Rupert Prommegger

Tailored Antireflux Surgery for Gastroesophageal Reflux Disease: Effectiveness and Risk of Postoperative Dysphagia

Abstract The Nissen fundoplication is not the proper antireflux procedure for patients with poor esophageal peristalsis as it does not strengthen impaired esophageal peristalsis. The aim of this study was to investigate if tailoring of antireflux surgery according to esophageal contractility is an effective treatment of gastroesophageal reflux disease (GERD) with a low incidence of postoperative dysphagia. The Toupet fundoplication was laparoscopically performed on 32 patients with poor esophageal peristalsis and the Nissen fundoplication on 17 patients with normal peristalsis. After a median follow-up of 15 months, only 1 of the 49 patients (2.04%) complained of heartburn. Acute esophagitis was found in none of them on endoscopy. Of 40 patients tested postoperatively, 2 (5%) underwent pathologic esophageal pH monitoring. Postoperative dysphagia was found in two patients (4.1%) compared with 25 (51%) preoperatively ( p < 0.05). There was a significant reduction of dysphagia following the Toupet fundoplication. Both procedures increased the resting pressure of the lower esophageal sphincter (LES) significantly, which was more pronounced following the Nissen fundoplication. Relaxation of the LES was significantly better following the Toupet than after the Nissen fundoplication. There was significant improvement of esophageal peristalsis following the Toupet fundoplication. Tailored antireflux surgery is an effective strategy for treatment of GERD. The incidence of postoperative dysphagia is low owing to improvement of impaired esophageal peristalsis following the Toupet fundoplication. It may be due to the fact that the Toupet fundoplication causes less esophageal outflow resistance than the Nissen fundoplication.

CT-MIBI image fusion: a new preoperative localization technique for primary, recurrent, and persistent hyperparathyroidism.

BACKGROUND Successful minimally invasive or imaging-guided operations in patients with primary, recurrent, and persistent hyperparathyroidism are based on the reliability of preoperative parathyroid localization studies. The CT-MIBI image fusion promises a higher diagnostic accuracy than current imaging procedures. The aim of our study was to assess its reliability in correctly detecting enlarged parathyroid glands. METHODS In a prospective study 24 consecutive patients underwent CT-MIBI image fusion as preoperative parathyroid localization procedure. The results of technetium 99m sestamibi single photon emission computed tomography (MIBI-SPECT) alone, today the standard method in parathyroid imaging, and CT-MIBI image fusion were analyzed by a blinded reviewer, and the imaging results were compared with the intraoperative findings. RESULTS For CT-MIBI image fusion a sensitivity of 93% and a specificity of 100% in correctly detecting the position of enlarged parathyroid glands was calculated and compared with a sensitivity of MIBI-SPECT of 31% and a specificity of 87% (P<.001). This new imaging technique enabled us to successfully treat 22 of our patients (92%) with imaging-guided surgery. Twenty (83%) underwent unilateral or minimally invasive operations. CONCLUSIONS CT-MIBI image fusion appears to be superior to MIBI-SPECT in preoperative parathyroid imaging. CT-MIBI image fusion can be performed on existing CT- and MIBI-SPECT units. We recommend this method for preoperative localization in patients with primary, recurrent and persistent hyperparathyroidism.

