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1.
Minerva Surg ; 77(3): 205-213, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34338458

ABSTRACT

BACKGROUND: Due to the lack of perioperative standards in thyroid surgery, this study aimed to evaluate the perioperative management and wound closure techniques used in a nationwide survey. METHODS: A questionnaire evaluating preferred technique in thyroid resection, postoperative management, and the occurrence of complications was sent to all hospitals in Germany performing more than 50 thyroid operations p.a. (N.=362, response rate 78% [N.=283]). Subsequently, hospitals were subdivided into university and maximum care hospitals (Category A, N.=54) and tertiary hospitals and basic care hospitals (Category B, N.=229). RESULTS: According to our results, 10.6% of the hospitals were certified as a center for thyroid surgery, with a significantly higher percentage in Category A (20.4% vs. 8.3%; P<0.01). Concerning the surgical techniques, Kocher's incision was the favored cervical approach in 96% of the hospitals. A minimally invasive approach was performed in 30.1%, with a significantly more common description in Category A; 97.8% of all clinics stated that they perform a platysma muscle suture, primarily as a single stitch interrupted. Skin closure was predominantly performed via intracutaneous suture in 84.5% using absorbable suture material in 63.1%. There was no difference in the technology used in terms of hospital size. The mean in-hospital stay was significantly shorter in Category A hospitals (P=0.035). CONCLUSIONS: The suture technique used in thyroid surgery in Germany is a simple interrupted suture technique for platysma and a continuous suture with absorbable skin closure material. Maximum care hospitals are characterized by shorter in-hospital stays and improved quality assurance.


Subject(s)
Sutures , Thyroid Gland , Germany , Humans , Surveys and Questionnaires , Suture Techniques , Thyroid Gland/surgery
2.
World J Surg ; 39(7): 1750-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25665676

ABSTRACT

BACKGROUND: Precise preoperative localization is essential for focussed parathyroidectomy. The imaging standard consists of cervical ultrasonography (cUS) and (99m)Tc-MIBI-SPECT (MIBI-SPECT). (11)C-methionine positron emission tomography/computed tomography (Met-PET/CT) is a promising method for localizing parathyroid adenomas. The objective of our study was to elucidate whether additional Met-PET/CT increases the rate of focussed parathyroidectomy. METHODS: Fourteen patients with primary hyperparathyroidism (HPT) and three patients with tertiary HPT underwent cUS and MIBI-SPECT. Met-PET/CT was carried out in patients with negative MIBI results. Subsequent surgical strategy was adapted according to imaging results. RESULTS: cUS localized a single parathyroid adenoma in 10/17 patients (59 %), while MIBI-SPECT/CT identified 11/17 single adenomas (65 %). In the remaining six patients, Met-PET/CT identified five single adenomas. This step-up approach correctly identified single adenomas in 16/17 patients (94 %). CONCLUSION: Met-PET/CT raises the rate of correctly localized single parathyroid adenomas in patients with negative cUS and MIBI-SPECT/CT and increases the number of focussed surgical approaches.


Subject(s)
Adenoma/diagnostic imaging , Adenoma/surgery , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Parathyroidectomy , Tomography, Emission-Computed, Single-Photon/methods , Aged , Carbon Radioisotopes , Female , Humans , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/etiology , Male , Methionine , Middle Aged , Preoperative Period , Sensitivity and Specificity , Technetium Tc 99m Sestamibi , Ultrasonography
3.
J Gastrointest Surg ; 17(6): 1058-65, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23400507

ABSTRACT

BACKGROUND: In contrast to conventional Through-the-Scope Clips, the novel Over-the-Scope Clip (OTSC(®)) allows endoscopic full thickness closure of gastrointestinal leakages. The purpose of this study was to evaluate the efficacy and safety of the OTSC for the management of postoperative gastrointestinal leakages and fistulas. METHODS: We retrospectively reviewed a series of 14 consecutive patients with postoperative gastrointestinal leakages and fistulas who were treated by OTSC application. RESULTS: Nine OTSCs were used for upper GI tract leakages; five were used for colorectal leakages. Seventy-nine percent (11/14) of leakages were chronic (treated by OTSC later than postoperative day 14). In nine patients, other therapies preceded OTSC application. Median follow-up time was 5.5 months (range, 0.25-17). Primary technical success was achieved in all (14/14) patients. No adverse events related to the use of the OTSC device were noted. Three early recurrences were observed (two colonic fistulas, one esophageal anastomotic leakage), leading to a long-term success rate of 79 % (11/14). Leakage closure finally was achieved in these three patients by surgery or endoscopic vacuum therapy. CONCLUSIONS: The OTSC system is an effective and safe method for the management of postoperative leakages and fistulas of the gastrointestinal tract. Its exact place in treatment algorithms of postoperative leakages will have to be determined.


