcome was greater in those presenting with complete incontinence (77% improved) than in those retaining control of solid stool (29% improved, 29% unchanged, 43% worse). Age and sex had no effect on results but pudendal neuropathy, identified in 74% overall, slightly reduced the chance of success. In nine postoperative patients studied, neither the anorectal angle nor anal canal length bore any relation to the results of surgery.

Measurement of sialyl-transferase activity in isolated colonic mucosal cells of the rat.

An assay for sialyl-transferase activity in isolated rat colonic mucosal cells has been developed. Total and specific activity with asialobovine sub-mandibular gland glycoprotein and endogenous substrates was approximately two-fold higher in the proximal, relative to the distal, colon. These activities were similar when asialo-alpha-acid glycoprotein was used as substrate. Endogenous activity was approximately 10-fold lower than with exogenous substrates in both proximal and distal colonic segments. Analysis of total and specific sialyl-transferase activity up to 7 weeks after jejunoileal bypass (JIB) and sham operation showed a marked increase at the first week, decreasing toward normal by week 7. Similar differences between proximal and distal colon, and with the type of substrate, were found with both groups of operated animals. Histochemical analysis showed small elevation after 1 week for sialo and sulphomucins after the JIB operation only.

Effect of hypothermia on intestinal adaptation and carcinogenesis in the rat.

Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a 6-week course of azoxymethane (total dose 90 mg kg-1). The second group (n = 7) acted as hypothermic controls. Another 2 groups maintained at 22 degrees C received azoxymethane (n = 15) or served as normothermic controls (n = 15). Overall food intake was 42% higher in the hypothermic groups, yet at sacrifice mean body weight was 13% lower (P less than 0.01). Hypothermia and azoxymethane combined to produce the following increases in crypt cell production rate (CCPR), as determined stathmokinetically: duodenum 170%, jejunum 172%, ileum 74%, proximal colon 227% (P = 0.05-0.01). Independently hypothermia had no effect, but azoxymethane produced 76-156% increases in CCPR throughout the large intestine. Although hypothermia did not affect overall tumour yield, the mean diameter of proximal colonic tumours was increased by 65% (P less than 0.05). In rats receiving azoxymethane, hypothermia stimulates cell proliferation in the small bowel as well as in the proximal colon, where it has a correspondingly mild cocarcinogenic effect.

The tropic effect of intrarectal deoxycholate on rat colorectum is unaffected by oral metronidazole.

Intrarectal administration of sodium deoxycholate (SDC) enhances experimental colorectal carcinogenesis, an effect that is partly vitiated by oral metronidazole. The effect of topical SDC with or without concurrent metronidazole on colorectal cell proliferation was explored in male Sprague-Dawley rats (n = 30) allocated to five groups. Two groups received thrice weekly intrarectal instillations of 1 ml N saline or 1 ml 0.12 M SDC. A third group received SDC plus metronidazole 22.5 mg/kg/day in the drinking water. Controls had no instillations or metronidazole alone. At time of killing (10 weeks), crypt cell production rate (CCPR) was determined by the stathmokinetic technique for four large-bowel segments. Saline had no significant effect on colorectal CCPR but SDC produced increases throughout, varying from 53% in the proximal colon to 222% in the rectum (P less than 0.01). Metronidazole did not reduce this effect, although given alone it reduced colonic CCPR by 40 to 50%. The direct tropic effect of bile acids could largely explain their cocarcinogenic properties. Since metronidazole does not prevent this increase in cell proliferation, its mildly protective role against cancer may reflect the presence of fewer anaerobes capable of degrading bile acids to carcinogenic metabolites.

Bile acids in experimental colorectal cancer.

Cogent epidemiological and experimental data implicate bile acids as endogenous co-carcinogens in colorectal cancer. A series of experiments was designed to test the ability of sodium deoxycholate (SDC) to promote intestinal hyperplasia and neoplasia in rats (n = 265). The intermediary role of faecal anaerobes was explored in animals receiving oral metronidazole. Intrarectal instillation of SDC trebled tumour yield in functioning large bowel and increased both crypt depth and crypt cell production rate. Metronidazole reduced this tumour promotion without affecting SDC-induced hyperplasia. By contrast, SDC was totally inactive in colon isolated as a Thiry-Vella fistula. Bile acids probably promote colorectal carcinogenesis by stimulating mucosal hyperplasia but only in the presence of faeces.

Distal transposition of rat caecum does not render it susceptible to carcinogenesis.

As the relative resistance of rat caecum to chemical carcinogens could reflect its luminal environment, caecal mucosa was exposed to the distal faecal stream in male Sprague-Dawley rats (n = 50) previously treated with azoxymethane (total dose 90 mg/kg sc). After colonic transection at the pelvic brim, the caecum was inserted isoperistaltically between colocaecal and caecorectal anastomoses (n = 30); an ileocolic anastomosis restored intestinal continuity. Controls (n = 20) had transection and reanastomosis at equivalent points of the bowel, plus caecotomy and resuture. Caecal crypt cell production rate, as determined stathmokinetically at 28 weeks, was not consistently affected by transposition. No tumors developed in either transposed or orthotopic caecum, apart from three suture-line tumours found at the caecotomy site in controls. The colonic tumour yield in controls (1.4 +/- 0.3 per rat : mean +/- SEM) matched that after transposition (1.5 +/- 0.2), but anastomotic tumours were twice as common after transposition (p less than 0.05) and rectal tumours were increased four-fold (p less than 0.05). The caecum remains resistant to carcinogenesis despite transposition to a distal colonic environment. Local epithelial defence mechanisms are more important than luminal contents in maintaining this resistance.

Rat colonic mucosal cell sialic acid metabolism in azoxymethane-induced tumours.

Colonic tissue was examined from normal (control) rats and azoxymethane- (carcinogen-) treated animals. Tumour-bearing colons from azoxymethane-treated rats were divided into malignant and non-malignant areas. Mucosal cells were prepared from the three types of colonic tissue and then examined for DNA and protein content and for the activities of ten enzymes involved in sialic acid metabolism. Enzyme activities were related to either the protein or the DNA content of fractions. The DNA content of cell homogenates was significantly different between tumour and non-malignant tissue and between both these tissues and normal mucosa. The protein content of the 100000 X g membrane pellet and supernatant fraction did not vary significantly between normal and non-malignant material but both these tissues differed significantly from tumour tissue. Significant variation between normal control and tumour tissue was detected at all levels of sialic acid metabolism, including N-acetylhexosamine interconversion and phosphorylation, sialic acid formation and activation, CMP-NeuAc breakdown and transfer and sialic acid release from glycoconjugates. The results indicate that major changes at all levels of sialic acid metabolism are associated with malignancy in rat colonic mucosa. Some of these changes are apparent in non-malignant mucosa and may reflect a pre-malignant state.