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1.
Digestion ; 104(5): 391-399, 2023.
Article in English | MEDLINE | ID: mdl-37331350

ABSTRACT

INTRODUCTION: Cold snare polypectomy (CSP) is a safe and effective procedure for small colorectal polyps ≤9 mm. There are only limited data regarding CSP of larger neoplastic lesions. This study evaluated the efficacy and safety of CSP for polyps between 10 and 15 mm in size. METHODS: In this prospective single-arm observational pilot study, patients with a least one polyp 10-15 mm were included. These polyps were preferably removed by CSP using a dedicated hybrid snare. The primary outcome was the histological complete resection rate (CRR) determined by pathologically negative margins of the specimen and no neoplastic tissue obtained from biopsies of the resection site margin. Secondary outcomes were en bloc resection rate, failure of CSP, and incidence of adverse events. RESULTS: A total of 61 neoplastic polyps were removed from 39 patients. Overall CRR was 80.3% (49/61). CSP was feasible in 78.7% (48/61) of polyps and the CRR in this group was 85.4% (41/48). When CSP failed (13/61; 21.3%), lesions were successfully resected by immediate HSP using the same snare with a CRR of 61.5% (8/13) in this group. One patient presented delayed hemorrhage after HSP of a polyp but successful hemostasis was achieved with two hemoclips. No other adverse events occurred. No recurrence was seen on follow-up colonoscopy in cases with incomplete resected polyps. CONCLUSION: CSP seems to be efficient and safe in removing colorectal polyps up to 15 mm. A hybrid snare seems to be particularly advantageous for these polyps as it allows immediate conversion to HSP if CSP might fail in larger polyps. This trial is registered at ClinicalTrials.gov (NCT04464837).


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Humans , Colonoscopy/adverse effects , Colonoscopy/methods , Colonic Polyps/surgery , Colonic Polyps/pathology , Prospective Studies , Pilot Projects , Treatment Outcome , Margins of Excision , Colorectal Neoplasms/pathology
2.
Front Surg ; 10: 1099457, 2023.
Article in English | MEDLINE | ID: mdl-37143771

ABSTRACT

Background and study aim: Endoscopic negative pressure therapy (ENPT) is well established in the treatment of perforations of various etiologies in the upper and lower gastrointestinal tract. For duodenal perforations exist only case reports and series. Different indications are possible for ENPT in duodenal position: primary therapy for leaks, preemptive therapy after surgery for example, after ulcer suturing or resection with anastomoses, or as second line therapy in cases of recurrent anastomotic insufficiencies with leakage of duodenal secretion. Methods: A retrospective 4-year case series of negative pressure therapy in duodenal position indicated by different etiologies and a comprehensive review of current literature on endoscopic negative pressure duodenal therapy are presented. Results: Patients with primary duodenal leaks n= 6 and with duodenal stump insufficiencies n = 4 were included. In seven patients ENPT was the first line and sole therapy. Primary surgery for duodenal leak was performed in n = 3 patients. Mean duration of ENPT was 11.0 days, mean hospital stay was 30.0 days. Re-operation after start of ENPT was necessary in two patients with duodenal stump insufficiencies. Surgery after termination of the ENPT was not necessary in any patient. Discussion: In our case series and in the literature, ENPT has been shown to be very successful in the therapy of duodenal leaks. A challenge in ENPT for duodenal leaks is the appropriate length of the probe to safely reach the leak and keep the open pore element at the end of the probe in place despite intestinal motility.

