Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Sacral nerve stimulation in faecal incontinence: position statement based on a collective experience.

OBJECTIVE: Since the first paper published by Matzel et al., in 1995, on the efficacy of sacral nerve stimulation (SNS) in patients with faecal incontinence, the indications, the contraindications, the stimulation technique and follow up of implanted patients have changed. The aim of this article was to provide a consensus opinion on the management of patients with faecal incontinence treated with SNS. METHOD: Recommendations were based on a critical review of the literature when available and on expert opinions in areas with insufficient evidence. RESULTS: We have reviewed the indications and contraindications, proposed an algorithm for patient management showing the place of SNS. The temporary test technique, the implantation technique, the patient follow up and the approach in case of treatment failure were discussed. CONCLUSION: We hope not only to provide a guide on patient management to clinical practitioners interested in SNS but also to harmonize our practices.

[A Multiple endocrine neoplasia type-1 observatory in a French-speaking area. A tool from the Endocrine Tumor study Group (GTE)]. / Observatoire francophone des néoplasies endocriniennes multiples de type 1. Un outil du Groupe d'étude des Tumeurs Endocrines (GTE).

Wermer's syndrome or Multiple Endocrine Neoplasia Type-1 (MEN1) is an autosomal dominant inherited disease, related to mutations in MEN1, an approximately 10-kb gene encoding menin, localized on chromosome 11q13. The Endocrine Tumor Group (GTE) has set up a MEN1 observatory of 1001 regularly followed MEN1 cases. This observatory aims at registering and evaluating MEN1 cases in a large cohort. Any new study on a particular unexplored aspect of the disease may be proposed by a physician to the GTE. This article describes the way to diagnose a new MEN1 case and to register it. Procedures for participating in a new study are presented. Some original results are quoted.

[Endoscopic thyroidectomy via median approach with gas insufflation: analysis of the first 100 cases]. / Thyroïdectomie endoscopique par une approche médiane avec insufflation gazeuse: analyse des 100 premiers patients.

OBJECTIVE: To report the initial experience with videoscopic thyroidectomy using a cervical approach with median placement of the optical trocar and gas insufflation. PATIENTS AND METHODS: Retrospective study of the first 100 consecutive patients. RESULTS: Seven isthmectomies, 86 lobectomies, and 7 total thyroidectomies were performed. Parathyroidectomy for hyperparathyroidism was also performed in 3 patients. Mean operative time was 77 minutes. No post-operative subcutaneous emphysema was noted. Conversion to open surgery occurred in 10% of cases but the conversion rate decreased to 2.6% when the harmonic scalpel became available. Post-operative complications included one transient recurrent laryngeal nerve palsy. There were no hematomas and no hypocalcemia. The mean post-operative pain scale was 2.7 (on a visual scale of 1-10). Mean hospital stay was 1.5 days. The cosmetic result was considered excellent. CONCLUSIONS: Endoscopic total thyroidectomy aided by gas insufflation is technically feasible. The harmonic scalpel aids greatly in dissection and hemostasis. It is a valid option in the surgical management of thyroid disease but careful pre-operative selection of patients is mandatory.

The future: surgical advances in MEN1 therapeutic approaches and management strategies.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disorder associated with numerous neuroendocrine tumors (NETs). Recent advances in the management of MEN1 have led to a decrease in mortality due to excess hormones; however, they have also led to an increase in mortality from malignancy, particularly NETs. The main challenges are to localize these tumors, to select those that need therapy because of the risk of aggressive behavior and to select the appropriate therapy associated with minimal morbidity. This must be applied to a hereditary disease with a high risk of recurrence. The overall aim of management in MEN1 is to ensure that the patient remains disease- and symptom-free for as long as possible and maintains a good quality of life. Herein, we review the changes that occurred in the last 20 years in the surgical management of MEN1-associated functional and non-functional pancreatico-duodenal NETs and thymic and bronchial NETs.

[Thoracic kidney: congenital or traumatic origin?]. / Rein thoracique: origine congénitale ou traumatique?

The discovery of a thoracic kidney in adult patients can lead to three diagnoses, yielding different prognoses and treatment. It can either mean traumatic or congenital diaphragmatic hernia, or a congenital ectopic kidney. Intrathoracic herniation of the left kidney trough a left diaphragmatic rupture is an exceptional discovery. We report the case of a 44 year-old man who met with a car accident 20 years ago, and presented abdominal pain. CT-scan showed an intrathoracic herniation of the left kidney trough a left posterior diaphragmatic rupture. Laparoscopic approach in lateral position showed a traumatic hernia of the left costo-diaphragmatic hiatus only containing the left kidney and its pedicle. After reduction of herniated left kidney into the abdomen, the hiatus was closed by non-resorbable prosthetic mesh. Postoperative course was uneventful.

MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d'étude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

Changing referral patterns for surgical treatment of ulcerative colitis.

OBJECTIVE: To determine whether referral patterns for surgical treatment among patients with chronic ulcerative colitis have changed in recent years, especially in view of the introduction of a new operation, the ileal pouch-anal anastomosis (IPAA). MATERIAL AND METHODS: Between January 1976 and December 1986, 981 patients underwent proctocolectomy at Mayo Clinic Rochester. Brooke ileostomy (N = 300), colectomy with ileorectal anastomosis (N = 33), proctocolectomy with Kock pouch (N = 180), or ileal pouch-anal anastomosis (IPAA) (N = 468) was performed. The indications for surgical intervention were categorized as emergent or elective, the latter including intractability, cancer, and cancer prophylaxis. For analysis, the duration from diagnosis of disease to operation, indications for surgical treatment, and types of operation were subdivided into pre-IPAA era (before 1981) and post-IPAA era (from 1981 onward) for the entire group and for distant versus local patients. RESULTS: More continence-preserving operations were done in 1981 and thereafter (76%) than before 1981 (46%). In the later segment of the study period in comparison with before 1981, fewer operations were done for emergent reasons (4% versus 8%) and a greater percentage of operations were done for elective indications, especially intractability (74% versus 61%). With the advent of IPAA in 1981, patients underwent operation sooner after the diagnosis was made (7.4 years versus 8.6 years before 1981). A smaller proportion of patients underwent operation for cancer prophylaxis during 1981 through 1986 (19%), however, than before 1981 (28%). CONCLUSION: Referral patterns for surgical treatment of patients with ulcerative colitis have changed in recent years--patients are being referred for operation sooner, before complications develop that necessitate emergent procedures. Although the changed referral pattern may be due to the availability of IPAA, other factors may also have a role.

Antibiotic prophylaxis in pulmonary surgery. A prospective randomized double-blind trial of flash cefuroxime versus forty-eight-hour cefuroxime.

The aim of this study was to determine whether a 48-hour antibiotic prophylaxis regimen with a second-generation cephalosporin was more efficient than a flash antibiotic prophylaxis regimen in pulmonary operations. All the included patients underwent lung resection. Patients with preoperative infection were excluded. All the patients were given cefuroxime (1.5 gm intravenously) at the time of the anesthetic induction and again 2 hours later. The randomization was done postoperatively: group 1 was given placebo intravenously (n = 102) and group 2 was given cefuroxime intravenously (n = 101), each every 6 hours for 48 hours. The overall rate of infections was 46% in the 48-hour cefuroxime group versus 65% in the flash group (p = 0.005). The difference remained significant even after an adjustment with prognosis variables (p = 0.01). Six empyemas (6%) in the flash group were noted versus one (1%) in the 48-hour group (p = 0.03). From day 3 to day 8 after the operation, chest x-rays films were more often assessed as being normal in the flash group than in the 48-hour group (p = 0.005). On day 3 after operation, white blood cell counts were 13,020 +/- 1,220 elements/mm3 in the flash group versus 11,620 +/- 1,220 elements/mm3 in the 48-hour group (p = 0.03). A 48-hour antibiotic prophylaxis regimen decreases the rate of deep infections and particularly the rate of empyemas.

Primary hyperparathyroidism with normal serum intact parathyroid hormone levels.

To evaluate the features of primary hyperparathyroidism (HPT) with normal serum intact parathyroid hormone (iPTH) levels, we studied 271 consecutive patients undergoing surgery for primary HPT. In 20 patients, serum iPTH levels were within the normal range (10-65 ng/l). In their records, the most common clinical features were fatigue (n=13), polyuria (n=6), renal stone (n=5), and hypertension (n=5). Mean serum calcium and phosphorus were 2.78 and 0.85 mmol/l, respectively: 14 had serum phosphorus within the normal range. Mean serum iPTH was 48.5 ng/l, and was <45 ng/l in nine patients. Cervical ultrasound demonstrated a parathyroid adenoma in nine, and was normal in four. Tc sestamibi parathyroid scintigraphy always demonstrated an adenoma (9/9). In eight patients, normal iPTH values delayed diagnosis. Physicians should be aware of the possibility of HPT in patients with hypercalcaemia, even when serum phosphorus and iPTH levels are within the normal limits. Particularly, HPT cannot be excluded when serum iPTH levels are below the upper part of the normal range. In such cases, cervical imaging, which has the same sensitivity as in other HPT, should be undertaken. These explorations are useful, because many patients are symptomatic and can take advantage of surgery.

