[Surgical proctology - what is common is common]. / Chirurgische Proktologie ­ was häufig ist, ist häufig.

Surgical proctology - what is common is common Abstract. Proctological diseases are extremely common and are often suppressed or concealed by the patients out of shame and unfortunately mostly neglected by the surgeons. This may have to do with the fact that the genesis of these clinical pictures can be completely different and can range from neurological disorders to embryonic maldevelopment to traumatically caused defects. Probably for this reason, in the past proctology was approached by different disciplines with inconsistent therapeutic approaches and non-standardized methods. However, interdisciplinarity is of utmost importance in this field of medicine. Only through a good interaction of the different disciplines in diagnostics and therapy can the best possible outcome be achieved for our patients. The highest good for the life of those affected and one of the most important factors in therapy is the preservation of continence.

Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo.

Sirtuins (SIRT1-7) are a highly conserved family of NAD(+)-dependent enzymes that control the activity of histone and nonhistone regulatory proteins. SIRT1 is purposed to promote longevity and to suppress the initiation of some cancers. Nevertheless, SIRT1 is reported to function as a tumor suppressor as well as an oncogenic protein. Our data show that compared with normal liver or surrounding tumor tissue, SIRT1 is strongly overexpressed in human hepatocellular carcinoma (HCC). In addition, human HCC cell lines (Hep3B, HepG2, HuH7, HLE, HLF, HepKK1, skHep1) were screened for the expression of the sirtuin family members and only SIRT1 was consistently overexpressed compared with normal hepatocytes. To determine its effect on HCC growth, SIRT1 activity was inhibited either with lentiviruses expressing short hairpin RNAs or with the small molecule inhibitor, cambinol. Knockdown or inhibition of SIRT1 activity had a cytostatic effect, characterized by an altered morphology, impaired proliferation, an increased expression of differentiation markers, and cellular senescence. In an orthotopic xenograft model, knockdown of SIRT1 resulted in 50% fewer animals developing tumors and cambinol treatment resulted in an overall lower tumor burden. Taken together, our data show that inhibition of SIRT1 in HCC cells impairs their proliferation in vitro and tumor formation in vivo. These data suggest that SIRT1 expression positively influences the growth of HCC and support further studies aimed to block its activity alone or in combination as a novel treatment strategy.

Inhibition of SIRT1 impairs the accumulation and transcriptional activity of HIF-1α protein under hypoxic conditions.

Sirtuins and hypoxia-inducible transcription factors (HIF) have well-established roles in regulating cellular responses to metabolic and oxidative stress. Recent reports have linked these two protein families by demonstrating that sirtuins can regulate the activity of HIF-1 and HIF-2. Here we investigated the role of SIRT1, a NAD+-dependent deacetylase, in the regulation of HIF-1 activity in hypoxic conditions. Our results show that in hepatocellular carcinoma (HCC) cell lines, hypoxia did not alter SIRT1 mRNA or protein expression, whereas it predictably led to the accumulation of HIF-1α and the up-regulation of its target genes. In hypoxic models in vitro and in in vivo models of systemic hypoxia and xenograft tumor growth, knockdown of SIRT1 protein with shRNA or inhibition of its activity with small molecule inhibitors impaired the accumulation of HIF-1α protein and the transcriptional increase of its target genes. In addition, endogenous SIRT1 and HIF-1α proteins co-immunoprecipitated and loss of SIRT1 activity led to a hyperacetylation of HIF-1α. Taken together, our data suggest that HIF-1α and SIRT1 proteins interact in HCC cells and that HIF-1α is a target of SIRT1 deacetylase activity. Moreover, SIRT1 is necessary for HIF-1α protein accumulation and activation of HIF-1 target genes under hypoxic conditions.

How do we apply video-assisted retroperitoneal necrosectomy with minimal access?

BACKGROUND: The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units. Nevertheless, infected necrosis or persistent multi-organ dysfunction are predictors of poor outcome. In these patients, there is still a need to perform necrosectomy. Open surgery results in extensive operative trauma and is associated with high morbidity and mortality. Therefore, several minimally invasive techniques have been developed recently. Retroperitoneal necrosectomy has been shown to be safe and to reduce morbidity and mortality compared to the open procedure. METHODS AND RESULTS: In an instructive video, we show the technique of video-assisted retroperitoneal necrosectomy with minimal access, including the preoperative percutaneous drainage and several accesses to the necrosis. We discuss the indication for retroperitoneal necrosectomy as well as the optimal time point of the intervention. CONCLUSION: In the management of acute necrotizing pancreatitis, the multidisciplinary approach is crucial. The initial treatment by the intensive care units should be extended to intervention or surgery in case of infected necrosis or persistent multi-organ dysfunction. We show here a minimal access solution with the placement of a percutaneous drain followed by video-assisted retroperitoneal necrosectomy.