3.
World J Gastrointest Surg ; 14(8): 799-808, 2022 Aug 27.
Article in English | MEDLINE | ID: mdl-36157364

ABSTRACT

BACKGROUND: Endoscopic treatment of pancreatic necrosis can be challenging and time-consuming because sticky necrotic debris is sometimes difficult to remove. The over-the-scope-grasper, a new tool that has recently become available for this purpose, might also be useful for other indications. However, clinical data on the efficacy and safety of this new device are lacking. AIM: To evaluate the technical success and safety of the device in a multicenter setting. METHODS: The over-the-scope-grasper was used in nine selected endoscopic centers between November 2020 and October 2021 for appropriate indications. Overall, 56 procedures were included in the study. We retrospectively evaluated procedural parameters of all endoscopic interventions using a predefined questionnaire, with special respect to technical success, indications, duration of intervention, type of sedation, and complications. In the case of pancreatic necrosectomy, the access route, stent type, number of necrosis pieces removed, and clinical handling were also recorded. RESULTS: A total of 56 procedures were performed, with an overall technical success rate of 98%. Most of the procedures were endoscopic pancreatic necrosectomies (33 transgastric, 4 transduodenal). In 70% of the procedures, access to the necrotic cavity was established with a lumen apposing metal stent. The technical success of pancreatic necrosectomy was 97%, with a mean of 8 pieces (range, 2-25 pieces) of necrosis removed in a mean procedure time of 59 min (range, 15-120 min). In addition, the device has been used to remove blood clots (n = 6), to clear insufficiency cavities before endoluminal vacuum therapy (n = 5), and to remove foreign bodies from the upper gastrointestinal tract (n = 8). In these cases, the technical success rate was 100%. No moderate or severe/fatal complications were reported in any of the 56 procedures. CONCLUSION: These first multicenter data demonstrate that the over-the-scope-grasper is a promising device for endoscopic pancreatic necrosectomy, which is also appropriate for removing foreign bodies and blood clots, or cleaning insufficiency cavities prior to endoluminal vacuum therapy.

4.
World J Surg Oncol ; 20(1): 104, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35354483

ABSTRACT

BACKGROUND: Malignant tumors of the esophagus are the sixth leading cause of cancer-related deaths worldwide. Postoperative leakage of the esophago-gastrostomy leads to mediastinal sepsis, which is still associated with a high morbidity and mortality rate. The aim of this study was to describe the endoscopic view of the different severity grades of an anastomotic leakage. METHODS: Patients Between June 2016 and September 2018, 144 patients were operated upon in the Department of Surgery, University of Munich, Germany. Among these patients, 34 (23.6%) presented with a leakage of the anastomosis. Endoscopy In this retrospective analysis, the focus is to describe different patterns of leakage of the anastomosis. RESULTS: We studied 34 patients in whom post-esophagectomy leakage of the anastomosis was detected and treated with an endoluminal vacuum sponge system. The leakage healed in 26 of 29 patients (success rate 89.7%). With the increasing severity of leakage, the treatment time and the in-hospital mortality correspondingly increased. Furthermore, the incidence of the development of a fistula to the tracheobronchial system increased with higher grades of leakage. CONCLUSIONS: Exact descriptions of leakage are necessary to compare the cases and to prove post-treatment improvement. This is, to our knowledge, the first publication to present a leakage grading score in patients after esophagectomy including reconstruction with a gastric tube. This new grading system needs to be tested in further analyses, with a special focus on prospective analysis.


Subject(s)
Anastomotic Leak , Esophagus , Anastomotic Leak/etiology , Endoscopy, Gastrointestinal , Esophagectomy/adverse effects , Esophagus/surgery , Humans , Retrospective Studies
5.
Sci Rep ; 11(1): 18370, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34526594

ABSTRACT

Endoscopic ultrasonography (EUS) is a safe, real-time diagnostic and therapeutic tool. Speckle noise, inherent to ultrasonography, degrades the diagnostic precision of EUS. Elevational angular compounding (EAC) can provide real-time speckle noise reduction; however, EAC has never been applied to EUS because current implementations require costly and bulky arrays and are incompatible with the tight spatial constraints of hollow organs. Here we develop a radial implementation of a refraction-based elevational angular compounding technique (REACT) for EUS and demonstrate for the first time spatial compounding in a radial endoscopy. The proposed implementation was investigated in cylindrical phantoms and demonstrated superior suppression of ultrasound speckle noise and up to a two-fold improvement in signal- and contrast- ratios, compared to standard image processing techniques and averaging. The effect of elevational angular deflection on image fidelity was further investigated in a phantom with lymph node-like structures to determine the optimum elevational angular width for high speckle reduction efficiency while maintaining image fidelity. This study introduces REACT as a potential compact and low-cost solution to impart current radial echo-endoscopes with spatial compounding, which could enable accurate identification and precise sizing of lymph nodes in staging of gastrointestinal tract cancers.

6.
Nutr Cancer ; 69(1): 84-91, 2017 01.
Article in English | MEDLINE | ID: mdl-27897439

ABSTRACT

BACKGROUND: Interleukin-4 (IL-4) together with interleukin-13 (IL-13) play an important role in inflammation and wound repair, and are known to be upregulated in human skeletal muscle after strenuous physical exercise. Additionally, these cytokines may act as autocrine growth factors in pancreatic cancer cells. We hypothesize that IL-4, IL-13, and their corresponding receptors are involved in mechanism of cancer cachexia. METHODS: Tissue samples from human skeletal muscle, white fat, liver, healthy pancreas, and pancreatic ductal adenocarcinoma were analyzed by quantitative real-time polymerase chain reaction for mRNA expression levels of IL-4, IL-13, IL-4 receptor α, and IL-13 receptor α1. RESULTS: We demonstrate for the first time that liver IL-4 mRNA is downregulated in vivo in patients with pancreatic cancer and cachexia. Additionally, IL-4 mRNA in the liver inversely correlated with musculus psoas thickness. CONCLUSION: We speculate that suppression of IL-4 is involved in cancer cachexia, although the exact mechanisms have to be further elucidated.


Subject(s)
Cachexia/genetics , Interleukin-4/genetics , Liver/physiology , Pancreatic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Cachexia/etiology , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Interleukin-13/genetics , Interleukin-13 Receptor alpha1 Subunit/genetics , Interleukin-4 Receptor alpha Subunit/genetics , Liver/pathology , Male , Middle Aged , Pancreatic Neoplasms/complications , Real-Time Polymerase Chain Reaction , Retrospective Studies , Pancreatic Neoplasms
7.
BMC Cancer ; 16: 75, 2016 Feb 08.
Article in English | MEDLINE | ID: mdl-26856534

ABSTRACT

BACKGROUND: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. DISCUSSION: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future.


Subject(s)
Cachexia/pathology , Muscle, Skeletal/pathology , Neoplasms/pathology , Animals , Cachexia/complications , Cachexia/metabolism , Disease Models, Animal , Humans , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Neoplasms/complications , Neoplasms/metabolism , Weight Loss
8.
Genomics ; 106(1): 7-14, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25812950

ABSTRACT

UNLABELLED: Pancreatic cancer is one of the most aggressive malignant tumors, mainly due to an aggressive metastasis spreading. In recent years, circulating tumor cells became associated to tumor metastasis. Little is known about their expression profiles. The aim of this study was to develop a complete workflow making it possible to isolate circulating tumor cells from patients with pancreatic cancer and their genetic characterization. RESULTS: We show that the proposed workflow offers a technical sensitivity and specificity high enough to detect and isolate single tumor cells. Moreover our approach makes feasible to genetically characterize single CTCs. CONCLUSIONS: Our work discloses a complete workflow to detect, count and genetically analyze individual CTCs isolated from blood samples. This method has a central impact on the early detection of metastasis development. The combination of cell quantification and genetic analysis provides the clinicians with a powerful tool not available so far.


Subject(s)
Neoplastic Cells, Circulating/metabolism , Pancreatic Neoplasms/genetics , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Separation , Female , Flow Cytometry , Humans , Male , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pilot Projects
9.
Hepatogastroenterology ; 61(133): 1313-20, 2014.
Article in English | MEDLINE | ID: mdl-25436303

ABSTRACT

BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most common malignancies worldwide. The only curative treatment is surgery. As hepatocellular carcinoma is often associated with liver cirrhosis, patients are at risk for postoperative liver failure. In the recent years, platelets are thought to play an important role in liver regeneration.The aim of this study was to discover the relevance of postoperative platelet counts after liver resection for hepatocellular carcinoma. METHODOLOGY: Data of 68 patients who underwent liver resection for hepatocellular carcinoma between July 2007 and July 2012 in a single centre were analysed. Postoperative morbidity and mortality were evaluated in regard to postoperative platelet counts. Comparative analysis between patients with platelet counts ≤100 2x109/ l and >100 x109/ l at d1 was performed in regard to postoperative outcome. RESULTS: Within this cohort, 43 patients (63%) suffered from histologically proven liver cirrhosis. Postoperative mortality was statistically significant associated with postoperative reduced platelet counts. Comparative analysis showed significantly elevated postoperative bilirubin levels and lower prothrombin time in patients with platelet counts ≤ 100 1x109/ l at d1. CONCLUSIONS: Postoperative low platelet counts are associated with poor outcome after hepatic resection for hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Platelet Count , Thrombocytopenia/etiology , Adult , Aged , Aged, 80 and over , Bilirubin/blood , Biomarkers/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy/mortality , Humans , Liver Neoplasms/blood , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Prothrombin Time , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/mortality , Time Factors , Treatment Outcome
10.
World J Gastroenterol ; 20(28): 9361-73, 2014 Jul 28.
Article in English | MEDLINE | ID: mdl-25071331

ABSTRACT

Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients' outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.