Subject(s)
Anastomotic Leak/surgery , Endoscopy, Gastrointestinal/instrumentation , Esophagus/surgery , Fistula/surgery , Adult , Aged , Anastomosis, Surgical/adverse effects , Anastomotic Leak/etiology , Bronchial Fistula/surgery , Colonic Diseases/surgery , Cutaneous Fistula/surgery , Digestive System Fistula/surgery , Female , Humans , Male , Middle Aged , Pleural Diseases/surgery , Recurrence , Retrospective Studies , Stomach Diseases/surgery
4.
EJNMMI Res ; 2(1): 51, 2012 Sep 27.
Article in English | MEDLINE | ID: mdl-23014191

ABSTRACT

BACKGROUND: Freehand single photon emission computed tomography (fSPECT) is a three-dimensional (3-D) tomographic imaging modality based on data acquisition with a handheld detector that is moved freely, in contrast to conventional, gantry-mounted gamma camera systems. In this pilot study, we evaluated the feasibility of fSPECT for intraoperative 3-D mapping in patients with parathyroid adenomas. METHODS: Three patients (range 30 to 45 years) diagnosed with hyperparathyroidism (one primary and two tertiary) underwent parathyroid scintigraphy with technetium-99m sestamibi (99mTc-MIBI) to localize parathyroid adenomas. Two patients were referred with persistent hyperparathyroidism after conventional parathyroidectomy. In all three patients, a planar scintigraphy of the neck was performed 10 min after injection (p.i.) followed by SPECT/CT (Symbia T2, Siemens Healthcare) and a correlative ultrasound 2 h p.i. 99mTc-MIBI scan was performed the day before surgery in two patients and at the same day in one patient. fSPECT images were acquired intraoperatively using declipse SPECT (SurgicEyeTM). RESULTS: A total of five parathyroid adenomas were successfully located with SPECT/CT. fSPECT allowed intraoperative detection of all adenomas, and successful parathyroidectomy was accomplished. Parathyroid hormone level decreased intraoperatively in all three patients, on average, by 79% (range 72% to 91%). CONCLUSION: In this preliminary study, we could demonstrate that intraoperative localization of parathyroid adenomas is feasible using the freehand SPECT technology, thus allowing an image-guided parathyroidectomy.

5.
Dtsch Arztebl Int ; 108(20): 341-6, 2011 May.
Article in English | MEDLINE | ID: mdl-21655459

ABSTRACT

BACKGROUND: Bariatric surgery has increased in numbers, but the treatment of morbid obesity in Germany still needs improvement. The new interdisciplinary S3-guideline provides information on the appropriate indications, procedures, techniques, and follow-up care. METHODS: Systematic review of the literature, classification of the evidence, graded recommendations, and interdisciplinary consensus-building. RESULTS: Bariatric surgery is a component of the multimodal treatment of obesity, which consists of multidisciplinary evaluation and diagnosis, conservative and surgical treatments, and lifelong follow-up care. The current guideline extends the BMI-based spectrum of indications that was previously proposed (BMI greater than 40 kg/m(2), or greater than 35 kg/m(2)with secondary diseases) by eliminating age limits, as well as most of the contraindications. A prerequisite for surgery is that a structured, conservative weight-loss program has failed or is considered to be futile. Type 2 diabetes is now considered an independent indication under clinical study conditions for patients whose BMI is less than 35 kg/m(2) (metabolic surgery). The standard laparoscopic techniques are gastric banding, gastric bypass, sleeve gastrectomy, and biliopancreatic diversion. The choice of procedure is based on knowledge of the results, long-term effects, complications, and individual circumstances. Structured lifelong follow-up should be provided and should, in particular, prevent metabolic deficiencies. CONCLUSION: The guideline contains recommendations based on the scientific evidence and on a consensus of experts from multiple disciplines about the indications for bariatric surgery, the choice of procedure, techniques, and follow-up care. It should be broadly implemented to improve patient care in this field.