Intra-abdominal gastric volvulus. An indication for gastropexy through laparoscopy.

Intra-abdominal gastric volvulus is a chronic or acute condition that may be cured by conventional surgery through laparotomy. We report a case of subacute intra-abdominal volvulus who benefited from a gastropexy through laparoscopy. We show that this technique is feasible, safe and efficient. Technical details are described to perform the procedure easily and rapidly.

[Practical role of ultrasonography and clinical examination for the diagnosis of acute appendicitis. Prospective study]. / Rôle pratique de l'échotomographie et de l'examen clinique dans le diagnostic de l'appendicite aiguë. Etude prospective.

The aim of this 100-patient prospective study was to compare three types of investigations in the diagnosis of acute appendicitis: initial clinical examination, initial appendicular ultrasound examination, and final results of repeated clinical examinations carried out within the first 48 hours. Final results included initial evaluation, obvious clinical results and definitive results from patients under 48 hour observation for uncertain diagnosis. Clinical initial or appendicular ultrasound examinations were poorly contributive to diagnosis (overall accuracy: 76 percent). On the contrary, repeated clinical examinations yielded a 100 percent sensitivity, a 94 percent specificity, a 94 percent positive predictive value, a 97 percent negative predictive value and a 97 p. 100 overall accuracy. No morbidity was noted in observing patients for 48 hours. Unwarranted appendectomies were carried out in 3 percent of cases. Ultrasonography of the appendix seems useful for the differential diagnosis of acute appendicitis.

[Right laparoscopic adrenalectomy]. / Surrénalectomie droite par coelioscopie.

The transperitoneal laparoscopic approach for right adrenalectomy is performed in patients placed in a lateral decubitus position. Four ports are usually needed (2 or 3, 10 mm ports, 1 or 2, 5 mm ports), inserted in the right subcostal area. After liver retraction, the retroperitonéal space is opened close to the liver, exposing the right adrenal gland and the inferior vena cava. The periphrenic fat and the internal side of the gland are dissected close to the right side of the vena cava in order to expose the main adrenal vein. This vein is double clipped. At the inferior pole of the gland, the inferior adrenal artery is ligated with clips. Before removing and extracting the gland, the right side and the upper pole of the gland are dissected last.

[Acute intra-abdominal gastric volvulus in adults. Defect of dorsal mesogastrium fusion]. / Volvulus gastrique intra-abdominal aigu chez l'adulte. Le défaut d'accolement du mésogastre postérieur.

A case of acute intra-abdominal gastric volvulus in an adult patient is presented. It was caused by the absence of dorsal mesogastrium fusion and was responsible for a gastric necrosis and peritonitis. The mobile spleen displaced the greater curvature of the stomach to the right. This case-report illustrates an association between an anatomical abnormality and a case of intra-abdominal gastric volvulus.

[Repair of midline incisional hernias using the Lazaro da Silva aponeuroplasty technique]. / La cure des éventrations médianes selon la technique d'autoplastie de Lazaro da Silva.

STUDY AIM: The aim of this retrospective study was to assess Lazaro da Silva's rectus sheath aponeuroplasty technique for repair of midline incisional hernias situated above the arcuate line. PATIENTS AND METHOD: Twenty-six patients underwent surgical repair of a supraumbilical (n = 19) or periumbilical (n = 7) incisional hernia. Six patients had had repeated laparotomies and two of them had recurrent incisional hernia. There were 11 obese patients (42%). Muscle diastasis ranged from 4 to 20 centimeters (mean: 9.7 cm). Three overlapping aponeurotic and peritoneal layers were used. The peritoneal sac was partially or totally incorporated in the repair. RESULTS: There was one postoperative death at day 5 from acute pancreatitis in a patient with associated cholecystectomy. Postoperative complications occurred in six patients. There were 3 abdominal wall infections. Obesity was the main factor associated with operative complications (p = 0.03). Mean follow-up was 19.1 months. There were 2 recurrences, one of them related to an abdominal wall infection. CONCLUSION: The Lazaro da Silva aponeuroplasty technique compares favourably with alternative techniques using mesh implants. It is indicated for incisional hernias less than 20 centimeters wide, situated above the arcuate line.

[Videoendoscopic approach for parathyroid adenomas: results of a prospective study of 100 patients]. / Exérèse vidéoendoscopique des adénomes parathyroïdiens: résultats à propos d'une série prospective de 100 patients.