Subject(s)
Cachexia/therapy , Carcinoma, Pancreatic Ductal/complications , Nutrition Therapy/methods , Pancreatic Neoplasms/complications , Appetite Stimulants/therapeutic use , Cachexia/diagnosis , Cachexia/etiology , Cachexia/physiopathology , Cachexia/psychology , Combined Modality Therapy , Dietary Supplements , Humans , Nutritional Status , Nutritional Support , Palliative Care , Treatment Outcome
11.
ANZ J Surg ; 84(9): 643-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24456401

ABSTRACT

BACKGROUND: Urinary tract complications are relevant sources of morbidity and mortality after kidney transplantation. Incidence is reported within 3-14% in recent studies. Secondary ureteropyelostomy using the native ureter is a surgical option to treat severe urinary tract complications after kidney transplantation.The aim of this study was to evaluate the outcome after ureteropyelostomy using the native ureter in the management of urinary tract complications after kidney transplantation. METHODS: A single centre, retrospective clinical review of prospectively collected data of all patients who received kidney transplantation or combined kidney-pancreas transplantation between January 2001 and June 2009 was performed. All patients who underwent surgical therapy for urinary tract complications were identified and followed up to evaluate graft function and survival. RESULTS: Six hundred forty-six patients received kidney transplantation or combined kidney/pancreas transplantation. Twenty-six patients (4%) had to undergo re-operation due to severe urinary tract complications after kidney transplantation. Sixteen of the 26 patients (62%) received ureteropyelostomy using the ipsilateral native ureter. This reconstructive operation was successful in 14 of 16 patients (87.5%). Two patients needed to be re-operated for surgical complications. CONCLUSION: Ureteropyelostomy using the native ureter to treat ureter-related urinary tract complications after kidney transplantation can be performed safely and result in good graft and patient survival.


Subject(s)
Kidney Pelvis/surgery , Kidney Transplantation , Postoperative Complications/surgery , Ureter/surgery , Ureteral Diseases/surgery , Vesico-Ureteral Reflux/surgery , Adolescent , Adult , Aged , Anastomosis, Surgical , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Ureteral Diseases/etiology , Vesico-Ureteral Reflux/etiology , Young Adult
12.
J Cell Mol Med ; 18(1): 69-79, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24251822

ABSTRACT

Cachexia presents with ongoing muscle wasting, altering quality of life in cancer patients. Cachexia is a limiting prognostic factor for patient survival and health care costs. Although animal models and human trials have shown mechanisms of motorprotein proteolysis, not much is known about intrinsic changes of muscle functionality in cancer patients suffering from muscle cachexia, and deeper insights into cachexia pathology in humans are needed. To address this question, rectus abdominis muscle samples were collected from several surgical control, non-cachectic and cachectic cancer patients and processed for skinned fibre biomechanics, molecular in vitro motility assays, myosin isoform protein compositions and quantitative ubiquitin polymer protein analysis. In pre-cachectic and cachectic cancer patient samples, maximum force was significantly compromised compared with controls, but showed an unexpected increase in myofibrillar Ca(2+) sensitivity consistent with a shift from slow to fast myosin isoform expression seen in SDS-PAGE analysis and in vitro motility assays. Force deficit was specific for 'cancer', but not linked to presence of cachexia. Interestingly, quantitative ubiquitin immunoassays revealed no major changes in static ubiquitin polymer protein profiles, whether cachexia was present or not and were shown to mirror profiles in control patients. Our study on muscle function in cachectic patients shows that abdominal wall skeletal muscle in cancer cachexia shows signs of weakness that can be partially attributed to intrinsic changes to contractile motorprotein function. On protein levels, static ubiquitin polymeric distributions were unaltered, pointing towards evenly up-regulated ubiquitin protein turnover with respect to ubiquitin conjugation, proteasome degradation and de-ubiquitination.


Subject(s)
Abdominal Muscles/metabolism , Cachexia/metabolism , Colonic Neoplasms/metabolism , Myosins/physiology , Pancreatic Neoplasms/metabolism , Abdominal Muscles/pathology , Abdominal Muscles/physiopathology , Adult , Aged , Aged, 80 and over , Cachexia/etiology , Cachexia/physiopathology , Calcium/physiology , Colonic Neoplasms/complications , Colonic Neoplasms/physiopathology , Female , Humans , In Vitro Techniques , Male , Middle Aged , Muscle Contraction , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/physiopathology , Protein Isoforms/metabolism , Single-Cell Analysis , Ubiquitin/metabolism
13.
J Surg Res ; 186(1): 429-35, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24100055

ABSTRACT

BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. METHOD: We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/µL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.


