Resection of pulmonary metastases from colon and rectal cancer: factors to predict survival differ regarding to the origin of the primary tumor.

BACKGROUND: The purpose of the present study was to determine differences in prognostic factors for survival of patients with pulmonary metastases resected in curative intent from colon or rectum cancer. METHODS: Between 1980 and 2006, prognostic factors after resection of pulmonary metastases in 171 patients with primary rectum or colon tumor were evaluated. Survival of patients after surgical metastasectomy was compared with that of patients receiving standard chemotherapy by matched-pair analysis. RESULTS: Median survival after pulmonary resection was 35.2 months (confidence interval 27.3-43.2). One-, 3-, and 5-year survival for patients following R0 resection was 88.8, 52.1, and 32.9 % respectively. Complete metastasectomy (R0), UICC stage of the primary tumor, pleural infiltration, and hilar or mediastinal lymph node metastases are independent prognostic factors for survival. Matched-pair analysis confirmed that pulmonary metastasectomy significantly improved survival. Although no difference in survival for patients with pulmonary metastases from lower rectal compared to upper rectal or colon cancer was observed, factors to predict survival are different for patients with lower and middle rectal cancer (R0, mediastinal and/or hilar lymph nodes, gender, UICC stage) compared with patients with upper rectal or colon cancer (R0, number of metastases). CONCLUSIONS: Our results indicate that distinct prognostic factors exist for patients with pulmonary metastases from lower rectal compared with upper rectal or colon cancer. This supports the notion that colorectal cancer should not be considered as a single-tumor entity. Metastasectomy, especially after complete resection resulted in a dramatic improvement of survival compared with patients treated with chemotherapy alone.

[Non-curable tumours of the female genital tract: therapeutic options in bowel stenosis and bleeding]. / Inoperable Genitaltumoren der Frau: Therapeutische Optionen bei Darmstenose und -blutung.

BACKGROUND: Tumours of the female genital tract are often diagnosed at an advanced stage or re-lapse after initial curative therapy. Ovarian cancer is in particular associated with peritoneal carcinomatosis or local tumour progression entailing different intestinal complications. MATERIAL AND METHODS: Based on our own results and a systemic PubMed search, different intestinal complications in non-curable tumours of the female genital tract were defined and different surgical and non-surgical therapeutic options were analysed. RESULTS: Stenosis of the small bowel is often caused by direct infiltration of the tumour. Peritoneal carcinomatosis or postoperative abdominal adhesions may lead to an acute or even more often chronic recurrent obstruction. The rectum or sigmoid colon is in particular affected by stenosis caused by tumour masses within the pelvis, occurring fistulas or direct tumour infiltration which may lead to bleeding complications or a large bowel obstruction. Radiation-induced abdominal adhesions or stenosis of the small bowel as well as radiation-induced chronic proctocolitis are further common abdominal complications. Special attention with regard to a well balanced indication towards surgical, oncological or conservative management must be given in the palliative setting of the genital tract. CONCLUSION: In particular the dictum of "primum nihil nocere" has to be followed in consideration of the patient's declared intention, the patient's prognosis, general condition, psychological strain as well as the expected complications.

[Tracheal stents for esophagotracheal fistula in laryngectomy patients. Safe fixation to the tracheostoma]. / Trachealstents wegen ösophagotrachealer Fistel beim Laryngektomierten. Sichere Fixierung am Tracheostoma.

BACKGROUND: Postradiotherapy or malignant esophagotracheal fistulas still represent a dilemma. In the absence of surgical options attempts are made to close the fistula endoscopically by means of esophageal and/or tracheal stents. Tracheal stent placement in laryngectomy patients with terminal stomas is particularly problematic due to the risk of stent dislocation during cannula replacement PATIENTS AND METHODS: Six laryngectomy patients with high esophagotracheal fistulas were each fitted with a coated Ultraflex stent (Boston Scientific, Watertown/MA, US). Following skin undermining, the stents were fixed to the tracheostoma with interrupted sutures and the skin flaps attached to the stent with a second row of sutures. RESULTS: Fistulas could be completely closed in all patients and there were no cases of stent dislocation. Cannula replacement was unproblematic. CONCLUSIONS: Suture fixation of tracheal stents is a viable procedure even for patients with esophagotracheal fistulas and terminal tracheostomy following laryngectomy.

Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones.

