Female pseudohermaphroditism due to a maternal adrenocortical tumor.

A 15-yr-old, apparently male, patient presented with a 2-yr history of gynecomastia and poor genital development. A normally formed, but small, penis with a phallic urethra was present, and testes were impalpable. The karyotype was 46,XX, and at laparotomy a uterus, Fallopian tubes, and ovaries were found, but there was no testicular tissue. The mother had had regular periods ever since menarche at 14 yr. She had complained of hirsutism since the birth of the child, and on examination 15 yr later had marked clitoromegaly. Serum androgens were elevated: testosterone, 4.5 nmol/L (normal, 0.5-3); dehydroepiandrosterone sulfate, 18 mumol/L (normal, 3-12); and androstenedione, 35 nmol/L (normal, 3-8). All failed to suppress with dexamethasone. Abdominal computed tomographic scan revealed a 9 X 6-cm mass in the position of the left adrenal gland. This was removed at laparotomy and found to be an adrenocortical tumor. Postoperatively, the androgens returned to normal. Virilization of a female fetus due to androgens secreted by a maternal adrenal tumor has only been described three times previously, and the presentation has never been delayed so long.

The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing's syndrome.

We have reviewed our experience of adrenalectomy performed as part of the management of 56 patients with ACTH-dependent Cushing's syndrome between 1946 and 1993. Forty-three patients were operated on at our institution. Surgery-related mortality did not occur, but complications developed in 14 (33%); these were minor in 12. Eleven patients (29%) of the 38 for whom long-term follow-up data were available and who did not have a proven ectopic source of ACTH subsequently developed Nelson's syndrome, diagnosed on the basis of clinical pigmentation and markedly elevated ACTH levels that were not normally suppressible with glucocorticoids. The effects of prophylactic pituitary radiotherapy were assessed in 38 patients who underwent adrenalectomy at our institution and 18 who underwent surgery elsewhere. Patients who had received prophylactic radiotherapy were less likely to develop Nelson's syndrome (5 of 20, 25%) compared to those who did not (18 of 36, 50%; P > 0.07), and there was a low incidence of radiotherapy-induced hypopituitarism. We conclude that total adrenalectomy has proved to be a safe and effective operation and still may be indicated in selected patients with ACTH-dependent Cushing's syndrome; because prophylactic pituitary radiotherapy reduces the incidence of subsequent Nelson's syndrome by 50%, it should always be considered in the management of these patients.

Surgical therapy of chronic inflammatory bowel disease in childhood.

The overall impression gained from the experience of the Departments of Paediatric Gastroenterology and Surgery attached to St Bartholomew's Hospital are the enormous benefits that surgery has to confer on the large percentage of children with both Crohn's disease and idiopathic proctocolitis who require it. The surgical procedures described in this chapter have been accompanied by a remarkably low complication rate, dispelling the impression that morbidity in such cases would be high. This must in large measure be due to the fact that the children who come to surgery are in as good a state of nutrition as can be achieved by means of the various forms of enteral and parenteral feeding now available. Anxiety about healing of anastomoses and the development of fistulas after surgery for example, has not been a feature of the surgical care of these patients. The principal benefit of surgery has been a clear demonstration of an improvement in growth velocity in both Crohn's disease and idiopathic proctocolitis patients provided always that surgery is correctly timed. It is the author's experience that maximum benefit is achieved if the bulk of the diseased bowel can be removed. Plainly relief of symptoms such as abdominal pain and diarrhoea has also been rewarding. In many instances second procedures such as restorative proctectomy in idiopathic proctocolitis can be timed to fit in with educational commitments. In Crohn's disease the likelihood of recurrence in adult life is high but these patients are in a fit state to cope with further therapy including surgery should the need arise. From the management point of view the close cooperation between physicians and surgeons at all stages has been crucial, firstly to achieve smooth preparation prior to surgery and satisfactory after care. But of even more importance in the assessment of Crohn's disease is the presence of all clinicians involved in the case in the operating theatre so that the surgical options are fully assessed. This united approach avoids any unnecessary anxiety when, as inevitably happens, recurrence of symptoms due to relapse occurs. The involvement of patients of whatever age, and parents in all the decision making processes from the time of diagnosis has been vital. Early discussion about stomas involving members of the Stomatherapy Department has been invaluable. One final important aspect of the management of these patients is the seamless hand-over of care to an adult combined medical and surgical clinic at an appropriate time, usually at the age of 17 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of absorbable mesh to displace bowel and avoid radiation enteropathy, during therapy of pelvic Ewing's sarcoma.

The use of absorbable polyglactin 910 mesh (Vicryl) is described in a case of Ewing's sarcoma of the pelvis. An operation was performed to hold the small bowel and colon out of the pelvis for a temporary period during which radical radiotherapy was delivered. The mesh allowed the temporary displacement of bowel and obviated bowel radiation morbidity.

Surgery for Crohn's disease in childhood: influence of site of disease and operative procedure on outcome.

Factors influencing outcome after surgery have been studied in 67 children requiring bowel resection or diversion of the faecal stream for Crohn's disease. Patients were divided into four groups on the basis of disease location at time of surgery, and mean follow-up was 4.5 years. All three children with panenteric disease (group 1) have relapsed. Best results were observed in cases with disease confined to the small bowel (group 2) and ileocaecal region (group 3), in whom surgery was followed by sustained remission in six out of seven and 24 out of 30 patients respectively. In the 27 children with colitis (group 4), results were mixed. Six of the seven patients who had staged colonic resections with a primary anastomosis relapsed, as did three out of four patients given a loop ileostomy to divert the faecal flow; in contrast, 15 out of 16 children who had a subtotal colectomy with ileostomy as the primary procedure have remained well, with only minor problems involving the rectal stump. An acceleration in growth velocity was observed during the first year after operation in 89 per cent of 40 children studied. Outcome after surgery for Crohn's disease in childhood depends mainly on disease location, but is influenced by the type of primary operation performed. In addition to symptomatic relief the principal early benefit of surgery is improved growth.

Histological transformation of non-Hodgkin's lymphoma: a prospective study.

Forty-three lymph node biopsies were performed prior to retreatment in 30 unselected patients who had relapsed following chemotherapy for advanced non-Hodgkin's lymphoma of low grade histological type. Eight patients (27%) showed unequivocal evidence of transformation to a high grade variety of lymphoma. These included 4 out of 21 cases originally having had follicular lymphoma and 4 out of 9 cases having had diffuse lymphoma. In 2 further patients with follicular lymphoma, relapse was diagnosed following examination of the bone marrow and in one the tumor had clearly transformed. In 5 of the transformed lymphomas the cell type was predominantly centroblastic, in 2 immunoblastic and in the remaining 2 centrocytic (anaplastic). Five of the 9 cases developing high grade lymphoma have died after a median interval of 5 months from transformation, whereas only 3 of 23 cases showing no change are dead. In 4 patients low grade lymphoma persisted in the bone marrow at the time of nodal transformation. The clinical circumstances at the time of rebiopsy were unhelpful in predicting transformation.

Acceleration of linear growth following intestinal resection for Crohn disease.

Twelve patients with Crohn disease aged from 11.3 to 17.1 years, underwent intestinal resection. Eight were prepubertal or in early puberty and 4 in mid or late puberty. Pre-operative assessment included acceleration and compression barium studies and total colonoscopy. In six patients the surgical indication was failure of medical management and in six intestinal obstruction. All but one were in remission 12 months after surgery. Height velocities in the eight pre and early pubertal patients increased dramatically during 6- and 12-month post operative measurement periods compared with preoperative growth. Height velocities in the mid and late pubertal patients showed much less increase. In selected patients, surgical treatment can induce remission resulting in catch-up growth and sustained growth acceleration. In prepubertal and early pubertal patients surgery is likely to improve final adult height.

Stab injury--the experience of an East London Hospital 1978-1983.