Subject(s)
Anticoagulants/adverse effects , Heparin/adverse effects , Liver Transplantation , Thrombocytopenia/chemically induced , Adult , Aged , Cohort Studies , End Stage Liver Disease/blood , End Stage Liver Disease/surgery , Female , Humans , Incidence , Male , Middle Aged , Platelet Count , Retrospective Studies , Thrombocytopenia/epidemiology
14.
Nutr Cancer ; 65(6): 827-33, 2013.
Article in English | MEDLINE | ID: mdl-23909726

ABSTRACT

Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PDAC) are the most common diseases of the pancreas. Cachexia-weight loss exceeding 10% of stable body weight-is present in up to 80% of patients with PDAC. Because the mechanisms of cachexia are not well known, this provides a possibility to compare clinical courses of benign and malignant cachexia. In this study, 382 patients-242 with a PDAC stage UICC II/ 140 with CP-were documented regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival. Cachexia was present in 41.4% of CP and 31% of cancer patients. We could demonstrate more pronounced systemic effects of cachexia in patients with PDAC. Weight loss was faster in PDAC patients, the amount of weight loss did not differ significantly between the groups. Cachexia had a significant impact on survival and the postoperative course in patients with PDAC and tumor resection. The development of cachexia is faster in patients with a malignant disease and the systemic effects are more pronounced. Therefore, tumor cachexia should be considered as a different entity than cachexia in benign diseases.


Subject(s)
Cachexia/mortality , Pancreatic Neoplasms/mortality , Pancreatitis, Chronic/mortality , Adult , Aged , Body Mass Index , Cachexia/pathology , Endpoint Determination , Female , Humans , Male , Middle Aged , Morbidity , Nutritional Status , Pancreatic Neoplasms/pathology , Pancreatitis, Chronic/pathology , Postoperative Care , Retrospective Studies , Survival Rate , Weight Gain , Weight Loss
15.
BMC Cancer ; 12: 265, 2012 Jun 21.
Article in English | MEDLINE | ID: mdl-22721276

ABSTRACT

BACKGROUND: Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. EXPERIMENTAL DESIGN: We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. RESULTS: Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. CONCLUSIONS: We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.


Subject(s)
Cachexia/genetics , Early Growth Response Protein 1/metabolism , Gene Expression Profiling , Muscle, Skeletal/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Aged , Biopsy , Early Growth Response Protein 1/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Muscle, Skeletal/metabolism , Reproducibility of Results
17.
BMC Surg ; 12: 2, 2012 Feb 08.
Article in English | MEDLINE | ID: mdl-22316122

ABSTRACT

UNLABELLED: A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582. BACKGROUND: Existing evidence suggests that the transfer of results of randomized controlled trials into clinical practice may be limited. Potential reasons can be attributed to aspects of external validity. The aim of this study is to investigate issues related to the external validity of the INSECT trial. METHODS: All participating surgical departments were categorized and the clinical and baseline characteristics of randomized patients were evaluated. In addition, demographic and clinical data of all screened and randomized patients at the Departments of Surgery in Heidelberg and Erlangen were analyzed. RESULTS: Twenty-five centers enrolled a total of 625 patients. These centers included eight primary, 11 secondary, and six tertiary care centers. The tertiary care centers enrolled the most patients (n = 237, 38%) followed by the primary care centers (n = 199, 32%) and the secondary care centers (n = 189 patients; 30%). The mean number and baseline data of randomized patients did not differ between the three types of care centers (p = 0.09). Overall, the treatment according to protocol was at least 92%. At the Department of Surgery, University of Heidelberg, 307 patients were screened and 60 out of 130 eligible patients were randomized. There were no differences in demographic and clinical baseline data between included and non-included patients. In Erlangen, 351 patients were screened and 57 out of 106 eligible patients randomized. CONCLUSIONS: Results of the INSECT trial are applicable to a broad spectrum of patients treated at different hospital levels.