Subject(s)
Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Foreign-Body Migration/etiology , Hernia, Abdominal/etiology , Malabsorption Syndromes/etiology , Obesity, Morbid/surgery , Foreign-Body Migration/diagnostic imaging , Hernia, Abdominal/diagnostic imaging , Humans , Malabsorption Syndromes/diagnostic imaging , Radiography
6.
Int J Colorectal Dis ; 26(4): 397-404, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21318299

ABSTRACT

BACKGROUND: The young field of obesity surgery (bariatric surgery) in Germany expands as a consequence of the rapid increase of overweight and obesity. New surgical methods, minimal access techniques, and the enormous increase of scientific studies and evidence, all contribute to the success of bariatric surgery, which is the only realistic chance of permanent weight loss and regression of secondary diseases in many cases. METHODS: A systematic literature review, classification of evidence, graded recommendations, and interdisciplinary consensus. RESULTS: Obesity surgery is an integral component of the multimodal treatment of obesity, which consists of multidisciplinary evaluation and preparation, conservative and surgical treatment elements, and a life-long follow-up. The guideline confirms the body mass index (BMI)-based spectrum of indications (BMI > 40 kg/m(2) or >35 kg/m(2) with secondary diseases) and extends it through elimination of all age restrictions (>18 years and <60 years) and most of the contraindications. Precondition for surgery is the failure of a structured conservative program of 6-12 months or the expected futility of it. Type II diabetes mellitus becomes an independent indication criterion for BMI < 35 kg/m(2) (metabolic surgery). The standard techniques are gastric balloon, gastric banding, gastric bypass, gastric sleeve, and biliopancreatic diversion. The choice of procedure is based on profound knowledge of results, long-term effects, complications, and patient-specific circumstances. The after-care should be structured and organized long term. CONCLUSION: The S3-guidelines contain evidence-based recommendations for the indication, selection of procedure, technique, and follow-up. Patient care should improve after implementation of these guidelines in clinical practice. Compliance by decision makers and health insurers is warranted.


Subject(s)
Bariatric Surgery , Evidence-Based Medicine , Obesity/surgery , Germany , Humans , Postoperative Care , Time Factors
7.
J Surg Res ; 169(2): 241-6, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20080250

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) have gained attention as an epigenetic component involved in the development of pancreatic ductal adenocarcinoma (PDAC). Several methods for miRNA profiling are in common use, but the validity of these methods is not defined. The aim of this study was to define the optimal method for miRNA detection in PDAC. METHODS: miRNA expression was determined using different and partially redundant methods (miRNA microarray, TaqMan low density array (TLDA), single tube quantitative RT-PCR). The data from different methods were statistically evaluated and tested for intermethodic consistency and reliability of the results. Finally, the miRNA expression status and the cell lines' ability to metastasize were correlated. RESULTS: Comparing low and high metastatic cells, miRNA-microarrays identified fewer differentially expressed and only upregulated miRNAs (n=27; 27 up-regulated) compared with TLDAs (n=54; 19 up- and 35 down-regulated). Evaluating miRNAs that target tumor suppressor genes, expression of all single tube quantitative real-time reverse transcriptase PCR (qRT-PCR) validated miRNAs was detected to be significantly altered in TLDA analysis (100%). MiRNA microarrays detected only 25% of qRT-PCR validated miRNAs. Furthermore, results from TLDA analysis correlated well with data from qRT-PCR and presented ΔΔCt values from 3.5±1.86 (range 0.8-5.62) compared with 3.74±1.86 (range 0.78-5.95) in qRT-PCR. CONCLUSION: Notable differences comparing data obtained from different screening methods were found. While TLDA and qRT-PCR correlated well in quantity and quality of the measured miRNAs, several tumor suppressor gene targeting and down-regulated miRNAs were not detected by miRNA-microarrays. This heterogeneity shows that care must be exercised when comparing results from different methods in PDAC.