A retrospective review of 201 patients with stab wounds admitted to an East London Hospital over a period of six years was performed. There was no striking increase in the annual incidence of these injuries over the period reviewed. The majority of patients were young males who arrived at the Accident and Emergency Department after 1800 h on a Friday, Saturday, or Sunday and had consumed alcohol prior to admission. There were 47 abdominal injuries (23%), 69 thoracic (34%), 51 limb injuries (25%) and 34 injuries involving the head and neck (17%). Forty patients (20%) had injuries involving more than one site. Abdominal stabbings were managed by a selective approach resulting in 28 laparotomies of which only 2 (7%) were negative. Evisceration of small bowel or omentum was always associated with significant intraperitoneal injury.

Linear growth after colectomy for ulcerative colitis in childhood.

Eighteen children and adolescents, of a total of 90 treated in our unit between 1982 and 1992, underwent colectomy for ulceractive colitis. Six (6.7%) of the 90 patients had short stature, i.e., a height below the 3rd centile, and 8 of the 18 who had surgery had a subnormal height velocity, i.e., below the 25th centile for age at the time of surgery. Surgery was performed for resistance to medical therapy (n = 13) or toxic megacolon (n = 5). Surgery was followed by catch-up growth, i.e., increasing height velocity, in eight subjects and cessation of the trend of diminishing height velocity, but without catch-up growth, in five. In 11 of the subjects who were prepubertal, the median height velocity increased from 3.85 cm/year preoperatively to 7.35 cm/year postoperatively (p < 0.01). One year after surgery, 14 of the 18 patients were either asymptomatic or substantially improved. Surgery therefore led to improved linear growth and a prolonged symptom-free period in most of the children and adolescents with ulcerative colitis undergoing this treatment.

Post-treatment laparotomy in the management of Hodgkin's disease.

Tissues obtained by laparotomy and splenectomy from patients with Hodgkin's disease who had received either supradiaphragmatic irradiation for localised disease or combination chemotherapy for advanced disease were examined histologically. 4 of 19 patients considered to be free of abdominal disease after chemotherapy showed residual active Hodgkin's disease; the spleen was the commonest site showing active disease. 2 patients thought to have intra-abdominal disease showed no histological evidence of active disease in the tissue excised. The finding of residual active abdominal disease in patients considered to be in "clinical" remission indicates that the interpretation of the result of treatment depends on the definition of response. A proportion of "relapses" may, in fact, be patients who never achieve genuine remission of disease, whereas the prognosis for those who do achieve complete remission may be even better than currently accepted, and may even amount to "cure". This study shows that histological changes of lymphoreticular tissue can be defined after treatment and may help in determining more accurately the need for further therapy.

The management of localized, infradiaphragmatic Hodgkin's disease: experience of a rare clinical presentation at St Bartholomew's Hospital.

Between 1969 and 1982, 23 previously untreated patients with Hodgkin's disease (HD) confined to infradiaphragmatic sites were treated at St Bartholomew's Hospital. The distinguishing clinical characteristics of the patient population were a male: female ratio of 20:3. The mean age was 39 years, which was significantly older (P less than 0.05) than the mean age of patients with supradiaphragmatic HD (32 years) referred during the same period. Sixteen patients underwent formal pathological staging while one additional patient underwent a diagnostic laparotomy without splenectomy. The final pre-treatment stages were PS IA: 5; PS IIA: 11; CS IIA: 1; PS IIB: 1; CS IIB 5. Splenic involvement correlated closely with the number of nodal sites involved, being detected in 1/7 patients with one site only compared with 8/9 with more (P less than 0.001). Complete remission (CR) was achieved in 21 (91 per cent) patients: 12/12 following 'inverted Y' radiotherapy (RT) and 9/11 following combination chemotherapy. Twenty patients remain alive and 18 continue without recurrence of HD between 15 months and 12 years. All patients who failed to enter CR or who relapsed had presented with three or more sites of involvement or with constitutional ('B') symptoms. These results confirm the generally good prognosis of this uncommon presentation of HD and also suggest that prognosis is determined by the bulk of disease rather than its precise anatomical localization, provided that appropriate therapy is administered.