BACKGROUND: Recently it has been postulated that gallbladder mucin hypersecretion observed in the pathogenesis of cholesterol gallstone disease may be induced by biliary lipid peroxidation. Ursodeoxycholic acid treatment reduces mucin concentration and the formation of cholesterol crystals in the gallbladder bile of patients with cholesterol gallstones and this effect might be mediated by a decrease of biliary lipid peroxidation. MATERIAL AND METHODS: In a double-blind, placebo-controlled trial patients with symptomatic cholesterol gallstones received either ursodeoxycholic acid (750 mg daily) (n = 10) or placebo (n = 12) 10-12 days prior to cholecystectomy. As a marker for lipid peroxidation malondialdehyde was measured in bile together with mucin concentration. In addition, the mucin secretagogue activity of the individual bile samples was assessed in cultured dog gallbladder epithelial cells. RESULTS: Ursodeoxycholic acid therapy resulted in a significant reduction of lipid peroxidation in bile as determined by the biliary malondialdehyde concentration (1.36 +/- 0.28 vs. 2.05 +/- 0.38 micromol L(-1); P < 0.005) and the malondialdehyde (micromol L(-1))/total bile acid (mmol L(-1)) ratio (0.02 +/- 0.005 vs. 0.06 +/- 0.01; P < 0.001). Furthermore, a decrease in mucin concentrations (0.7 +/- 0.3 vs. 1.3 +/- 0.5 mg mL(-1); P < 0.005) and of the mucin secretagogue activity of gallbladder bile (0.9 +/- 0.2 vs. 2.2 +/- 0.3 times control; P < 0.001) was observed. CONCLUSIONS: The reduction of lipid peroxidation and mucin secretagogue activity of gallbladder bile induced by ursodeoxycholic acid treatment may contribute to the beneficial effects of this drug on gallbladder bile composition and symptoms in cholesterol gallstone patients.

Endoluminal vacuum therapy for the treatment of anastomotic leakage after anterior rectal resection.

Anastomotic leakage is the most important complication after (deep) anterior rectal resection, and is the main cause for the high level of patient mortality and morbidity. It can lead to generalized peritonitis, with a severe septic progression involving multiple organ failure and potentially culminating in the death of the patient. Despite numerous improvements in the surgical technique, it has so far not been possible to reduce the leakage rate significantly. An innovative endoscopic method for treating anastomotic leakage has now been developed and established clinically at the Department of Surgery, University of Munich-Grosshadern. Working together with B. Braun, we have been able to develop the technique of endoluminal vacuum therapy further into the Endo-SPONGE treatment, and prepare it as an autonomous therapeutic method. In the following report we present our experiences to date in the area of endoluminal vacuum therapy.

Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1.

BACKGROUND: Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting. OBJECTIVE: To optimize screening and to analyze possible differences in sporadic versus familial cases. METHODS: We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families). RESULTS: A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial-carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21%) were found to be the first presentation. APA occurred significantly more frequent (p<0,05) in isolated (n=138) than in familial (n=168) cases, whereas GEP showed a tendency to occur more often in familial cases. Genotype/phenotype correlation in 140 clinically affected MEN-1 cases showed a tendency for truncating mutations, especially nonsense mutations to be associated to GEP and carcinoids of the lungs and thymus. CONCLUSION: In view of the morbidity and frequency in familial cases an effective screening programme should aim at an early diagnosis of GEP particularly when truncating, especially nonsense mutations are found.

Transoral diverticulostomy with a modified Endo-Gia stapler: results after 4 years of experience.

BACKGROUND: The incidence of Zenker's diverticulum is low (2/100,000). Standard surgical treatment is cricopharyngeal myotomy with diverticulectomy. Various minimally invasive surgical approaches pursued recently have treated Zenker's diverticulum adequately. The functional minimally invasive therapy is performed alternatively using an Endo-Gia stapler inserted transorally to perform an esophageal diverticulostomia, or using thermal coagulation applied by a carbon dioxide (CO2) or argon plasma laser. The key to a successful procedure is adequate exposure of the diverticulum by insertion of a pharynx spreader before the surgery. METHODS: Since 1996, 31 patients who underwent minimally invasive diverticulostomies performed in our clinic have been included prospectively in the current study. All the patients were examined endoscopically before and after surgery. Furthermore, the intraesophageal and intragastric pressure was examined by transesophageal manometry, and the pH in the esophagus and stomach was determined by pH-metry. A barium swallow was performed to exclude leakage at the stapler suture line as proof of sufficient anastomoses. Manometry showed that the upper esophageal sphincter functioned normally before and after surgery. The results were compared with those of patients undergoing conventional procedures. RESULTS: The median follow-up period after resection of the diverticulum was 46 months. Both the Gastrointestinal Quality-of-Life Index (GQLI) (p < 0.001) and the modified dysphagia score (GHDS) increased significantly, indicating that the operations were successful. The minimally invasive procedure is faster than cricopharyngeal myotomy and significantly safer. It is better tolerated by patients, and they are discharged earlier. CONCLUSION: Transoral esophagodiverticulosomy has become the standard procedure for Zenker's diverticulum in the authors' department. The endoscopic minimally invasive approach proved to be safer than standard surgical procedures. It offers a significantly shorter operation time and postoperative hospital stay (p < 0.001).