Subject(s)
Adenocarcinoma/metabolism , Carcinoma, Pancreatic Ductal/metabolism , MicroRNAs/metabolism , Pancreatic Neoplasms/metabolism , Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Epigenesis, Genetic , Gene Expression Profiling , Humans , Microarray Analysis , Pancreatic Neoplasms/pathology , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction
8.
J Surg Res ; 171(1): 136-42, 2011 Nov.
Article in English | MEDLINE | ID: mdl-20605603

ABSTRACT

OBJECTIVES: The microenvironment is known to be a relevant factor of influence on tumor growth and metastasis in pancreatic ductal adenocarcinoma (PDAC). To determine the influence of the microenvironment on changes in gene expression, we analyzed gene expression in different PDAC tissues. METHODS: Four human PDAC cell lines were introduced into a murine PDAC model with two insertion techniques: injection and implantation. Gene expression profiles of the cell lines growing in vitro and in vivo (ectopically and orthotopically) were established by microarray and validated by RT-PCR. RESULTS: Significant differences were found in the gene expression profiles of the in vitro versus in vivo tissues (P < 0.05), while no differences were found between the in vivo tissues. Analyzing the orthotopic tumors derived from the injection and implantation methods, similar gene expression patterns with 0%-18% significantly differentially expressed genes between tumors of the two different methods were observed (analysis of variance [ANOVA]; P < 0.0001). CONCLUSIONS: Gene expression from cell lines growing in vitro differed from the expression patterns of the same cells growing in vivo, while the localization of the growing tumor cells did not significantly alter gene expression. These data demonstrate that the implantation and injection techniques used in this study yield similar results and may be compared with each other.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Pancreatic Ductal/genetics , Gene Expression Regulation, Neoplastic/physiology , Pancreatic Neoplasms/genetics , Tumor Microenvironment/genetics , Adenocarcinoma/physiopathology , Animals , Carcinoma, Pancreatic Ductal/physiopathology , Cell Line, Tumor , Disease Models, Animal , Gene Expression Profiling , Humans , Male , Mice , Mice, Nude , Neoplasm Transplantation/methods , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/physiopathology
9.
Surg Today ; 40(12): 1123-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21110154

ABSTRACT

PURPOSE: Serum calcium has been suggested to be a surrogate marker for intraoperative monitoring during a parathyroidectomy (PTX) for primary hyperparathyroidism (pHPT). The objective of the present prospective study was to investigate whether serum calcium can be used as an alternative for parathyroid hormone intraoperative monitoring. METHODS: Intact parathyroid hormone (iPTH), total and ionized serum calcium, total protein (tP), and pH were monitored in parallel in 25 patients during a successful directed PTX for pHPT. RESULTS: All patients had at least a 50% decrease of iPTH 10 min after PTX. Simultaneously measured total serum calcium (tCa) and ionized serum calcium (iCa) did not correlate with iPTH or pH. However, tCa and iCa levels correlated with changes in tP (r = 0.859; P < 0.001; r = 0.483; P = 0.014). In addition, intraoperative iCa changes correlated with preoperative iCa levels (r = -0.475, P = 0.016). A linear regression analysis for parameters potentially influencing intraoperative tCa and iCa dynamics changes identified tP changes as the only parameter influencing tCa and iCa changes (P < 0.001). CONCLUSION: Individual short-term intraoperative changes of tCa or iCa are not predictive for successful PTX, as they more likely reflect changes in intraoperative fluid management rather than decreased iPTH.


Subject(s)
Calcium/blood , Hyperparathyroidism, Primary/surgery , Monitoring, Intraoperative/methods , Parathyroidectomy , Adult , Aged , Aged, 80 and over , Female , Humans , Linear Models , Male , Middle Aged , Parathyroid Hormone/blood , Predictive Value of Tests , Prospective Studies , Treatment Outcome
10.
Int J Cancer ; 126(1): 114-24, 2010 Jan 01.
Article in English | MEDLINE | ID: mdl-19569050

ABSTRACT

Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiled via mRNA-microarray as well as Taqman Low Density Array, and validated by single quantitative RT-PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR-194 (fold change: 26.88), miR-200b (fold change: 61.65), miR-200c (fold change: 19.44) and miR-429 (fold change: 21.67) (p < 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p < 0.0001) and protein (p < 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR-194, miR-200b, miR-200c and miR-429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis-specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal/genetics , E1A-Associated p300 Protein/genetics , MicroRNAs/genetics , Neoplasm Metastasis/genetics , Pancreatic Neoplasms/genetics , Animals , Blotting, Western , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Gene Expression Profiling , Humans , Male , Mice , Mice, Nude , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction
11.
Ann Surg Oncol ; 16(8): 2339-50, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19475450

ABSTRACT

BACKGROUND: Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas. METHODS: A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low-density array. Quantitative real-time-polymerase chain reaction and flow cytometry were used for expression validation. RESULTS: CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40-related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01). CONCLUSIONS: Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC.


Subject(s)
Adenocarcinoma/genetics , CD40 Antigens/genetics , Carcinoma, Pancreatic Ductal/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Pancreatic Neoplasms/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , CD40 Antigens/metabolism , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Disease Progression , Flow Cytometry , Gene Expression Profiling , Humans , Male , Mice , Mice, Nude , MicroRNAs/metabolism , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
12.
Dis Colon Rectum ; 51(11): 1681-5, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18484137

ABSTRACT

PURPOSE: Treatment options for anal and perianal warts caused by human papillomavirus include topical application of cytotoxic substances or immunomodulators and ablative procedures. The objective of this prospective study was the evaluation of the ultrasound-driven Harmonic Scalpel (Ethicon Endo-Surgery, Norderstedt, Germany) for resection of anal and perianal condylomata acuminata. METHODS: Eight men and three women (age range, 26-72 years) with anal and perianal condylomata acuminata were treated by a Harmonic Scalpel blade operating at a vibration frequency of 55.5 kHz and within a temperature range of 65 degrees C to 120 degrees C. Nine patients were treatment naïve, and two patients had recurrent disease. Follow-up ranged from 4 to 26 months. RESULTS: Seven patients had perianal condylomata, two patients had exclusively intra-anal, and two patients had perianal and intra-anal warts. All condylomata were excised in a single-step procedure with complete clearing without injury of subepidermal layers. We observed no intraoperative or postoperative complications. No recurrences occurred during follow-up. CONCLUSIONS: The Harmonic Scalpel has been an effective and safe method for the treatment of anal perianal human papillomavirus condylomata without recurrent warts. Subepidermal skin levels remained uninjured; thus, no complications or unsatisfactory cosmesis occurred.


Subject(s)
Anus Diseases/therapy , Cautery/instrumentation , Condylomata Acuminata/therapy , Ultrasonic Therapy/instrumentation , Adult , Aged , Anus Diseases/pathology , Condylomata Acuminata/pathology , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Treatment Outcome
13.
Eur J Endocrinol ; 158(6): 811-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18322301

ABSTRACT

CONTEXT: For rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify the RET mutation into one of the three clinical risk groups. OBJECTIVE: We analyzed proliferative properties and clinical implications associated with the RET protooncogene transmembrane domain mutation S649L. DESIGN: The transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation. PATIENTS: Fifteen individuals from five kindreds were identified as carriers of a RET protooncogene mutation in exon 11 codon 649 (TCG(Ser)-->TTG(Leu)). In two out of five index patients, a second RET mutation (C634W or V804L) was detected. RESULTS: Eight gene carriers were operated on. Histology revealed MTC and C-cell hyperplasia in three index and three screening patients respectively. In all other gene carriers (aged 41-64 years), calcitonin levels were in the normal range, and pentagastrin-stimulated calcitonin levels were <100 pg/ml. Therefore, thyroidectomy had not yet been performed. In one index patient carrying the S649L mutation, hyperparathyroidism was confirmed histologically. RET S649L-expressing NIH3T3 cells exhibited a clear increase of phosphotyrosine and proliferation rate when compared with parental NIH3T3 cells but a significantly lower kinase activity and cell growth rate when compared with RET C634R-expressing cells. When compared with RET C634R, the S649L mutant showed moderate transforming potential with small-sized colonies. CONCLUSIONS: Our clinical and in vitro findings indicate that the transmembrane RET S649L mutation is associated with late-onset non-aggressive disease. Recommendations for prophylactic thyroidectomy should be individualized depending on stimulated calcitonin levels.


Subject(s)
Carcinoma, Medullary/genetics , Mutation , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Adult , Amino Acid Substitution , Animals , Binding Sites/genetics , Carcinoma, Medullary/pathology , Cell Proliferation , Cell Survival/genetics , Cell Survival/physiology , Female , Genotype , Humans , Male , Mice , Middle Aged , NIH 3T3 Cells , Pedigree , Proto-Oncogene Proteins c-ret/metabolism , Proto-Oncogene Proteins c-ret/physiology , Thyroid Neoplasms/pathology
14.
Cancer Biol Ther ; 6(11): 1700-3, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17986871

ABSTRACT

Renal cell carcinoma (RCC) occurring in renal allografts after cadaveric kidney transplantation has rarely been observed. RCC accounts for 2.3% of all malignancies in the general population, but up to 4.8% of malignancies in renal transplant recipients. Most have been reported in the patient's own diseased kidneys, whereas RCC in the renal allograft occur in only 10%. Here, we describe an organ-preserving surgical technique of a malignant renal tumor in a kidney allograft using a harmonic scalpel (Ultracision) for tumor enucleation. Furthermore we demonstrate by DNA microsatellite analysis the tumor's genetic origin as donor related. Collectively, we suggest that patients with a well defined low grade RCC in the kidney allograft and altogether low malignancy and good allograft function should only undergo an organ-preserving procedure and short-term postoperative screening.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Kidney Transplantation , Nephrons/surgery , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Magnetic Resonance Imaging , Microsatellite Repeats , Middle Aged , Transplantation, Homologous
15.
Langenbecks Arch Surg ; 392(2): 135-41, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17216285

ABSTRACT

BACKGROUND AND AIMS: Controversy still exists about the need for pyloric drainage procedures (pyloroplasty or pyloromyotomy) after esophagectomy with esophagogastrostomy and vagotomy. Although pyloric drainage may prevent postoperative delayed gastric emptying, it may also promote bile reflux into the oesophagus. We analysed pyloric drainage methods for their potential effect on gastric outlet obstruction and bile reflux in patients undergoing esophagectomy. MATERIALS AND METHODS: One hundred and ninety-eight patients with esophageal carcinoma were treated by transthoracal esophagectomy with gastric conduit reconstruction either with pyloromyotomy (group II, n = 118), pyloroplasty (group III, n = 34) or without pyloric drainage (group I, n = 46) between January 2000 and December 2004. The postoperative gastrointestinal passage by radiological investigation, anastomotic leakage rate, mortality and incidence of gastroesophageal reflux by endoscopy within the first postoperative year were retrospectively analysed. RESULTS: Patient demographics and the types of surgical procedures did not differ between the three groups. There was no difference in hospital mortality, anastomotic leakage rate, gastrointestinal passage and postoperative hospital stay between the three groups. However, more patients with pyloric drainage showed bile reflux (I = 0% vs II+III=14.9%, p = 0.069) and reflux esophagitis (I = 10.3% vs II+III = 34.5%, p < 0.05) compared to patients without pyloric drainage. On the multivariate analysis, pyloric drainage and the anastomotic height were independent and were significant risk factors associated with postoperative reflux esophagitis. CONCLUSION: Pyloric drainage after esophagectomy with gastric conduit reconstruction should be omitted because it does not improve gastric emptying and may favour biliary reflux esophagitis.


Subject(s)
Drainage , Esophageal Neoplasms/surgery , Esophagectomy , Pylorus/surgery , Stomach/transplantation , Aged , Anastomosis, Surgical , Deglutition Disorders/epidemiology , Drainage/methods , Esophagectomy/adverse effects , Female , Gastric Emptying , Gastric Outlet Obstruction , Gastroesophageal Reflux/epidemiology , Heartburn/epidemiology , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Plastic Surgery Procedures , Vagotomy
16.
Ann Surg Oncol ; 14(4): 1327-35, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17235717

ABSTRACT

BACKGROUND: The objective of this study was to identify genomic alterations in resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with histopathological and clinical data to verify their prognostic significance. METHODS: Specimens of 33 PCA were investigated by comparative genomic hybridization. Microdissection was used for separation of PCA from the normal cells before isolation of DNA; nick-end labeling and hybridization were performed according to standard protocols. Aberrations were correlated with staging and grading using log-rank test and Cox regression. Survival rates were plotted using the Kaplan-Meier method. RESULTS: Twenty-eight (85%) PCA showed aberrations. Gains of chromosomal material were most frequently identified on 8q (42%), 13q (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P < 0.05). Median survival time of all patients was 13 months. Median survival time of patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in patients without gain of 8q (n = 19; P = 0.029). CONCLUSIONS: The chromosomal regions containing genetic alterations represent potential loci for new target genes in PCA. The significant correlation of gain of chromosome 8q with short survival time suggests that 8q may be a new marker to assess prognosis and malignant potential of resected PCA in the individual patient, thereby helping to identify patients at risk for recurrence that might profit from adjuvant therapy.


Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Chromosomes, Human, Pair 8/genetics , Gene Amplification , Pancreatic Neoplasms/genetics , Adenocarcinoma, Mucinous/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/genetics , Chromosome Aberrations , DNA/metabolism , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Nucleic Acid Hybridization , Prognosis , Survival Rate
18.
19.
Int J Cancer ; 110(6): 902-6, 2004 Jul 20.
Article in English | MEDLINE | ID: mdl-15170674

ABSTRACT

Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.


Subject(s)
Genetic Predisposition to Disease/genetics , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Adult , Aged , Family , Female , Germany/epidemiology , Humans , Male , Medical Records , Middle Aged , Odds Ratio , Pancreatic Neoplasms/pathology , Prevalence , Retrospective Studies
20.
J Am Coll Surg ; 196(3): 370-7; discussion 377; author reply 378, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12648686

ABSTRACT

BACKGROUND: Transection of the cricopharyngeus muscle supposedly is of crucial therapeutic importance, because of its hypothesized pathogenic role in Zenker's diverticulum (ZD). This retrospective, nonrandomized study evaluates the outcomes of surgical therapy, with reference to cricopharyngeal myotomy (CM). STUDY DESIGN: Seventy-nine patients underwent diverticulectomy from 1985 to 1999. Group A (n = 47; men:women, 29:18; mean age +/- SD: 69 +/- 12 [range 35 to 87] years) underwent CM because of clearly discernible hypertrophic transverse fibers. In group B (n = 32; men:women, 22:10; mean age +/- SD 68 +/- 13 [range 36 to 95] years), without such transverse fibers, no CM was carried out. Dysphagia, regurgitation, and diverticular radiomorphology were classified according to ordinal scales. Diverticular volumes were calculated from barium swallows. Postoperative symptoms and outcomes were evaluated by questionnaires sent to the patients. RESULTS: The two groups did not differ significantly in severity of preoperative dysphagia and regurgitation, radiomorphology, or median diverticular volume. Both groups experienced postoperative alleviation of symptoms (p < 0.001), persisting slightly in 11 of 47 (23%) group A and 4 of 32 (13%) group B patients (p > 0.05). Of these, seven group A (64%) patients and three group B patients (75%) had additional upper gastrointestinal tract (GIT) diseases. Recurrent diverticula occurred in one patient and postoperative complications in five patients per group (p > 0.05). Diverticular volume and upper GIT comorbidities, but not CM, were significant risk factors for persistent symptoms in the multivariate analysis. CONCLUSIONS: CM has no significant influence on postoperative results, if carried out depending on the anatomic state and configuration of the cricopharyngeus muscle. This is suggested by the favorable outcomes of patients, with persistent symptoms being caused by factors other than CM.


Subject(s)
Pharyngeal Muscles/surgery , Zenker Diverticulum/surgery , Adult , Aged , Aged, 80 and over , Cricoid Cartilage , Deglutition Disorders/etiology , Female , Gastroesophageal Reflux/etiology , Humans , Logistic Models , Male , Middle Aged , Recurrence , Retrospective Studies , Treatment Outcome
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