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Background The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. Methods All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in‐hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. Results Some 64 349 patients were identified. The overall in‐house mortality rate was 3·9 per cent. The crude in‐hospital mortality rate ranged from 5·3 per cent in very low‐volume hospitals to 2·6 per cent in very high‐volume centres, with a distinct trend between volume categories (P, In‐hospital mortality after rectal cancer surgery is strongly correlated with annual hospital caseload. This is the result of an increased failure‐to‐rescue rate in the case of postoperative complications in low‐volume hospitals rather than the result of an increased overall rate of complications. Rectal cancer surgery and hospital volume

Robotic-assisted colon surgery may contain advantages over the laparoscopic approach, but clear evidence is sparse. This study aimed to analyze postoperative inflammation status, short-term outcome and cost-effectiveness of robotic-assisted versus laparoscopic left hemicolectomy. All consecutive patients who received minimal-invasive left hemicolectomy at the Department of Surgery I at the University Hospital of Wuerzburg in 2021 were prospectively included. Importantly, no patient selection for either procedure was carried out. The robotic-assisted versus laparoscopic approaches were compared head to head for postoperative short-term outcomes as well as cost-effectiveness. A total of 61 patients were included, with 26 patients having received a robotic-assisted approach. Baseline characteristics did not differ among the groups. Patients receiving a robotic-assisted approach had a significantly decreased length of hospital stay as well as lower rates of complications in comparison to patients who received laparoscopic surgery (n = 35). In addition, C-reactive protein as a marker of systemic stress response was significantly reduced postoperatively in patients who were operated on in a robotic-assisted manner. Consequently, robotic-assisted surgery could be performed in a cost-effective manner. Thus, robotic-assisted left hemicolectomy represents a safe and cost-effective procedure and might improve patient outcomes in comparison to laparoscopic surgery.

Tumoren der Appendix sind keine einheitliche Gruppe, sondern unterscheiden sich deutlich im Hinblick auf ihren Ursprung/ihre Histologie und ihr Metastasierungsverhalten. Des Weiteren werden diese Tumoren haufig als Zufallsbefund nach Appendektomie im Rahmen einer akuten Appendizitis diagnostiziert. Eine Subgruppe dieser Neoplasien stellen „low-grade muzinose Neoplasien der Appendix“ (LAMN) dar. Hierbei handelt es sich um schleimbildende Tumoren des Appendixlumens, welche im Verlauf zu einer Ruptur der Appendix und Aussaat in der Bauchhohle fuhren konnen. Damit werden LAMN als Vorstufen des Pseudomyxoma peritonei (PMP) angesehen. Essenziell ist die sichere Differenzierung der Subgruppe der LAMN sowie die Erhebung des Resektionsstatus. Hiernach richtet sich, ob mit der (radikalen) Appendektomie bereits eine suffiziente Therapie erreicht wurde oder ob eine operative Erganzung im Sinne einer Ileozokalresektion mit HIPEC oder CRS erfolgen sollte. Hinsichtlich der Nachsorge nach Resektion einer LAMN besteht kein einheitliches Konzept. Generell wird empfohlen, die Nachsorge 6 Monate postoperativ und anschliesend einmal jahrlich mittels einer Abdomen-CT und Bestimmung der Tumormarker durchzufuhren. Eine Empfehlung hinsichtlich der Dauer der Nachsorge erscheint schwierig, da Fallberichte vorliegen, in denen es noch 15 Jahre nach operativer Entfernung einer LAMN zum Auftreten eines PMP gekommen ist.

