Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome.

BACKGROUND/PURPOSE: Although medullary thyroid carcinoma (MTC) can occur sporadically, in the pediatric population it is most often associated with the multiple endocrine neoplasia syndrome (MEN type 2). Traditional screening was based on evaluation of basal and stimulated serum calcitonin levels. The recent cloning of the MEN2 gene on the RET proto-oncogene of chromosome 10 now allows for testing of gene carrier status in individuals at risk who could benefit from prophylactic treatment. The current study was undertaken to determine the appropriate age for safe total prophylactic thyroidectomy. METHODS: Over a 16-year period, 12 patients with a family history of MEN2A and one with a MEN2B underwent total thyroidectomy and central neck dissection without parathyroid autotransplantation. Four patients (31%) were treated previously for Hirschsprung's disease. RESULTS: In seven patients (mean age, 11.8 years) undergoing biochemical screening for diagnosis, multifocal MTC and C cell hyperplasia (CCH) were found in all the resected specimens. Of six patients identified with genetic screening (mean age, 9.1 years), two had elevated stimulated calcitonin levels, one (age 14) had evidence of MTC, and one (age 6) had CCH. Four patients with normal calcitonin levels had no evidence of MTC (ages 6, 8, 10) but there was one occurrence of CCH (age 11). No permanent postoperative hypoparathyroidism or recurrent laryngeal nerve damage occurred in this series. With a mean follow-up of 4 years (range, 1 to 14 years), the overall disease-free survival is 100%. CONCLUSIONS: From this study the authors conclude that total thyroidectomy can be performed safely in children and should be the treatment of choice in patients with a family history of MEN2A carrying a germinal RET mutation even if the serum basal or stimulated serum calcitonin level is normal. Total thyroidectomy should be performed as early as 5 years of age before the occurrence of CCH or MTC.

The PMAC code of marketing practices: time for improvement? Pharmaceutical Manufacturers Association of Canada.

In this issue (see pages 351 to 356) Dr. Joel Lexchin proposes reforms that could help the Pharmaceutical Manufacturers Association of Canada (PMAC) adapt its Code of Marketing Practices to changing times. The PMAC code reflects the ethical concerns of drug manufacturers and speaks to the need for high standards in promotional activities. The code is a commendable beginning, but it does not go far enough in ensuring ethical practice. The PMAC should take this opportunity to address the concerns raised by Lexchin. For example, proactive assessment of advertising would improve the current system.

[Surgical treatment of thyroid diseases in children]. / Le traitement chirurgical des pathologies thyroïdiennes chez l'enfant.

UNLABELLED: In order to review the experience of a single institution with thyroid surgery and identify prognostic factors, we did a retrospective chart review of all patients who underwent thyroid surgery between 1980 and 1995. Fifty patients, 32 girls and 18 boys, underwent thyroid surgery. Clinical presentation include a thyroid nodule (36 patients), a family history of MEN syndrome with a positive pentagastrin stimulation test (10), diffuse nodular goitre (3) and a neonatal cervical mass (1). Radiologic investigation include ultrasonography in 58% of cases, radionucleide imaging in 70% of cases. The mean age at surgery was 13.3 years and the delay between onset of symptoms and diagnostic was 13 months. Twenty-one patients had a lobectomy +/- isthmectomy, 19 had a total thyroidectomy and 10 had a subtotal thyroidectomy. Nine patients required a second surgery to complete the surgical treatment, and perform a total or near total thyroidectomy when the final pathology showed a carcinoma. A well differentiated carcinoma was found in 52% of the patients, a medullary carcinoma in 20% and a benign lesion in 28% of cases. Nine patients had local or distant metastases at initial surgery. Post-op treatment consisted of suppressive hormonotherapy in all cases of cancer and radioactive iodine when recurrence occurred in 24% of patients and when metastasis where present. Survival remained at 100%. CONCLUSION: Thyroid nodules should be rapidly investigated in children because of a high potential of cancerous lesions. With an aggressive surgical treatment and post-op I131 for recurrent lesions and metastasis the prognostic remains excellent.

Tailgut remnant--or teratoma?

The tailgut is the distalmost portion of the embryonic gut, located caudal to the cloacal membrane. Up to the sixth week of development, it is in close proximity to the distal end of the notochord and the neural tube. It completely regresses by the seventh week, but some caudal duplication-like cysts have been attributed to its remnants. We report a full-term male born with a large heterogeneous sacral mass. Severe bony abnormalities of the coccyx, sacrum and lower lumbar vertebrae were present, but the infant was neurologically intact. At surgery, the upper cystic structures within the mass were found to communicate with the dura, while the solid component, whose surface resembled intestinal mucosal folds, was closely related to the perirectal tissues. The mass was completely resected and the dura oversewn. Since this complex mass contained all three cell lines in an aberrant location, it satisfies the definition of a sacrococcygeal teratoma. However, its unique architecture suggests a malformative, rather than tumoral origin. The macroscopic appearance of this lesion reflects the embryonic relationship between the tailgut, the neural tube and the notochord.

Changes in the presentation of intussusception.

Intussusception is most often diagnosed in well-nourished 7- to 10-month-old infants, but may be overlooked in older children. From 1985 to 1991, we treated 118 boys and 62 girls ranging in age from 2 months to 15 years (average, 22.6 months). Thirty-seven percent were older than 2 years, significantly more than in earlier experience at this institution. Overall, children with intussusception had a less than average weight (P < .05). The majority of intussusceptions in all age groups were idiopathic. Seventy-three percent of the patients were treated successfully by barium enema. The presence of air-fluid levels on the plain radiograph decreased the success rate of barium enema reduction from 81% to 49%. Barium enema reduction should nevertheless be attempted regardless of the age of the patient or the duration of symptoms, and routine surgical exploration is never recommended.

Surgical indications in antenatally diagnosed ovarian cysts.

The antenatal diagnosis of ovarian cysts poses a therapeutic dilemma because the natural history of these lesions is not well known. A retrospective review from 1980 to 1989 showed 29 ovarian cysts in 27 patients diagnosed by prenatal ultrasonography performed between 28 and 36 weeks of gestation. Nineteen cysts were initially observed. Eleven cysts resolved (diameter less than 2 cm), three are decreasing, three were lost to follow-up, and two underwent resection. Eight patients underwent surgical exploration immediately following birth. The diagnosis of benign ovarian cyst was confirmed histologically in all cases. A review of the literature showed an additional 230 cases of antenatally diagnosed ovarian cysts. Simple cysts of the ovary tend to resolve spontaneously and, therefore, may be treated conservatively. Serial ultrasonography allows accurate diagnosis and long-term assessment of ovarian cysts in the neonate and may prevent unnecessary oophorectomy. Patients with cysts larger than 4 cm may be candidates for percutaneous aspiration, or should undergo removal of the cyst because of a significant risk of torsion. Complex cystic masses, symptomatic ovarian cysts, and cysts that do not resolve should be removed.

[The role of therapeutic laparoscopy in the surgical treatment of intra-abdominal testes in children]. / La place de la laparoscopie thérapeutique dans le traitement chirurgical des testicules intra-abdominaux chez l'enfant.

Over a period of four years (September 1986 to September 1990), 32 impalpable testes were found in 24 cryptorchid boys at Sainte-Justine Hospital, Montreal. 11 (34%) of the impalpable testes were intra-abdominal. Of these, 5 testes were hypoplastic and were removed, 3 by a traditional inguinal transperitoneal orchiectomy and 2 by laparoscopy; 2 testicles were brought down by classic orchiopexy whereas two others underwent a Fowler-Stephens procedure. One of these underwent preliminary laparoscopic clipping of the spermatic vessels followed six months later by open surgery to bring the testis down on the vas and deferential artery and its well-developed collateral circulation. One patient underwent a two-stage open orchiopexy and another had unilateral testicular autotransplantation. The literature is reviewed and surgical indications for therapeutic laparoscopy are discussed.

[Transient fever associated with a reduction of intestinal invagination]. / Fièvre transitoire associée à la réduction de l'invagination intestinale.

Intussusception is a common cause of small bowel obstruction in infancy and early childhood. As in other forms of intestinal obstruction, there is stagnation of enteral content and edema of the bowel wall, theoretically facilitating translocation of bacteria. Since 1987, 85 cases of intussusception have been at this institution, of which 24 underwent laparotomy. Twenty (83%) developed a fever of more than 38.0 degrees at a mean of 11 hours postoperatively, lasting for less than 24 hours. Of the 61 cases that were treated by barium enema (a success rate of 72%), a similar fever peak was recorded in 26 (43%). All but who patients were afebrile on admission, and all were afebrile upon discharge. Hospital stay was 1.8 days for non-operated patients two remained afebrile and 2.9 days for those who developed a transient fever (p less than 0.05). We postulate that this temporary rise in temperature following manipulation of intussuscepted bowel is caused by a transient bacteremia or endotoxinemia due to bacterial translocation through the intestinal wall, similar to the process that has been described in other forms of intestinal obstruction. Awareness of this phenomenon could avoid needless fever workups, thereby reducing costs and hospital stay. The concept of bacterial translocation casts a doubt on the infectious theory of idiopathic intussusception, since the presence of infected mesenteric lymph nodes could follow, rather than proceed the intussusception.

A twenty-year experience with thyroid carcinoma in children.

During the past 20 years, 23 patients (7 males, 16 females) were operated on for thyroid carcinoma in our institution. The average age was 13.6 years (range, 22 months to 27 years). Our series includes papillary carcinoma in 11, follicular carcinoma in four, and medullary thyroid carcinoma in eight patients. Follow-up ranged from 8 months to 20.3 years, with an average of 7.5 years for well-differentiated carcinomas and 4.3 years for medullary thyroid carcinomas. All patients are presently alive with no evidence of progressive disease. Patients with papillary and follicular carcinomas underwent partial thyroidectomy; those with medullary carcinoma underwent total thyroidectomy. Serious complications included three permanent hypoparathyroidism and two tracheostomies, all after secondary neck explorations. The overall results observed in our series of patients seem to support the current conservative approach to well-differentiated thyroid carcinoma, reserving total thyroidectomy for medullary cancer of the thyroid. A more aggressive search for familial medullary carcinoma through use of pentagastrin stimulation leads to early detection and more effective therapy.

Blunt pancreatic injuries in children: the role of percutaneous external drainage in the treatment of pancreatic pseudocysts.

During the past 10 years, 26 cases of blunt pancreatic trauma were diagnosed in our institution. In 42.3% (11/26) the accident was bicycle-related. Seventy-three percent of patients were seen within 48 hours of injury. The most frequent clinical presentations included abdominal pain, tenderness and vomiting. Diagnosis of pancreatic injury was suggested by hypermylasemia in most cases. Associated trauma was seen in seven patients (26.9%) and it was intraabdominal in four (15.3%). Computerized tomography (CT) scan is the single most useful radiologic investigation in evaluating pancreatic trauma. Ultrasound, although less accurate than CT scan in determining the severity of the initial injury, is useful in the evaluation and treatment of pancreatic pseudocysts. Pancreatic pseudocysts developed in ten patients. Spontaneous resolution occurred in five (50%). In three patients, percutaneous external drainage (PED) was successful in treating pancreatic pseudocysts without complications or recurrence at 11, 19, and 31 months. PED is a suitable form of treatment in selected cases of pancreatic pseudocysts. Results in children are better than in the adult population, probably due to the absence of primary pancreatic pathology. We believe that PED should be considered the primary therapeutic procedure for traumatic pancreatic collections prior to more invasive surgical treatment, when there is no evidence of pancreatic duct transection on CT scan.

Management of thyroid nodules in children: a 20-year experience.

The medical records and surgical slides of 58 patients with the diagnosis of thyroid nodules (solitary nodule in 50 patients) are reviewed. The most common cause of thyroid nodules in this series is follicular adenoma (27 patients or 46%). A nuclear scan (technetium or radioactive iodine) was performed in 55 patients, of which 40 showed a cold nodule. Twelve of the 40 cold nodules were malignant (30%). However, for solitary nodules the incidence of cancer is 27%. This last figure is significantly greater than the one recently reported by Hung et al (18.5%). Available diagnostic methods are reviewed and the clinical management as derived from our experience is presented.

Pulmonary sequestration.

A review of 41 patients over a 15-year period with a diagnosis of pulmonary sequestration was undertaken. The most common presenting complaint was repeated infections of the sequestrated segment. Two of our patients were symptomatic since the neonatal period. On an average, each patient was admitted three times to the hospital before undergoing surgery. All our patients had abnormal chest x-rays. Two patients had severe purulent infection needing emergency resection of the sequestrated lobe. In our experience, almost all cases of pulmonary sequestration require surgery in the long-term.

Gastrointestinal manifestations of Sipple syndrome in children.

The diagnosis and management of patients with multiple endocrine neoplasia (MEN) type IIA and type IIB are of special challenge to pediatric surgeons. Patients characteristically present early in life with significant intestinal symptoms at a time when the characteristic phenotypic features of MEN IIB are frequently absent. We are reporting 12 patients with MEN type II (9 with type IIA and 3 type IIB or Sipple's syndrome), all of whom presented with gastrointestinal manifestations. All 12 patients had signs and symptoms of bowel obstruction during the neonatal period. An unusual association of Hirschsprung's disease and MEN IIA was noted in our nine patients found among a kindred of 92 individuals. All three patients with Sipple's syndrome (MEN IIB) had severe gastrointestinal symptoms since birth, including recurrent pseudoobstruction. The possibility of MEN type II should be considered in all cases of bowel obstruction in the newborn period. Screening for medullary carcinoma of the thyroid must be carried out from infancy. A detailed family history is very important to avoid unnecessary surgery for bowel obstruction in Sipple's syndrome.

Treatment of hyperthyroidism in children.

Thirty-three children with hyperthyroidism, an uncommon condition in childhood, were treated at the Hôpital Ste-Justine in Montreal during the period 1961 to 1974. Of these, 31 underwent medical treatment initially. Fifteen were cured by medical treatment only; the other 18 had to undergo subtotal thyroidectomy. When these two groups were compared the advantage of surgery in the treatment of this disease was clear. There were no major complications postoperatively. Two children became hypothyroid. The mean follow-up was 5 years and 6 months.

Neurogenic tumors and VIP-induced diarrhea.

The authors report a case of cervical ganglioneuroblastoma associated with intractable watery diarrhea and hypokalemia. The probable physiopathologic mechanism of the diarrhea and its relation to the vasoactive intestinal peptide secretion (VIP) by the tumor are discussed.

[End to side porto-caval shunt in familial type II homozygote hypercholesterolemia (author's transl)]. / L'anastomose porto-cave termino-latérale dans l'hypercholestérolémie familiae de type II homozygote.

Two patients with homozygous type II familial hypercholemia have had significant improvement by end to side porta-caval shunt. Follow-up is respectively 1 and 4 years. When all the other treatment have failed in lowering blood cholesterol and L.D.L. levels, a portal diversion may help to prevent cardio-vascular atherosclerotic complications in the pediatric age.

[Treatment of hyperthyroidism in childhood and adolescence (author's transl)]. / Traitement de l'hyperthyroïdie de l'enfant et de l'adolescent.

33 cases of hyperthyroidism have been treated at "L'Hôpital Sainte-Justine" of Montréal, during the period 1961-1974. Nearly all patients were submitted to medical treatment. 15 were cured with medical treatment only, and 18 had to be submitted to a subtotal thyroidectomy. These two groups are compared and show the clear advantage of surgery in the treatment of this disease. There was no major post-operative complication. Two patients became definitively hypothyroid. The mean follow-up is five years and six months.

The pathogenesis of intestinal atresia.

The records of 28 patients with duodenal and 31 with jejunoileal intestinal atresia or stenosis were studied. Vomiting and abdominal distention were the most prominent symptoms; an unusual colon may be present in jejunal as well as ileal obstruction and is not pathognomonic for ileal obstruction. Intestinal atresia is associated with a high incidence of preterm babies but with a low incidence of intrauterine growth retardation. Fifty-three infants were operated upon; the overall survival rate was 79 per cent. The high percentage of mortality in duodenal obstruction is due to associated malformations. Theories of the pathogenesis of intestinal atresia do not seem to fit current clinical and experimental evidence in all patients. Possibly, different factors play a role in separate situations.