STUDY AIM: The aim of this prospective study was to report the results of 100 consecutive video-endoscopic parathyroidectomies in patients suspected of having a single adenoma. PATIENTS AND METHOD: From March 1997 to September 2000, 80 females and 20 males (mean age: 49.5 years) were operated on. They were selected on the basis of the following criteria: preoperative imaging in favour of a single adenoma, absence of goiter and no prior neck dissection. The technique required three trocars; one 5 mm trocar inserted through the middle line of the neck for the 0-degree 5 mm endoscope, and two 3 mm trocars inserted laterally in order to perform a bilateral exploration. The neck was inflated to 10 mm Hg pressure with a low flow (3 L/min). RESULTS: Exploration was unilateral, bilateral and interrupted respectively in 52, 45 and 3% of the cases. The reasons for stopping were: an incidentally discovered thyroid carcinoma; moderate bleeding occurring from an anterior jugular vein after introduction of a lateral trocar; and a too-short neck. Parathyroid abnormalities were found in 86% of the patients (84 single adenomas, one double adenoma, one hyperplasia of the four glands). In 14% of the cases, the exploration was unsuccessful. A horizontal cervicotomy was required in 15% of the cases (14 negative explorations and one hyperplasia of the four glands). No intraoperative or postoperative complications occurred. The mean hospital stay was 24 hours. After 3-month follow-up, the serum calcium level was normal in 96% of the cases and cosmetic results were excellent. CONCLUSION: A video-endoscopic approach for parathyroidectomy is feasible and safe. With sufficient experience, a bilateral and complete exploration of the neck is possible. Therefore this technique represents a good alternative to the traditional cervicotomy in patients with uniglandular disease.

[Specific morbidity of substernal goiters. A comparative study with a matched series of cervical goiters]. / La morbidité spécifique des goitres plongeants. Etude comparative avec une série appariée de goitres cervicaux.

The operative morbidity rates in patients operated for substernal goiter (SG) vary from one series to another. The aim of this study was to reevaluate the morbidity using a matched technique. Each SG was matched to a cervical goiter for surgical technique, histology and thyroid function. There were 97 SG (75% of women), 43% with normal thyroid function, 28% with mild hyperthyroidism, 29% with hyperthyroidism. 87% of thyroidectomies were bilateral. Mean age was 66.5 +/- 11.5 years versus 55.8 +/- 11.9 years for cervical goiters (p < 0.001). The percentage of men was higher for SG than for cervical goiter (25% versus 10%, p < 0.01). Specimen weighed 166 +/- 109g versus 76 +/- 95g (p < 0.0001). Total volume of drainage was 164.0 +/- 68 ml versus 123.2 +/- 68 ml (p = 0.003). No operative death occurred. Early hypoparathyroidism rate was 3% versus 2% (p = 0.5), and late hypoparathyroidism was 1% versus 0% (p = 0.5). There was a 10 mg/l in serum calcium post-operative drop in both groups but no change in serum phosphate was noted (bilateral thyroidectomies). The early recurrent laryngeal nerve palsy rate was 4% versus 0% (p = 0.06) and 3% versus 0% one year later (p = 0.12). Early postoperative reoperation rate for hemostasis was 2% versus 1% respectively (p = 0.25). We conclude that there is no significant difference in surgical morbidity between thyroidectomies for SG and cervical goiters when patients are operated in specialized centers. Operative fears are not justified.

[Treatment of diaphragmatic ruptures by laparoscopic approach in the lateral position]. / Traitement des ruptures de la coupole diaphragmatique par coelioscopie en décubitus latéral.

STUDY AIM: The aim of this retrospective study was to assess the feasibility of the treatment of recent diaphragmatic ruptures through laparoscopic approach in lateral position in patients with stable hemodynamic condition. PATIENTS AND METHOD: From 1994 to 1999, seven patients, 16 to 68 years old, were operated on for diaphragmatic rupture after a 6 hours to 15 days delay. Diaphragmatic rupture was located on the left side in 6 patients, on the right side in 1. Diagnosis was confirmed by CT-scan with reconstructions; there was no associated visceral injury. Patients were operated on by laparoscopic approach in lateral position, herniated viscera reintegrated by moderate pulling and diaphragmatic rupture repaired with non resorbable continuous suture. RESULTS: Stomach was the usual herniated viscera (n = 6); hemothorax was less than 300 cL; diaphragmatic rupture was 8 to 12 cm long. Duration of surgery was no more than 120 minutes. The seven patients after a two months to two years delay had normal chest X-rays. CONCLUSION: The laparoscopic approach in lateral position provides good visibility of the diaphragmatic lesions, easy reduction of herniated organs, complete thorax exploration and cleaning, and easy diaphragmatic repair. This technique is only feasible in patients with stable hemodynamic conditions and does not provide a complete abdominal exploration.