Subject(s)
Abdominal Wound Closure Techniques/instrumentation , Randomized Controlled Trials as Topic , Sutures , Age Factors , Aged , Bias , Female , Hernia, Abdominal/etiology , Humans , Male , Middle Aged , Multicenter Studies as Topic , Patient Selection , Postoperative Complications , Reproducibility of Results , Sex Factors
18.
BMC Cancer ; 9: 255, 2009 Jul 28.
Article in English | MEDLINE | ID: mdl-19635171

ABSTRACT

BACKGROUND: Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10%--is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. METHODS: In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. RESULTS: Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. CONCLUSION: Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss exceeded 5% there was a significantly reduced resection rate to detect, but the changes were significantly more substantial if weight loss was 10% or more. We propose that a weight loss of 10% be defined as significant in pancreatic cancer.


Subject(s)
Cachexia/etiology , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/metabolism , Lung/physiopathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/metabolism , Aged , Cachexia/metabolism , Cachexia/physiopathology , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/physiopathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/physiopathology
19.
J Gastrointest Surg ; 12(7): 1193-201, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18347879

ABSTRACT

INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries with a poor prognosis (5-year survival rates, 25% in patients after tumor resection with adjuvant treatment; overall, the 5-year survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10-30, 2005). Many patients develop a cachectic status during the progression of the disease, and this syndrome accounts for up to 80% of deaths in patients with advanced pancreatic cancer. Remarkably, there are only a few data available on the impact of cachexia in patients with pancreatic cancer scheduled for tumor resection. MATERIAL AND METHODS: Therefore, in this study, 227 consecutive patients with ductal adenocarcinoma of the pancreas were documented over an 18-month period regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival in a prospectively designed database and followed up. RESULTS: In 40.5% of the patients, cachexia was already present at the time of operation. The cachectic patients did present in a worse nutritional status, represented by lower protein, albumins, and hemoglobin levels. Despite no significant differences in tumor size, lymph node status, and CA19-9 levels, the resection rate in patients with cachexia was reduced (77.8% vs. 48.9%) due to a higher rate of metastatic disease in patients with cachexia. The morbidity and in-hospital mortality revealed no significant difference. However, patients with and without cachexia lost weight after operation, and the weight gain started not until 6 months after operation. The survival in patients with cachexia was significantly reduced in patients undergoing tumor resection as well as in palliative treated patients. CONCLUSION: Cachexia has a significant impact on survival and performance status in palliative patients as well as in patients operated for pancreatic cancer. But tumor-related cachexia is not necessarily dependent on tumor size or load and that metastatic dedifferentiation of the tumor might be a critical step in the development of tumor-associated cachexia.


Subject(s)
Cachexia/etiology , Carcinoma, Pancreatic Ductal/surgery , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Aged , Body Weight , Cachexia/epidemiology , Cachexia/therapy , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/pathology , Female , Follow-Up Studies , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Neoplasm Staging , Nutritional Support/methods , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/pathology , Postoperative Care/methods , Prognosis , Retrospective Studies , Survival Rate
20.
Ann Surg Oncol ; 15(1): 186-92, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17943388

ABSTRACT

BACKGROUND: The value of re-exploration for pancreatic ductal adenocarcinoma after the initial diagnosis of unresectability is unclear. METHODS: In this study, we analyzed 33 patients who were re-explored after an initial diagnosis of unresectability. RESULTS: At the time of reoperation, a resectable tumor was found in 18 patients: therefore, 15 pancreaticoduodenectomies, two total pancreatectomies and one left resection were performed with three vascular resections. Morbidity and mortality rates for the cohort were 6/33 and 1/33, without significant differences between resectable and nonresectable patients. Length of stay, duration of operation, and blood loss were significantly increased in the resection group. Kaplan-Meier survival analysis demonstrated increased median survival for resected patients (1078 days after the initial operation versus 547 days in the group of unresectable patients; p = 0.018). Analysis of the reasons against initial resection showed that, if the patients had been sent to a tertiary referral center for pancreatic surgery, a different decision in favor of resection would probably have been made in 14 out of 33 patients. A review of 10 published reports on reoperation for pancreatic cancer revealed results comparable to our study in terms of low morbidity and mortality as well as a survival benefit. CONCLUSIONS: Reoperation for pancreatic ductal adenocarcinoma that is initially deemed unresectable can be safely performed in a selected group of patients by experienced surgeons, supporting the concept of patient centralization in pancreatic surgery. Resection at the second operation may confer a survival benefit even when the initial findings preclude a potentially curative approach.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Pancreatic Ductal/surgery , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Second-Look Surgery , Adenocarcinoma/pathology , Adult , Aged , Carcinoma, Pancreatic Ductal/pathology , Disease-Free Survival , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Prospective Studies , Reoperation , Retrospective Studies , Survival Rate
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