Loop Ileostomy Closure: Comparison of Cost Effectiveness between Suture and Stapler

Background: Closure of loop ileostomy can be safely performed using sutures or staplers. The aim of the present study was to compare the cost effectiveness of three different techniques. Methods: A total of 128 consecutive patients who underwent closure of loop ileostomy between January 2002 and December 2008 were analyzed retrospectively. The primary outcome parameter was operative cost. Results: Closure of ileostomy was performed in 66 patients with hand-sewn anastomosis, in 25 patients with stapler only, and in 37 patients with a combination of stapler and suture. There were no differences in terms of early and late postoperative complications. Operative time was significantly longer for "suture only” (101.4±26min) than for "stapler/suture” (−4.9min) and "stapler only” (−17.8min); the difference between the three groups is significant (p=0.05). Duration of hospital stay was not different among the three groups. Operative costs with "stapler/suture” (1,755.9±355.6 EUR) were significantly higher than with "suture only” (−254 EUR; p=0.001) and "stapler only” (−236 EUR; p=0.005). Conclusions: Operative time using the stapler only is significantly shorter than with hand-sewn anastomosis or combinations of stapler and suture. Operative costs are significantly higher for a procedure that includes suture and staple

Hereditäre gastrointestinale Tumoren

Eine familiäre Veranlagung liegt in einem Viertel aller Fälle von kolorektalen Karzinomen vor. Sehr viel weniger Patienten (ca. 5 %) sind von einer vererbbaren genetischen Veranlagung betroffen. Dabei ist es interessant, dass ein nennenswerter Prozentsatz der hereditären Tumoren durch Neumutationen verursacht wird – die Familiengeschichte ergibt also keinen Hinweis, die Diagnose ist aber wichtig für die PatientInnen und ihre Nachkommen. Verbesserte Diagnostik führt dazu, dass der Anteil hereditärer Ursachen bei den kolorektalen Karzinomerkrankungen zunimmt und wohl noch weiter zunehmen wird. Das insgesamt verbesserte Überleben onkologischer Patienten wiederum führt dazu, dass auch häufiger Patienten mit Zweit- oder Drittkarzinomen behandelt werden. Aber zu häufig noch werden Patienten tatsächlich erst bei einem zweiten oder dritten Karzinom der entsprechenden Diagnostik zugeführt. Es sollen in diesem Artikel die häufigsten polypösen und nichtpolypösen kolorektalen hereditären Tumorerkrankungen, die dazugehörigen Surveillance-Programme und Operationsmethoden vorgestellt werden. Ebenso wird aufgezeigt, welche anderen Organe betroffen sein können. = Une prédisposition familiale est présente dans un quart de tous les cancers colorectaux. Beaucoup moins de patients (~ 5 %) sont touchés par une prédisposition génétique héréditaire. Dans ce contexte, il est intéressant qu’un pourcentage important de tumeurs héréditaires est dû à de nouvelles mutations; les antécédents familiaux ne fournissent alors aucun indice, mais le diagnostic est important pour les patients et patientes ainsi que pour leurs descendants. Lʼamélioration des méthodes de diagnostic signifie que la proportion de causes héréditaires des cancers colorectaux augmente et continuera sans doute à augmenter. La survie globalement accrue des patients oncologiques signifie à son tour que plus souvent les patients atteints d’un deuxième ou troisième cancer sont également traités. Mais il arrive encore trop souvent que des patients ne soient effectivement diagnostiqués correctement que lors d’un deuxième ou troisième cancer. Cet article entend présenter les tumeurs colorectales héréditaires polypeuses et non polypeuses les plus fréquentes ainsi que les programmes de surveillance correspondants et les méthodes chirurgicales. Il montre aussi quels autres organes peuvent être affectés. = Un quarto dei casi di carcinoma colorettale è associato a una predisposizione familiare. Molti meno pazienti (circa il 5 %) sono affetti da una predisposizione genetica ereditaria. È interessante notare che una percentuale significativa di tumori ereditari è causata da nuove mutazioni – la storia familiare non fornisce dunque alcun indizio, la diagnosi è tuttavia importante per i pazienti e i loro discendenti. Grazie a una diagnostica più accurata la percentuale delle cause ereditarie del carcinoma colorettale è in aumento e probabilmente continuerà ad aumentare in futuro. D’altra parte, il miglioramento complessivo della sopravvivenza dei pazienti oncologici comporta anche una maggiore frequenza delle cure rivolte a pazienti con un secondo o un terzo carcinoma. Troppo spesso tuttavia i pazienti vengono indirizzati verso la diagnosi appropriata solo dopo un secondo o un terzo carcinoma. In questo articolo saranno presentate le più comuni malattie tumorali ereditarie poliposiche e non poliposiche insieme ai relativi programmi di sorveglianza e ai metodi chirurgici. Saranno anche indicati gli altri organi che possono essere colpiti

Kidney Retransplantation after Graft Failure: Variables Influencing Long-Term Survival

Background: There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective: To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan-Meier method, and risk factors were identified using multiple Cox regression. Results: We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, p=0.104) but an inferior graft survival thereafter (log-rank p=0.026). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson-Deyo index, active smoking, and life-threatening complications (Clavien-Dindo grade IV) at first transplantation. Conclusion: Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible

Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods: We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results: Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions: Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.publishedVersionPeer reviewe

Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an “average sex “or a pathogenic variant in an “average Lynch syndrome gene” and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host’s adaptive immune system’s ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer