Evidence for Somatostatin receptor 2 in thyroid tissue.

Somatostatin receptor scintigraphy has found considerable interest for imaging thyroid tumours. Recently, also therapeutic application of Somatostatin analogues labelled with beta-emitting radionuclides has been suggested as treatment option for thyroid tumours with absent radioiodine uptake. Most of the radiolabelled analogues available show a predominant affinity for Somatostatin receptor subtype 2. This study reports on the in vitro characterisation of Somatostatin receptor subtype mRNAs in thyroid tumours and normal thyroid tissue by means of RT-PCR. Surgical samples of 21 patients were collected, and mRNA of 16 tumour and 17 control specimen was isolated. mRNA expression for Somatostatin, SSTR subtype 1-5, thyroid markers (NIS, TSH, Tg, TPO) and control markers (GAPDH, beta-actin) was determined. PCR results were correlated with immunohistochemistry staining using SSTR2 receptor specific antibodies. 94% of all samples expressed Somatostatin receptor mRNA with predominant expression of subtype 2, less predominant of subtype 5 and subtype 3. Somatostatin receptor subtype 2 mRNA expression correlated well with immunohistochemical staining pattern in 13/16 samples, SSTR2 immunohistochemistry was positive in 87% of the samples. Our results show that Somatostatin receptor 2 is predominantly expressed on thyroid tissue and is a valid target for treatment of thyroid tumours. Octreotide derivatives currently used in Nuclear medicine seem to be well suited to target receptors expressed in thyroid tumours.

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

AIM: To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). METHODS: Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. RESULTS: The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. CONCLUSIONS: Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

Videobronchoscopic guidance makes percutaneous dilational tracheostomy safer.

BACKGROUND: Percutaneous dilational tracheostomy (PDT) can be performed under either conventional bronchoscopic or videobronchoscopic guidance. Only the latter procedure provides the surgeon with direct visual information. This study prospectively assessed procedural parameters and complications of PDT guided by conventional bronchoscopy (CB) or videobronchoscopy (VB). METHODS: Consecutive intensive care unit (ICU) patients who underwent PDT were enrolled in this study. Videobronchoscopy was available in two ICUs, whereas CB was available in three ICUs. Demographic data, procedural variables, and complications were recorded. RESULTS: In this study, 36 patients underwent PDT guided by VB (group V), and 38 patients underwent PDT guided by CB (group C). The two groups were well matched in terms of gender, anatomic aspects, and positioning of the patient. Operating time, procedural difficulty, and extent of tracheal bleeding were not different between the two groups. Group V showed a tendency to younger age (p = 0.055). Surgeons significantly more often considered PTD to be "completely safe" in group V (92% vs 61% in group C). The skin incisions were smaller (p = 0.003), and the extent of stomal bleeding was less (p = 0.001). Complications were tendentiously less frequent in group V (5.5%) than in group C (23.7%; p = 0.062). CONCLUSIONS: The surgeon performing PDT guided by VB has a higher degree of safety, resulting in less bleeding than with PDT guided by CB.

Robot-assisted mediastinal parathyroidectomy.

We report the first case of robot-assisted thoracoscopic resection of a mediastinal parathyroid adenoma in the aorto-pulmonary window. Intervention planning was based on preoperative CT-MIBI image fusion, a new imaging modality that enabled reliable and precise localization of the parathyroid. The technique consists of taking MIBI-SPECT and CT separately, using a fixation unit that provides reproducible positioning of the patients head and neck. The data sets are then superimposed upon each other using special software. After the localization process, a minimally invasive operation was performed using the DaVinci operating robot. The procedure proved not only to be feasible but also safe and not time-consuming. The postoperative course was uneventful, and the patient was discharged 4 days postoperatively. Compared to conventional thoracoscopic surgery, the robotic operating system provides better visualization of the operating field and facilitates the movement of the instruments. Precise preoperative imaging enables the careful planning of robot-assisted surgery for ectopic parathyroids located at relatively inaccessible regions such as the anterior mediastinum.

Epidermal growth factor receptor as a novel therapeutic target in anaplastic thyroid carcinomas.

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.

Neopterin: a prognostic variable in operations for lung cancer.

BACKGROUND: We studied the prognostic value of preoperatively measured neopterin to predict survival of lung cancer patients. Neopterin is produced and secreted by interferon-gamma-stimulated monocytic cells. High urinary neopterin concentrations are found in patients with viral infections, allograft rejection episodes, and some malignant diseases. In various tumor types high urinary neopterin concentrations are associated with a worse prognosis. METHODS: Preoperative neopterin levels of 110 patients (29 women, 81 men) with lung cancer including 7 patients with small cell lung cancer were measured and related to the time of survival after operation. Patients with clinically suspected stage IIIB lung cancer were not operated and therefore not enrolled in this study. Infectious diseases were not apparent at the time of preoperative urine sampling. Median postoperative follow-up period was 17.4 months. RESULTS: In a univariate analysis, patients with a preoperative neopterin concentration of more than 212 micromol/mol creatinine (4th quartile) were determined to have a significantly lower survival probability. In a multivariate analysis, a neopterin concentration of more than 212 micromol/mol creatinine (p < 0.01) and T-stage status (p < 0.005) were determined to be significantly predictive variables for worse survival prognosis. CONCLUSIONS: Preoperative neopterin proved to be a reliable prognostic factor for survival. Immunology may provide an accurate assessment of tumor aggression and its clinical behavior. In this sense, neopterin can serve as an immunologically based estimation of malignant outgrowth. In patients who are operable by clinical tumor stage but have a high risk for operation, elevated preoperative neopterin may help in the decision for a nonoperative treatment.

Alterations of gut neuropeptides in gastroesophageal reflux disease are resolved after antireflux surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) may cause alterations of gut neuropeptides such as motilin and neurotensin that are known to control foregut motility. The aim of this study was to investigate whether these alterations may be resolved following antireflux surgery. METHODS: Basal and postprandial plasma levels of motilin and neurotensin were measured in 20 GERD patients preoperatively and 6 months after antireflux surgery. There were 9 patients with normal esophageal peristalsis and 11 with poor esophageal body motility. Eleven healthy subjects served as control group. RESULTS: GERD patients with poor esophageal body motility had low basal plasma levels of motilin and high levels of neurotensin. Postprandial motilin levels were significantly increased in these GERD patients. After antireflux surgery, all observed alterations of gut neuropeptides returned to normal values. CONCLUSION: Alterations of gut neuropeptides may be implicated in the pathophysiology of impaired esophageal peristalsis in GERD. Antireflux surgery restores normal physiology of gut neuropeptides. This may contribute to improvement of foregut motility in GERD, thus counteracting duodenogastric reflux.

Colostomy vs tube cecostomy for protection of a low anastomosis in rectal cancer.

BACKGROUND: Symptomatic anastomotic leakage is the most important surgical complication following rectal resection with intestinal anastomosis. Therefore, the routine use of a protective stoma is suggested by several authors. In our department 2 different techniques are performed to protect the anastomosis. Patients receive either a loop colostomy/ileostomy (C/I) or a tube cecostomy (TC). HYPOTHESIS: No significant difference is noted between C/I and TC for protection of a low anastomosis regarding clinical anastomotic leakage rate, reoperation rate for anastomotic leaks/fistulas, postoperative mortality, and permanent colostomy rate. By avoiding a second operation (for colostomy closure), median hospital stay should be significantly reduced. DESIGN: A retrospective review during 1985 to 1997. SETTING: Tertiary care center PATIENTS: One hundred fifty-eight patients who had undergone anterior resections for rectal cancer were studied. Protective C/Is were used in 19 patients; a TC was fashioned in 30 patients. MAIN OUTCOME MEASURES: Clinical anastomotic leakage rate, reoperation rate for anastomotic leaks/fistulas, postoperative mortality, permanent colostomy rate, and median hospital stay. RESULTS: The rate of anastomotic leaks (C/I, 16%; TC, 17%), fecal peritonitis (C/I, 0%; TC, 10%), reoperation for anastomotic leaks/fistulas (C/I, 0%; TC, 13%), permanent colostomies (C/I, 0%; TC, 7%), and postoperative mortality (C/I, 5%; TC, 0%) did not differ significantly in both groups. Median hospital stay was significantly reduced in patients with TC (C/I, 28 days; TC, 15 days). CONCLUSION: In our patients with low resections for rectal cancer, a C/I for protection of the anastomosis did not improve outcome significantly as compared with a TC. With a properly fashioned TC and adequate postoperative management a second operation (for colostomy closure) can be avoided and the overall hospital stay is significantly reduced.

Surgical therapy for primary hyperparathyroidism in patients with previous thyroid surgery.

BACKGROUND: In patients with primary hyperparathyroidism (HPTH) and previous thyroid operations, complications of parathyroidectomy are more frequent than in patients undergoing initial neck surgery. The aim of this study was to investigate the value of preoperative imaging with regard to its influence on the surgical strategy. METHODS: We retrospectively analyzed 17 patients with primary HPTH and previous thyroid surgery. Preoperatively 16 patients underwent sonography and/or scintigraphy. RESULTS: Sonography had an overall accuracy to correctly localize enlarged parathyroid glands of 80%, and scintiscanning had overall accuracy of 78.6%. The accuracy of localization was increased up to 84.6% if both diagnostic procedures were applied. In patients with normal thyroid residues the accuracy of sonography was 85.7%, and it was 100% if scintiscanning was used. CONCLUSIONS: Preoperative localization techniques in patients with primary HPTH and previous thyroid surgery have high accuracy. This allows for an imaging-directed operative strategy, thus preventing unnecessary bilateral neck explorations, which carry a high risk of recurrent laryngeal nerve injury.

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.

[Intestinal invagination due to endometriosis of the terminal ileum]. / Darminvagination durch Endometriose des terminalen Ileums.

HISTORY AND CLINICAL FINDINGS: A 39 year old female patient presented with nausea and crampy abdominal pain in the right lower quadrant. INVESTIGATIONS: Physical examination showed a markedly distended abdomen with a diffuse pain, punctum maximum in the right lower part of the abdomen and reduced peristalsis. Plain abdominal x-rays revealed slightly dilated loops of small bowel with air-fluid levels. Abdominal ultrasound revealed thickening of the bowel wall of the distal ileum and some free fluid. To exclude Crohn's disease, Sellink-computer tomography was performed, which also showed thickening of the wall of the terminal ileum and dilated bowel loops proximal to the underlying stenosis. DIAGNOSIS, TREATMENT AND COURSE: Intraoperatively, the terminal ileum was thickened by scar tissue and subtotally invaginated. Histologic investigation of the resected specimen showed submucosal endometriosis. CONCLUSION: Endometriosis of the small bowel should be considered carefully in the differential diagnosis of female patients of reproductive age who suffer from symptoms of ileus, dysmenorrhea and sterility.

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.

Secretoneurin in carcinoids of the appendix-immunohistochemical comparison with chromogranins A,B and secretogranin II.

BACKGROUND: The aim of the present study was to investigate immunohistochemically the distribution of secretoneurin, a novel 33 amino acid peptide, in comparison to chromogranin A, chromogranin B, and secretogranin II in carcinoids of the appendix. MATERIALS AND METHODS: Paraffin-embedded tissues from 47 carcinoids were incubated with antibodies specific for chromogranin A, chromogranin B, the secretogranin II derived peptide LF- 19, and secretoneurin. RESULTS: 44 tumors (94%) were positive for secretoneurin, whereas only 39 tumors (83%) were immunoreactive for chromogranin A. There was no significant correlation between neuropeptide expression and type of carcinoid, tumor size, vascular infiltration, serosal involvement or mesoappendiceal infiltration. CONCLUSIONS: Our investigations revealed that secretoneurin is detected more frequently than chromogranin A in carcinoids of the appendix. This supports the theory that tumor cells of appendiceal carcinoids are of a different origin than other midgut carcinoids. No special tumor entity with a characteristic secretoneurin-chromogranin pattern could be identified.

Tailored antireflux surgery for gastroesophageal reflux disease: effectiveness and risk of postoperative dysphagia.

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.

Obstructive ileus of large bowel is associated with low tissue levels of neuropeptides in prestenotic bowel segment.

The neuropeptides substance P, vasoactive intestinal polypeptide, and the recently discovered peptide secretoneurin are neurotransmitters of the intrinsic nervous system of the gut and effect gut motility. The aim of this study was to investigate whether these neuropeptides are involved in the pathophysiology of large bowel ileus. Five patients underwent colonic resections for obstructive cancer of the colon. Full-thickness specimens of the resected colon were taken 10 cm proximal and 10 cm distal to the site of tumor obstruction. Substance P-, vasoactive intestinal polypeptide-, and secretoneurin-like immunoreactivities were measured in the specimens by radioimmunoassay. In addition immunocytochemistry was performed. Tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin were lower in the prestenotic than in the poststenotic bowel segment. In accordance, immunocytochemistry revealed a denser staining of ganglion cells and fibers for all three neuropeptides in the poststenotic bowel. The decreased tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin in the prestenotic bowel segment may contribute to the final decompensation of obstructive ileus.

Survival and local recurrence after anterior resection and abdominoperineal excision for rectal cancer.

The aim of this retrospective study is to compare the outcome of abdominoperineal excision (APE) and anterior resection (AR) for rectal cancer in 136 patients. Local recurrence rates and 5-year survival probabilities were estimated for the AR and APE group. Further comparisons were carried out between hand-sewn and stapled anastomoses after AR, and between patients after AR and APE for tumours 2 to 6 cm from the dentate line. Local recurrence after AR occurred in 14% and after APE in 10% of these cases. Five-year survival probabilities and local recurrence frequencies showed no statistically significant difference (P > 0.05). Local recurrence rates were 13.5% after hand-sewn anastomoses and 15% after the stapled procedure. No statistically significant difference was observed in the 5-year survival and recurrence rate (P > 0.05). Seventy-four of 136 patients had tumours located 2 to 6 cm from the dentata line. Local recurrence occurred in 21% after AR and 5% after APE, showing a statistically significant difference in frequency (P < 0.05). No significant difference was found in cumulative 5-year survival probabilities. APE for advanced low rectal cancer showed a significant reduction in local recurrences compared to AR.

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.