Retrospective evaluation of carcinoid tumors of the appendix in children

Carcinoids of the appendix are rare in children and are usually diagnosed incidentally on histologic investigation following appendectomy for appendicitis. To investigate the significance of the diagnosis of appendiceal carcinoid in children, we conducted a retrospective study of the treatment and follow-up of 36 children with histologically confirmed carcinoid tumors of the appendix. Between 1970 and 2000 a total of 36 patients (25 girls, 11 boys) were diagnosed with appendiceal carcinoid. The median age of the patients at diagnosis was 12.3 years (range 6–16 years). The indication for appendectomy was acute lower right quadrant pain in 27 cases and chronic right lower quadrant pain in 9 patients. In 27 specimens the tumor was localized at the apex, in 7 at the midportion, and in 2 at the base of the appendix. The median tumor diameter was 6 mm (range 3–17 mm). Concomitant severe appendicitis was diagnosed in 14 patients 2 with a perforated appendicitis. In only one tumor were mucin-producing cells detectable. After a median follow-up of 10 years (range 2 months to 30 years) all patients were tumor-free. None of the patients had a synchronous or metachronous noncarcinoid malignant tumor. Appendiceal carcinoids are usually asymptomatic, and the indication for surgical Intervention is acute or chronic abdominal pains in the right lower quadrant. For most patients the prognosis is excellent after appendectomy. As in adults, appendectomy is the appropriate treatment.RésuméLes tumeurs carcinoïdes de l’appendice sont rares chez l’enfant et sont diagnostiqués habituellement de façon fortuite sur la pièce d’appendicectomie réalisée pour syndrome appendiculaire. Afin d’évaluer la signification du diagnostic de tumeur carcinoïde chez l’enfant, nous avons réalisé une étude rétrospective du traitement et du suivi chez 36 enfants porteurs d’une tumeur carcinoïde de l’appendice. Entre 1970 et 2000, on a fait le diagnostic de tumeur carcinoïde de l’appendice chez 36 patients, 25 filles et 11 garçons, dont l’âge médian au moment du diagnostic a été de 12.3 ans (extrêmes: 6–16 ans). L’indication de l’appendicectomie a été une douleur aiguë de la fosse iliaque droite dans 27 cas et une douleur chronique de la fosse iliaque droite chez 9 patients. En ce qui concerne la localisation de la tumeur, sur 27 pièces, la tumeur a été localisée à la pointe dans 18 cas, dans la portion moyenne pour sept cas, et chez deux, à la base. La médiane du diamètre a été de 6 mm (extrêmes: 3–17 mm). Chez 14 patients on a diagnostiqué une appendicite sévère concomitante, deux fois avec perforation. On a détecté des cellules riches en mucine dans une seule tumeur. Après un suivi d’une médiane de 10 ans (extrêmes: 2 mois-30 ans,) tous les patients étaient sans tumeur. Aucun des patients n’a eu de tumeur maligne non carcinoïde synchrone ou métachrone. Les tumeurs carcinoïdes de l’appendice sont habituellement asymptomatiques et l’indication d’intervention chirurgicale est la douleur aiguë ou chronique de la fosse iliaque droite. Pour la plupart des patients, le pronostic est excellent après appendicectomie. Comme chez l’adulte, l’appendicectomie est le traitement approprié.ResumenEn el niño los tumores carcinoides de apéndice son muy raros y se diagnostican al efectuar el estudio histopatolôgico del apéndice extirpada por apendicitis. Para averiguar la transcendencia clïnica del carcinoide apendicular infantil, se realiza un estudio retrospectivo del tratamiento y evolución clïnica de 36 niños con diagnôstico de carcinoide apendicular confirmado histopatológicamente. Entre 1970 y 2000, 36: 25 niñas y 11 niños, fueron diagnosticados de carcinoma apendicular. La edad media de los pacientes fue 12.3 años (rango 6–16 años). La indicación de apendicectomia vino dada, en 27 casos por dolor agudo en el cuadrante inferior derecho y en 9 por molestias crónicas. En 27 especïmenes el tumor estaba situado en el apex, en 7 en la porción media y en 2 en la base apendicular. El diámetro medio del tumor fue de 6 mm (rango 3–17 mm). En 14 casos el carcinoide coincidïa con una apendicitis aguda y en 2 con apendicitis perforada. En sólo un tumor se detectaron células productoras de mucina. Tras un seguimiento medio de 10 anos (rañgo 2 meses-30 años) todos los pacientes estaban sanos. Ninguno desarrolló tumores malignos no carcinoides ni sincrónicos ni metacrónicos. Los carcinoides apendiculares son, por lo general, asintomáticos y la indicación quirúrgica se establece por dolor agudo o crónico en el cuadrante inferior derecho. Para la mayoría de los pacientes el pronóstico, tras apendicectomía, es excelente. Al igual que en los adultos, la apendicectomía constituye el tratamiento de elección.

Virtual neck exploration: a new method for localizing abnormal parathyroid glands.

Background Data:Computed tomography (CT) together with 99mTc-sestamibi single photon emission computed tomography (MIBI-SPECT) image fusion (CT-MIBI-SPECT image fusion) allows virtual exploration of the neck. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT and CT in detecting abnormal parathyroid glands in patients with primary hyperparathyroidism. Methods:CT-MIBI-SPECT image fusion for preoperative localization was performed in 116 patients with primary hyperparathyroidism (pHPT). Both investigations were performed with reproducible fixation of the patient on a vacuum mattress. At a special work station the neck was virtually explored by viewing the CT images in all 3 dimensions. The MIBI-SPECT images were superimposed on underlying CT images. Only patients with single-gland disease were evaluated (pHPT: 112, persistent pHPT: 1, recurrent pHPT: 1, persistent secondary hyperparathyroidism: 1, tertiary HPT after kidney transplantation: 1). CT-MIBI-SPECT image fusion results were compared with those obtained with CT alone and MIBI-SPECT alone. The predicted positions were correlated with the intraoperative findings. Results:CT-MIBI-SPECT image fusion was able to predict the exact position of the abnormal gland in 102 (88%) of the 116 patients, whereas CT alone showed in 75 (65%) patients and MIBI-SPECT alone in 64 (55%) patients the exact position of the abnormal gland. Sixty-two patients underwent minimally invasive surgery, namely in 21 patients with a unilaterally focused approach and in 33 patients with a bilateral approach (27 of these underwent simultaneous thyroid resection). Sensitivity for CT-MIBI-SPECT image fusion was 88%, for CT alone 70%, and for MIBI-SPECT alone 59%. Specificity for CT-MIBI-SPECT image fusion was 99%, for MIBI-SPECT alone 95%, for CT alone 94%. Overall accuracy for CT-MIBI-SPECT image fusion was 97%, for CT alone 89%, for MIBI-SPECT 87%. Conclusions:This study provides evidence that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone for preoperative localization of enlarged parathyroid glands in patients with single-gland primary hyperparathyroidism.

Epidermal Growth Factor Receptor as a Novel Therapeutic Target in Anaplastic Thyroid Carcinomas

Abstract: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies, with a median survival of up to 6 months. Such a bad prognosis under the present treatment procedures suggests the need for novel approaches in the management of this disease. Since some epidermal growth factor receptor (EGFR) inhibitors are now in clinical trials and few data are available concerning EGFR expression in anaplastic thyroid carcinomas, we tried to estimate a possible overexpression of this receptor in a larger tumor series. Twenty‐five ATCs, including 3 ATCs with poorly differentiated thyroid carcinoma (PDTC) parts, were immunohistochemically investigated with a mouse monoclonal antibody directed against EGFR (EGFR pharmDX kit). The tumors revealed primarily a distinct membranous staining pattern, and in several tumor cells an additional cytoplasmic reactivity could be observed. The anaplastic carcinomas presented with 5 of 25 (20%) without EGFR reaction, 10 of 25 (40%) with reactivity, and 10 of 25 (40%) with overexpression of the receptor. All ATCs with PDTC parts (100%) showed EGFR overexpression. Cytoplasmic reactivity was observed in 56% of all ATCs. A significant correlation was calculated for EGFR overexpression and cytoplasmic staining (P= 0.036). Concerning receptor overexpression, ATCs were significantly different from ATCs with PDTC parts (P= 0.023). For the first time, we present EGFR overexpression in ATC in a larger tumor series, demonstrating that EGFR overexpression is a common finding in ATC. For at least one‐third of all anaplastic thyroid carcinomas, EGFR seems to be a promising agent for the targeted molecular therapy of these extraordinarily aggressive tumors.

Laparoscopic partial posterior fundoplication provides excellent intermediate results in GERD patients with impaired esophageal peristalsis.

BACKGROUND Gastroesophageal reflux disease (GERD) is frequently associated with impaired esophageal peristalsis, and many authorities consider this condition not suitable for Nissen fundoplication. METHODS To investigate the outcome of antireflux surgery in the presence of impaired esophageal peristalsis, 78 consecutive GERD patients with poor esophageal contractility who underwent laparoscopic partial posterior fundoplication were studied. A standardized questionnaire, upper gastrointestinal endoscopy, esophageal manometry, and 24-hour pH monitoring were performed preoperatively and at a median of 31 months (range 6-57 months) postoperatively. Esophageal motility was analyzed for contraction amplitudes in the distal two thirds of the esophagus, frequency of peristaltic, simultaneous, and interrupted waves, and the total number of defective propagations. In addition, parameters defining the function of the lower esophageal sphincter were evaluated. RESULTS After antireflux surgery, 76 patients (97%) were free of heartburn and regurgitation and had no esophagitis on endoscopy. The rate of dysphagia decreased from 49% preoperatively to 10% postoperatively (P < .001). Features defining impaired esophageal body motility improved significantly after antireflux surgery. The median DeMeester score on 24-hour esophageal pH monitoring decreased from 33.3 to 1.1 (P < .001). CONCLUSIONS Partial posterior fundoplication provides an effective antireflux barrier in patients with impaired esophageal body motility. Postoperative dysphagia is diminished, probably because of improved esophageal body function.

Long-term results of surgery for adenoid cystic carcinoma of the trachea and bronchi

AIMS Over a period of 26 years, 16 patients (9 women, 7 men) underwent surgery for primary adenoid cystic carcinoma (ACC) of the trachea and bronchi. The median age at diagnosis was 41.4 years (range 25-67). Nine tumours were located in the bifurcational area, five in the trachea, one in the middle-lobe bronchus and one in the parenchyma of the left lower lobe. METHODS Surgical procedures were as follows: three tracheal transversal resections; five resections of the distal trachea including the bifurcational region, followed by bifurcational reconstruction; two right-sleeve pneumonectomies; three left-sleeve pneumonectomies; two lobectomies; and one explorative sternotomy. RESULTS Eleven patients were available for follow-up at least 5 years after surgery. Three of these patients (27%) had local recurrence 155+/-30 (range 120-175) months after surgery. Distant metastases occurred in six patients (55%) after a median time interval of 96+/-68 (range 24-180) months after surgery. CONCLUSIONS Five-year and 10-year survivals were excellent, 79 and 57% respectively, but the long-term outcome was poor due to late local recurrences and late metastatic spread. It is not yet certain whether a cure can really be achieved in ACC.

CT-MIBI-SPECT image fusion predicts multiglandular disease in hyperparathyroidism

BackgroundTo perform focused or minimally invasive surgery for hyperparathyroidism (HPT) exact preoperative localization is mandatory. Computed tomography–99mTc-sestamibi–single photon emission computed tomography image fusion (CT-MIBI-SPECT) serves this difficult task in single gland HPT to a large extent. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone and CT alone in detecting abnormal parathyroid tissue in patients with multiglandular disease.Patients and methodsCT-MIBI-SPECT image fusion for preoperative localization was performed in 30 patients with multiglandular disease. There were six patients with primary hyperparathyroidism (four MEN I syndromes and two double adenomas; one of these patients has HRPT2 gene mutation), 14 with secondary, and eight with tertiary HPT, further one patient each suffering from persistent primary and persistent secondary hyperparathyroidism. In both persistent patients only one remaining gland was left from primary surgery. The results of MIBI-SPECT, CT, and CT-MIBI-SPECT image fusion were compared in these patients. The outcome and the exact predicted positions were correlated with intraoperative findings.ResultsIn five out of six patients with multiglandular primary hyperparathyroidism more than one gland was detected, thus multiglandular disease could be suspected preoperatively. Overall CT-MIBI-SPECT image fusion was able to predict the exact position of all abnormal glands per patient in 14 of 30 (46.7%) cases, whereas CT alone was successful in 11 (36.7%), and MIBI-SPECT alone just in four (13.3%) of 30 patients.ConclusionMultiglandular disease in primary hyperparathyroidism can be suspected preoperatively in a high percentage of patients. Additionally, this study shows that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone in preoperative localization of all pathologic glands in patients suffering from multiglandular disease.

EpCAM overexpression in thyroid carcinomas: a histopathological study of 121 cases.

Epithelial cell adhesion molecule (EpCAM) is expressed by a broad variety of carcinoma cells. It is recognized by the monoclonal antibody 17-1A, which has already been applied for immunotherapy of several carcinoma types in preclinical and small clinical studies. In the present study the immunohistochemical properties of 17-1A were evaluated in 121 cases of thyroid carcinomas of follicular cell origin, comprising of 75 differentiated (DTC; 35 papillary and 40 follicular carcinomas), 24 poorly differentiated (PDTC) and 22 anaplastic thyroid carcinomas. Overexpression of EpCAM, as recently defined, was found with a distinct membranous staining pattern in 81.3% of DTCs and in 66.6% of PDTCs. In contrast, all anaplastic thyroid carcinomas (0%) completely lacked EpCAM expression. Normal thyroid tissue presented with weak and heterogeneous EpCAM staining. This study demonstrates EpCAM overexpression as a common finding in DTCs and PDTCs, and thus these tumors as possible novel targets for EpCAM-directed immunotherapy. Our findings suggest that patients with recurrent or advanced tumor disease and metastatic spread could benefit from this modern therapeutic regime, especially after insufficient radioiodine therapy.

Effect of anticonvulsant treatment on kainic acid-induced increases in peptide levels.

The influence of anticonvulsant treatment upon (1) chronically increased seizure susceptibility, (2) on late increases in peptide levels and (3) on seizure-induced brain damage was investigated during various stages of acute kainic acid (10 mg/kg i.p.)-induced seizures. The seizures were interrupted at various stages of the syndrome (50 min to 24 h after injection of the toxin) by injecting thiopental (50 mg/kg i.p.) or the excitatory amino acid antagonist, MK-801 (10 mg/kg i.p.). The increase in neuropeptide Y and somatostatin levels in the frontal cortex could be prevented by early injection of either anticonvulsant (up to 180 min after kainic acid). No protection against the increase in peptide levels was observed when the anticonvulsants were applied later. Kainic acid-induced neuronal damage in the amygdala, with glutamate decarboxylase as a neurochemical marker, was entirely prevented by interrupting seizures up to 2 h after kainic acid. Partial protection (about 40-50%) was even found when the anticonvulsant treatment was applied after the acute syndrome, as late as 8 h after kainic acid injection. Chronically increased seizure susceptibility induced by kainic acid was not prevented, even by early injection (90 min after kainic acid) of the anticonvulsant drugs. The data indicate that (1) the late increase in seizure susceptibility may be initiated early after injection of kainic acid. (2) the late increase in peptide levels may be related to the frequency of acute seizures rather than to a change in seizure threshold or brain damage and (3) even late anticonvulsant therapy may antagonize seizure-induced brain damage in the amygdala.