Development of a cost-effective system for digital off-line analysis of transrectal ultrasound.

BACKGROUND: Transrectal ultrasound (TRUS) is the most sensitive and accurate technique for preoperative staging and follow-up of rectal cancer. One of the most relevant problems of this technique is that the assessment of TRUS is possible only during real-time examination. Furthermore, interpretation of the ultrasound findings is difficult and requires long experience. We show the development of a new, cost-effective software solution for off-line examination and documentation of transrectal ultrasound. METHODS: The ultrasound device is connected to a frame-grabber card in a standard PC. Video capturing is done using a freeware software solution and various video codecs. The whole examination course is recorded. The examiner only has to concentrate on producing an artifact-free realization of the examination. RESULTS: The software solution offers a flexible review of each individual "frame" of the investigation on the personal computer, very similar to CT and MRI scans. Infiltration depth and lymph node status can be assessed at any time, independently of the investigation and the investigator. The picture quality is excellent even if a lossy codec is used. It is not necessary to do definitive assessment of the TRUS during the examination. CONCLUSIONS: This new technique gives a cost-effective possibility for high-quality off-line staging, re-examination, re-evaluation, and documentation of rectal cancer. TRUS becomes an examiner-independent objective examination technique for staging and follow-up of rectal cancer.

High-energy shock waves induce blood flow reduction in tumors.

We have studied the effect of extracorporeally applied high-energy shock waves (HESW) on blood flow in amelanotic melanomas (A-Mel-3). Two tumors were implanted in the dorsal skin of 21 Syrian golden hamsters. One of the tumors was treated with 200 HESW, and the other served as an intraindividual control. Mean blood flow in the whole tumor, or the tumor excluding necrotic areas, was quantitatively measured using autoradiography with iodo[14C]antipyrine at 30 min (n = 5), 1 h (n = 5), 3 h (n = 5), and 12 h (n = 6) after HESW treatment. As measured for the whole tumor, blood flow in the controls was 23.4 +/- 7.9 ml/100 g/min (median +/- SE) and thus in the range reported in the literature. Thirty min or 1 h after the application of HESW, tumor perfusion was reduced to 6 +/- 4% or 5 +/- 4% (median +/- SE) of the corresponding controls, respectively. Three h after treatment, perfusion increased slightly to 7 +/- 5% and after 12 h increased significantly to 55 +/- 25% of the corresponding controls. Values measured excluding the necrotic areas were higher in all groups. Temporary reduction of tumor perfusion after treatment with HESW was interpreted as a consequence of HESW-induced damage to tumor microcirculation. These effects should be taken into account for maximizing the therapeutic efficiency of HESW on tumors and for combining HESW treatment with other therapeutical modalities.

Cytogenetic changes in radiation-induced tumors of the thyroid.

Thyroid carcinoma incidence is increased significantly after ionizing irradiation; however, the possible mechanisms have not yet been identified. To provide clues for an understanding of the radiation-induced transformation of thyroid epithelium, we analyzed the karyotypes of 56 childhood thyroid tumors that appeared in Belarus after the Chernobyl nuclear accident in 1986. We also studied eight secondary thyroid tumors that developed after radiotherapy. Metaphase preparations obtained from primary cultures were analyzed by G-banding. Clonal structural aberrations were found in 13 of 56 Belarussian cases and in 6 of 8 secondary tumors that developed after radiotherapy. Furthermore, we detected multiple chromosomal aberrations as well as complex rearrangements in some of these tumors and performed a detailed analysis of marker chromosomes from a single case using spectral karyotyping and comparative genomic hybridization in a childhood tumor from Belarus with a near-triploid karyotype. Both comparative genomic hybridization and spectral karyotyping analysis revealed structural alterations affecting identical chromosomes 1, 2, 9, and 13, among others. In addition to the known hot spots of alterations in papillary thyroid carcinomas on chromosomes 1q and 10q, a comprehensive breakpoint analysis in the pooled data set revealed novel breakpoints on chromosomes 4q, 5q, 6p, 12q, 13q, and 14q. The chromosomal aberrations in these tumors may provide suitable starting points for the positional cloning of genes involved in radiation-induced tumorigenesis.

Increased leukotriene B4 synthesis in patients with primary hyperparathyroidism is normalized after parathyroidectomy: a study comparing parathyroidectomy to thyroid adenomectomy.

Synthesis of leukotriene B4 (LTB4) upon stimulation of peripheral blood samples with the calcium ionophore A 23187 was studied in patients with primary hyperparathyroidism who underwent parathyroidectomy. Preoperatively, an increased LTB4 concentration of 1.76 +/- 0.19 ng/ml plasma was found, vs. 0.95 +/- 0.28 ng/ml in healthy individuals. On the fourth day after operation, the LTB4 concentration was almost normalized, reaching 1.25 +/- 0.23 ng/ml plasma. At the same time, mean serum calcium levels were reduced from 6.1 +/- 0.6 meq/liter before operation to 4.53 +/- 0.28 meq/liter after operation. In a control group, euthyroid patients with thyroid adenomas who underwent adenomectomy had normal LTB4 levels before operation (0.84 +/- 0.11 ng/ml) and did not show significant changes in LTB4-synthesizing capacity. The results indicate that synthesis of LTB4 in vivo may depend in part on factors related to serum calcium concentration or calcium metabolism.

Sporadic pheochromocytomas are rarely associated with germline mutations in the vhl tumor suppressor gene or the ret protooncogene.

Pheochromocytoma is a tumor that may occur sporadically or may be a manifestation of a hereditary disease, such as von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia (MEN) type 2. As patients with VHL or MEN type 2 are at risk to develop multiple tumors, they must be distinguished from sporadic cases. We determined the incidence of VHL and MEN type 2 among 62 German patients diagnosed with pheochromocytoma without a history of a hereditary disease. Germline analyses of the vhl gene and exons 10, 11, and 13 of the ret protooncogene were performed by PCR, single strand conformation polymorphism, enzyme digestion, or sequencing. Two patients (3%) showed vhl mutations (95% confidence interval, 1-11%). One patient showed loss of the MspI restriction site at nucleotides 712/713. Another patient had a C/T change at an intronic site that was also detected in 2 of his offspring. No mutations were detected in the ret protooncogene (97.5% confidence interval, 0-6%). In Germany, most sporadic pheochromocytomas are not due to VHL or MEN type 2. Therefore, clinical work-up in patients with pheochromocytoma without signs of hereditary disease is not recommended. However, because the costs of genetic screening are relatively low, and each index case allows optimal care for family members, molecular testing might be cost-effective.

Biliary concentrations of temocillin.

Serum and bile concentrations of temocillin were measured after intravenous administration of 1g twice daily to 16 patients with biliary tract infections. The concentration of temocillin in the bile showed high inter-individual variations; however, in patients drug concentrations were attained which were considerably higher than the minimum inhibitory concentrations of the biliary tract pathogens identified throughout the study period. All the patients admitted to the study were treated successfully by temocillin, with the tolerance of the drug being very good, and no side effects or drug-related deteriorations of laboratory data being reported.

Cytogenetic and molecular genetic characterization of a chromosome 2 rearrangement in a case of human papillary thyroid carcinoma with radiation history.

Karyotype analysis of a primary culture from a case of papillary thyroid cancer (PTC) showed an abnormal short arm of one homologue of chromosome 2 as sole abnormality in 4 of 16 metaphases. Based on G-banding analysis, two different aberration types on chromosome 2 could be assumed representing either a del(2)(p22-23) or a pericentric inversion. Further comparative genomic hybridization (CGH) analysis as well as fluorescence in situ hybridization (FISH) analysis were performed to confirm the assumed alterations. While CGH analysis showed no loss of chromosome 2 material, FISH with yeast artificial chromosome (YAC) probes homologous to the region 2p22-23 demonstrated two pericentric inversions of chromosome 2 involving different breakpoints on 2p in 6.8% and 4.2% of the metaphases, respectively. Polymerase chain reaction (PCR) analysis with degenerated oligonucleotide primers that bind within the conserved catalytic domain of tyrosine kinase (tk) genes resulted in amplification products with DNA of YAC 851D11 suggesting the presence of such genes at or near the translocation breakpoint.

Asymptomatic hypercalcemia due to an ectopic parathyroid adenoma in an 8-year-old boy.

The diagnosis of primary hyperparathyroidism in children is often delayed and is usually based on symptoms of hypercalcemia rather than abnormal laboratory values alone. We report the case of an 8-year-old boy with hypercalcemia, hypophosphatemia and mildly, but inadequately elevated intact parathyroid hormone (iPTH) who presented without any symptoms of hyperparathyroidism. Although imaging studies were misleading and four normal parathyroid glands were found intraoperatively, exploration of the thymus revealed an ectopic parathyroid adenoma. After removal of the ectopic gland, a rapid iPTH immunoassay proved immediate normalization of iPTH. This is the first report of sporadic isolated primary hyperparathyroidism diagnosed in an asymptomatic child on the basis of hypercalcemia and hypophosphatemia.

Intraoperative biochemical localization of insulinomas by quick radioimmunoassay.

In patients with organic hyperinsulinism, intraoperative determination of insulin concentrations in veins draining the pancreas might help localize the tumor. We have developed a radioimmunoassay measuring insulin within 30 minutes. At operation, blood samples are taken at various sites in the splenic, superior mesenteric and portal veins for insulin determinations. In all six patients, the highest insulin concentrations correlated with the site of the tumor. Also, small insulinomas less than 1 cm in diameter could be found. In one patient the tumor appeared to secrete mainly proinsulin. By this procedure we hope to avoid blind distal resection of the pancreas and possibly invasive preoperative diagnostic procedures.

Chromosome translocations in thyroid tissues from Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting.

Chromosome painting of chromosomes 1, 4 and 12 was performed on metaphase preparations of cultured thyroid cells to analyse the frequency of radiation-induced stable chromosome translocations in papillary thyroid carcinomas from 40 Belarussian children exposed to radioiodine from the Chernobyl accident, and from 31 reference case. As expected, we found the highest translocation frequencies in secondary thyroid tumours after radiotherapy, but there were also high frequencies in tumour tissues as well as in non-tumourous tissues from childhood papillary carcinoma samples from Belarus. Among the Belarussian tumours the cases from the Gomel region exhibited the highest frequency of translocations and five cases lie within the range of frequencies observed in secondary thyroid tumours after radiotherapy. The findings support the assumption that radiation was the principal cause of the tumours in Belarus, but they indicate also that only a minority of the Belarus cases, which have developed papillary carcinomas, were exposed to very high doses of radioiodine.

[Preoperative localization of the parathyroid glands with computerized tomography]. / Präoperative Lokalisationsdiagnostik der Nebenschilddrüsen mit der Computertomographie.

CT was carried out in 50 patients with clinical suspicion of hyperparathyroidism, in order to localise the adenoma. In 45 patients, the diagnosis was confirmed at operation and adenomas or hyperplastic glands were removed. In the remaining five patients the diagnosis was not confirmed at operation, nor by the subsequent clinical course. On four occasions, CT correctly turned out to be negative and in one patient a false positive finding was obtained. Amongst the 45 patients, a total of 59 enlarged glands (adenomas or hyperplastic glands) were found at operation and removed. Pre-operative CT was positive and correct in 78% and negative and incorrect in 22%. Of eight adenomas in the mediastinum, seven could be recognised pre-operatively. Previous operations on the neck did not reduce diagnostic accuracy. The techniques and results are described and discussed.

[Sonographic diagnosis of enlarged parathyroid glands in hyperparathyroidism (author's transl)]. / Sonographische Diagnostik vergrösserter Nebenschilddrüsen beim Hyperparathyreoidismus.

Fifty-nine patients suspected clinically of having primary or tertiary hyperparathyroidism have been examined since 1978 in order to localize enlarged parathyroid glands. With glands larger than 5 mm. this proved successful in about 90% of those situated in the neck. The sonographic features of enlarged parathyroid glands are poor echoes, smooth margins and the typical position on the medial and posterior surface of the thyroid gland. A requirement for diagnostic success is the use of modern compound apparatus with digital convertors and focussed high resolution probes.