Detection of spread of malignant lymphoma to the liver by low field strength magnetic resonance imaging.

The accuracy of spin lattice relaxation time (T1) measurement obtained with a low field strength magnetic resonance imager for the detection of spread of malignant lymphoma to the liver was assessed. The results of histological examination obtained at open liver biopsy were compared with liver T1 values in 27 patients with lymphoma. The normal range for T1 was established by scanning 61 healthy volunteers. Magnetic resonance imaging was highly sensitive in detecting hepatic lymphoma, all seven patients with liver lymphoma proved by biopsy having considerably higher T1 values. Specificity was less good. Five out of 20 patients with no histological evidence of hepatic lymphoma had abnormal T1 values. this level of sensitivity is considerably better than that reported for other imaging methods and contrasts with the results of one previous study using a different magnetic resonance system. Low field strength magnetic resonance imaging may prove to be a useful screening test in patients with lymphoma. The presence of a normal liver T1 seems to be a reliable guide to the absence of hepatic disease.

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy.

Bilateral phaeochromocytomas in von Hippel-Lindau disease: diagnosis by adrenal vein sampling and catecholamine assay.

Three unrelated patients with von Hippel-Lindau disease had phaeochromocytomas diagnosed as a result of screening in their third decade. All had raised 24-h urinary noradrenaline levels and obvious unilateral adrenal tumours on ultrasound scanning and computed tomography. The contralateral adrenal appeared either normal or equivocally abnormal using the same imaging techniques. Radiolabelled meta-iodo-benzylguanidine uptake and enhanced T2-weighted magnetic resonance signals confirmed the ipsilateral lesion, but showed no abnormality in the contralateral adrenal. Nevertheless, venous sampling demonstrated abnormally elevated noradrenaline:adrenaline ratios (normal < 1) in blood draining both adrenals in all three patients. All underwent bilateral adrenalectomy: histological examination confirmed bilateral phaeochromocytomas in all three patients, with the smaller adrenal showing tumours between 3 and 11 mm in diameter. A fourth patient with von Hippel-Lindau disease was also evaluated because of a left 'suprarenal' mass discovered by ultrasound scanning. Urinary and plasma catecholamines were normal. Computed tomography showed a normal right adrenal, with a left para-aortic mass lying superior to the left adrenal. Magnetic resonance scanning showed an enhanced T2 signal from the mass, which also showed positive uptake with radiolabelled mIBG. At operation, a non-secretory left para-aortic paraganglioma was found. Venous sampling suggested that the left adrenal was normal, and this was confirmed on histology. Venous sampling for catecholamine assays is effective in locating small bilateral phaeochromocytomas and defining a normal adrenal gland, and can be useful in preventing unnecessary or repeat operations in patients with non Hippel-Lindau disease.

Posttreatment laparotomy as a guide to management in patients with Hodgkin's disease.

Staging laparotomy and splenectomy were performed on 46 adult patients after combination chemotherapy for advanced Hodgkin's disease (HD). There was no preoperative evidence of intra-abdominal disease in 32 patients, 27 of whom were in complete clinical remission, while five had only residual mediastinal abnormalities. In the remaining 14 patients, there was clinical suspicion of active HD. Histologically abnormal tissue was obtained from 19 of 46 (41%) operations. Active abdominal HD was detected in six of 46 patients (13%) or in six of 19 patients having previous evidence of intra-abdominal disease (31%). The spleen was involved in all patients, and in two of these patients there was evidence of both active and ablated disease. Pathologic evidence of ablated HD was detected in 13 patients. The prediction of active intra-abdominal HD, by lymphography or by computerized tomographic scanning, following mustine, vinblastine, procarbazine, and prednisolone therapy, was frequently inaccurate. There was no operative mortality. Morbidity was similar to that of pretreatment laparotomy. At a median followup of 26.5 months (range 5-59), 39 of 40 patients with no evidence of active abdominal HD remain in continuous remission. The contribution of posttreatment laparotomy toward the management of patients with HD is discussed.