Access for right hemicolectomy can be gained by median or transverse incision laparotomy. It is not known whether these routes differ with regard to short-term postoperative outcomes.Patients in the DGAV StuDoQ|ColonCancer registry who underwent open oncological right hemicolectomy by median (n = 2389) or transverse laparotomy (n = 1311) were compared regarding Clavien-Dindo classification (CDC) complications (primary endpoint) as well as specific postoperative complications, operation time, length of stay, and MTL30 status (secondary endpoints).A total of 3700 StuDoQ registry patients underwent open oncological right hemicolectomy by median (n = 2389) or transverse laparotomy (n = 1311) without additional interventions. The median and transverse access routes did not differ regarding CDC complication rates (CDC gt; =3a: 13.1% vs. 12.6%; p = 0.90). However, univariate and multivariate analyses showed that operation times (OR 0.71, 95% CI 0.62-0.81; p lt; 0.001), length of stay (OR 0.69, 95% CI 0.6-079; p lt; 0.001), and MTL30 (OR 0.7, 95% CI 0.61-0.81, p lt; 0.001) were significantly reduced in the transverse laparotomy group.For oncological right hemicolectomy, open transverse upper abdominal laparotomy appears to be superior to median laparotomy in short-term course.

Background Despite recent improvements in colonic cancer surgery, the rate of anastomotic leakage after right hemicolectomy is still around 6-7 per cent. This study examined whether anastomotic technique (handsewn or stapled) after open right hemicolectomy for right-sided colonic cancer influences postoperative complications. Methods Patient data from the German Society for General and Visceral Surgery (StuDoQ) registry from 2010 to 2017 were analysed. Univariable and multivariable analyses were performed. The primary endpoint was anastomotic leakage; secondary endpoints were postoperative ileus, complications and length of postoperative hospital stay (LOS). Results A total of 4062 patients who had undergone open right hemicolectomy for colonic cancer were analysed. All patients had an ileocolic anastomosis, 2742 handsewn and 1320 stapled. Baseline characteristics were similar. No significant differences were identified in anastomotic leakage, postoperative ileus, reoperation rate, surgical-site infection, LOS or death. The stapled group had a significantly shorter duration of surgery and fewer Clavien-Dindo grade I-II complications. In multivariable logistic regression analysis, ASA grade and BMI were found to be significantly associated with postoperative complications such as anastomotic leakage, postoperative ileus and reoperation rate. Conclusion Handsewn and stapled ileocolic anastomoses for open right-sided colonic cancer resections are equally safe. Stapler use was associated with reduced duration of surgery and significantly fewer minor complications.

Eine zunehmende Anzahl an Menschen in Deutschland erhalt eine langfristige prophylaktische Antikoagulation mit Phenprocoumon oder einem der neuen direkten oralen Antikoagulanzien (NOAK) wie Dabigatran, Rivaroxaban und Apixaban. Die mit grosem Abstand haufigste Indikation zur oralen Antikoagulation ist Vorhofflimmern (ca. 75 % der Betroffenen), bei welchem das Risiko fur ein embolisches Ereignis, insbesondere Apoplex, durch eine Antikoagulation um ca. 60 % verringert werden kann. Operative Eingriffe, die unter einer solchen Antikoagulation durchgefuhrt werden, konnen schwerwiegende Blutungskomplikationen nach sich ziehen. Dem gegenuber steht das erhohte Thromboembolierisiko im Falle einer Pausierung. Fur den praoperativen Umgang mit der Antikoagulation mussen das eingriffsspezifische Blutungsrisiko, das thromboembolische Risiko sowie weitere Faktoren wie Patientenalter und Nierenfunktion individuell berucksichtigt werden. Zeigt sich nach Prufung des individuellen Risikoprofils einerseits ein nicht akzeptables Blutungsrisiko bei Fortfuhrung der oralen Antikoagulation als auch ein nicht akzeptables Thromboembolierisiko bei perioperativem Absetzen der oralen Antikoagulation, sollte nach heutigem Stand eine perioperative Uberbruckung („bridging“) mit Heparinen erfolgen. Durch Bridging kommt es jedoch zu erhohten Blutungskomplikationen im Vergleich zum Pausieren der Antikoagulation. Ein undifferenziertes Bridging aller Patienten mit Vorhofflimmern oder oraler Antikoagulation wird daher nicht empfohlen, dies sollte anhand des individuellen Risikoprofils entschieden werden.

Pro Jahr werden in Deutschland ca. 16 Mio. operative Eingriffe durchgefuhrt. Eine ganze Reihe von Patienten hat eine Autoimmunerkrankung, z. B. rheumatoide Arthritis, Psoriasis, chronisch-entzundliche Darmerkrankungen, die einer Therapie bedarf. Hier werden vor allem Immunsuppressiva eingesetzt. Im klinischen Alltag ist der operativ tatige Arzt mit der Frage konfrontiert, ob diese perioperativ fortgefuhrt werden konnen oder pausiert werden sollten und wenn ja, mit welchem Risiko. Der perioperative Umgang mit dieser Medikamentengruppe ist auserst relevant, da viele Patienten z. B. mit rheumatoider Arthritis im Verlauf eine totale Knie- oder Huftendoprothese benotigen oder auch Patienten mit chronisch-entzundlichen Darmerkrankungen aufgrund ihrer Erkrankung operiert werden mussen. Das Pausieren einer immunsuppressiven Therapie sollte im interdisziplinaren Konsens anhand der zugrunde liegenden Erkrankung diskutiert werden, da es bei einer Fortfuhrung zu einer erhohten Rate an Komplikationen, vor allem Wundheilungsstorungen, kommen kann. Bekommt ein Patient Glukokortikoide zur Immunsuppression, muss berucksichtigt werden, dass es in der perioperativen Phase zu einer vermehrten Stressreaktion des Korpers kommt, bei der ein erhohter Bedarf an Glukokortikoiden vorhanden ist. Bei einer exogenen Zufuhr (ab 7,5 mg/Tag Prednisolonaquivalent) wird diese Stressantwort inhibiert. Daher wird in diesen Fallen in der perioperativen Phase eine Hydrokortisonsubstitution empfohlen.

Diabetes mellitus is the most frequent metabolic disorder in the western world with a prevalence of 3% in adults under 65 years of age and 14.3% in adults over 65 years of age. Due to the increasing age of our population, the number of patients taking oral antidiabetic drugs has increased. Thus, operating physicians must make a risk-adapted decision whether the medication can be continued perioperatively or if certain drugs must be paused, and if so, with what risks. Operative interventions can lead to a number of metabolic shifts, which change the normal glucose metabolism. Hyperglycemia in the perioperative period is a risk factor for postoperative sepsis, dysfunction of the endothelium, cerebral ischemia and poor wound healing. Due to perioperative fasting oral antidiabetic medication can lead to severe hypoglycemia if taken during this period. This leads to an increased morbidity and mortality in the perioperative period and extends the duration of stay in the intensive care unit (ICU) as well as the overall hospital stay. Oral antidiabetic medication should be paused on the day of the operation and restarted in line with the gradual postoperative return to solid food. Especially metformin, the most commonly used medication in the treatment of type 2 diabetes, should be paused perioperatively due to the severe side effect of lactate acidosis.

Pro Jahr werden in Deutschland ca. 16 Mio. operative Eingriffe durchgefuhrt. Eine nicht unerhebliche Anzahl an Patienten nehmen Thrombozytenaggregationshemmer als Primar- oder Sekundarprophylaxe ein, um das Risiko kardiovaskularer Ereignisse zu reduzieren. Besonders in der perioperativen Phase ist diese Risikoreduktion relevant, da perioperative Myokardinfarkte in bis zu 6,2 % der Operationen festgestellt wurden. Andererseits wird aufgrund des mutmaslich erhohten Blutungsrisikos die Einnahme der Thrombozytenaggregationshemmer perioperativ haufig pausiert. Im klinischen Alltag ist der operativ tatige Arzt mit der Frage konfrontiert, ob diese Medikation perioperativ fortgefuhrt werden kann oder pausiert werden sollte und wenn ja, mit welchem Risiko. Ist die Indikation zur Acetylsalicylsaure(ASS)-Therapie die Primarprophylaxe, so kann die Einnahme perioperativ pausiert werden, wohingegen ASS, welches im Rahmen der Sekundarprophylaxe eingenommen wird, nur bei Operationen in engen Raumen pausiert werden sollte. Wichtig ist es, beim Absetzen auf einen ausreichenden Abstand zur Operation und dem „ASS-withdrawal-Syndrom“ mit erhohter Koagulationsneigung zu achten. Des Weiteren ist der perioperative Umgang mit einer dualen Plattchenaggregationshemmung, die nach Koronarstentimplantation notwendig ist, zu beachten. Aufgrund des erhohten Risikos einer In-Stent-Thrombose wird die duale Plattchenaggregationshemmung ungerne pausiert. Kann eine Operation nicht verschoben werden, so muss im Notfall unter der dualen Plattchenaggregationshemmung operiert werden. Ist jedoch das operative Blutungsrisiko hoch und das Risiko einer In-Stent-Thrombose vergleichsweise gering, so sollte der P2Y12-Inhibitor (z. B. Clopidogrel) pausiert und die Operation unter ASS-Monotherapie durchgefuhrt werden.

Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools, strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2α via the kinases GCN2 and PKR. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, which demonstrates that a negative MYC–eIF2α feedback loop constitutes a targetable vulnerability of colorectal tumours.

Chronic inflammation as an important epigenetic and environmental factor for putative tumorigenesis and tumor progression may be associated with specific activation of Toll-like receptors (TLR). Recently, carcinogenesis has been suggested to be dependent on TLR7 signaling. In the present study, we determined the role of both TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined. For in vitro/in vivo studies TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance. TLR expression was increased in pancreatic cancer, with stage-dependent upregulation in advanced tumors, compared to earlier stages and chronic pancreatitis. Stimulation of TLR7/TLR8 overexpressing PANC1 cells resulted in elevated NF-κB and COX-2 expression, increased cancer cell proliferation and reduced chemosensitivity. More importantly, TLR7/TLR8 expression increased tumor growth in vivo. Our data demonstrate a stage-dependent upregulation of both TLR7 and TLR8 expression in pancreatic cancer. Functional analysis in human pancreatic cancer cells point to a significant role of both TLRs in chronic inflammation-mediated TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance.

Due to its primarily extraperitoneal location, potential affection of the anorectal continence and different metastatic behavior the rectal carcinoma (RC) is classified and treated as an independent disease. Over the past few decades various trials have led to improved multimodal therapies (including radiation, chemotherapy and surgery) for locally advanced rectal cancer and significant changes in the management of this disease whereas the benefit of adjuvant chemotherapy remains unclear. Based on a prospective tumor register of the University Hospital of Wuerzburg data of 263 patients having undergone neoadjuvant therapy and surgical resection for locally advanced rectal cancer were retrieved from the Wuerzburg International database (WID) between October 1992 and September 2013 analyzing the overall survival according to the application of an adjuvant therapy. The cohort consisted of 263 patients with a median age of 65 years (27–89 years), mostly male gender (n = 191; 72.6%) and an ASA performance score of II or III. 143 patients (54.3%) received an adjuvant therapy. Those patients have been significant younger (median 10 years; p

Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n = 9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n = 5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC\(_{50}\)< 3.0 μmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents.

In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress-mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model.Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells.Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo.Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.

Clinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 human CRC cell lines and human endothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. In addition, the efficacy of E7080 against xenografts derived from CRC cell lines and CRC patient resection specimens with mutated KRAS was investigated in vivo. A relatively low cytotoxic effect of E7080 on CRC cell viability was observed in vitro. Endothelial cells (HUVEC) were more susceptible to the incubation with E7080. This is in line with the observation that E7080 demonstrated an anti-angiogenic effect in a three-dimensional ex vivo mouse aortic ring angiogenesis assay. E7080 effectively disrupted CRC cell-mediated VEGF-stimulated growth of HUVEC in vitro. Daily in vivo treatment with E7080 (5 mg/kg) significantly delayed the growth of KRAS mutated CRC xenografts with decreased density of tumor-associated vessel formations and without tumor regression. This observation is in line with results that E7080 did not significantly reduce the number of Ki67-positive cells in CRC xenografts. The results suggest antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS.