Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany.

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 < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). CONCLUSION: Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.

ANTECEDENTES: El impacto del volumen hospitalario en los resultados de la cirugía del cáncer de recto ha sido poco investigado. Este estudio tuvo como objetivo analizar el impacto de los casos anuales de cirugía de cáncer de recto por hospital en la mortalidad postoperatoria (postoperative mortality, POM) y el fracaso en el rescate (failure to rescue, FtR). MÉTODOS: Todos los casos de pacientes hospitalizados con un diagnóstico de cáncer de recto y un código de procedimiento de resección rectal, tratados de 2012 a 2015, se identificaron a partir de datos hospitalarios administrativos a nivel nacional. Los hospitales se agruparon en cinco quintiles según el volumen de casos. Se determinó el número absoluto de pacientes, la POM y el FtR por complicaciones postoperatorias graves. El FtR se definió como la mortalidad hospitalaria después de una complicación postoperatoria documentada. RESULTADOS: Se identificaron 64.349 casos entre 2012 y 2015. La tasa de mortalidad hospitalaria global fue del 3,89% (n = 2.506). Las tasas brutas de mortalidad hospitalaria variaron de 5,34% (n = 687) en hospitales de muy bajo volumen a 2,63% (n = 337) en centros de muy alto volumen, con una tendencia distinta entre las categorías de centros (P < 0,001). En el análisis de regresión logística multivariante utilizando el volumen hospitalario como efecto aleatorio, los hospitales de muy alto volumen (53 intervenciones/año) tenían una razón de oportunidades (odds ratio, OR) ajustada por riesgo de 0,58 (i.c. del 95%: 0,47-0,73) en comparación con la tasa basal de mortalidad hospitalaria en hospitales de muy bajo volumen (6 intervenciones/año) (P < 0,001). La tasa global de complicaciones postoperatorias fue comparable entre los diferentes quintiles de volumen, pero el FtR disminuyó significativamente con el aumento del volumen de casos (15,63% FtR tras una embolia pulmonar en el quintil más alto versus 38,4% en el hospital del quintil más bajo, P = 0,01). CONCLUSIÓN: Los pacientes sometidos a cirugía de cáncer de recto en hospitales de gran volumen presentaron mejores resultados y una disminución de las tasas de fracaso en el rescate por complicaciones graves en comparación con los pacientes tratados en hospitales de bajo volumen.

Nationwide in-hospital mortality following colonic cancer resection according to hospital volume in Germany.

Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identified from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5·8 per cent, ranging from 6·9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4·8 per cent (1239 of 25 825) in very high-volume centres (P < 0·001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0·75 (95 per cent c.i. 0·66 to 0·84) in very high-volume hospitals performing a mean of 85·0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12·7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals.

Effects of anastomotic technique on early postoperative outcome in open right-sided hemicolectomy.

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.

[Incidental finding of mucinous neoplasia of the appendix : Treatment strategies]. / Zufallsbefund muzinöse Neoplasie der Appendix : Therapeutische Strategien.

Tumors of the appendix are not a uniform group but differ significantly in terms of their origin/histology and metastatic behavior. Furthermore, tumors of the appendix are often diagnosed as incidental findings after appendectomy for acute appendicitis. A subgroup of these neoplasms are low-grade appendiceal mucinous neoplasms (LAMN). These are mucus-forming tumors of the appendiceal lumen, which can lead to rupture of the appendix and seeding into the abdominal cavity. Therefore LAMN are considered precursors of pseudomyxoma peritonei (PMP). It is essential to clearly differentiate the subgroups of LAMN as well as the resection status. According to this it is determined whether (radical) appendectomy is a sufficient therapy or further treatment, such as ileocecal resection with hyperthermic intraperitoneal chemotherapy (HIPEC) or cytoreductive surgery (CRS) is necessary. There is no standardized concept regarding the follow-up after resection of LAMN. Generally, it is recommended to perform a computed tomography (CT) scan of the abdomen and determination of tumor markers 6 months postoperatively and then once a year. A recommendation regarding the duration of follow-up is difficult as there are case reports in which PMP has occurred more than 15 years after removal of LAMN.

[Perioperative handling of anticoagulation]. / Perioperativer Umgang mit Antikoagulation.

A growing number of patients in Germany receive a long-term prophylactic anticoagulation with phenprocoumone or one of the novel direct oral anticoagulants (NOAC), such as dabigatran, rivaroxaban or apixaban. The most common indication for an oral anticoagulant therapy is atrial fibrillation (approximately 75%) where the anticoagulant therapy can reduce the risk for an embolic event, particularly stroke by 60%. Operations carried out during such a therapy can result in major bleeding complications. On the other hand, suspending anticoagulant therapy can lead to an increased risk of thromboembolisms. Thus, the preoperative assessment should address the bleeding risk of the planned operation, the individual risk of thromboembolism, as well as other factors, such as patient age and renal function. If the individual assessment shows a substantial risk of perioperative bleeding when anticoagulant treatment is continued and a substantial risk of thromboembolism if the treatment is suspended, then a perioperative bridging, for example with low molecular weight heparin, is necessary. Perioperative bridging also leads to an increased risk of perioperative bleeding. Thus, undifferentiated bridging for all patients with atrial fibrillation with anticoagulant treatment is not recommended. Instead, the indications for a perioperative bridging should be decided according to individual risk profiles.

[Perioperative handling of immunosuppressive therapy]. / Perioperativer Umgang mit immunsuppressiver Therapie.

Every year 16 million operations are performed in Germany. Many patients have an autoimmune disorder, for example rheumatoid arthritis, psoriasis or chronic inflammatory bowel disease, which requires treatment. Immunosuppressants are widely applied. Physicians must make a risk-adapted decision whether the immunosuppressant medication can be continued perioperatively or if certain drugs must be paused and if so, with what risks. The handling of immunosuppressants during the perioperative period is very relevant as many patients, for example with rheumatoid arthritis are in need of a hip or knee replacement or patients with inflammatory bowel disease need an operation due to the chronic illness. The interruption of an immunosuppressant therapy should be discussed in an interdisciplinary board according to the underlying disease, because the continuation of immunosuppressants perioperatively can lead to an increased rate of complications, especially wound healing disorders. If a patient is on a glucocorticoid therapy the following must be considered: during the perioperative period the body has an increased demand for glucocorticoids due to the stress reaction. If glucocorticoids are administered in a dosage of more than 7.5 mg/day equivalent of prednisolone this stress reaction is inhibited. Thus, in these cases a perioperative substitution with hydrocortisone is recommended.

[Perioperative handling of antidiabetic drugs]. / Perioperativer Umgang mit Antidiabetika.

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.

[The use of tumor therapeutics in the perioperative period]. / Perioperativer Umgang mit antitumoralen Medikamenten.

In 2010 Germany had 447,300 new cases of cancer. From 2000 to 2010 the incidence of cancer increased by 21% in men and by 14% in women. The change in the age structure with an aging population is the crucial influencing factor. Various cancer types can now be treated by oral antitumor agents used as a chronic medication. Physicians must decide whether the oral antitumor agents can be continued perioperatively or if certain drugs must be paused and if so, with what risks. Oral antitumor agents are a very heterogeneous group of medication. The use of oral antitumor agents during the perioperative period has not been thoroughly examined, but most often a perioperative interruption is recommended. In general, poor wound healing is a frequent complication of this group of medication. The handling of oral antitumor agents in the perioperative period should be based on an individual decision with consideration of the desired therapy goal as well as the individual prognosis. In general, all oral antitumor agents are chronic medication and are continued until a loss of efficacy or intolerable side effects occur. A potentially curative therapy should be paused for the shortest possible time in order not to jeopardize the remission already achieved. Furthermore, generally accepted recommendations concerning the interval between chemotherapy and a planned operation have not yet been established. A rough rule of thumb could be to plan the operation after the regeneration of the blood count or at the same point in time of the next planned chemotherapy.

[The use of platelet aggregation inhibitors in the perioperative period]. / Perioperativer Umgang mit Thrombozytenaggregationshemmern.

Every year 16 million operations are performed in Germany. Many patients take platelet aggregation inhibitors as a primary or secondary prevention to reduce the risk of cardiovascular events. Especially during the perioperative period, this risk reduction is relevant due to an increased risk for cardiac events (in approximately 6.2% of operations). As a result of a presumed increased risk of bleeding, platelet aggregation inhibitors are often paused perioperatively. Thus, doctors must decide on a risk-adapted basis whether the medication can be continued perioperatively and, if so, with what risks. If acetylsalicylic acid (ASA) treatment is solely used as primary prevention it can be paused during the perioperative period, whereas ASA treatment for secondary prevention should only be paused for operations within narrow confines. When pausing ASA, a sufficient time interval should be maintained before the operation. Furthermore, the ASA withdrawal syndrome with an increased predisposition for clotting is an important phenomenon to be considered. Additionally, the perioperative handling of dual platelet aggregation inhibition needed after coronary stent implantation should be addressed. Due to an increased risk for in-stent thrombosis, dual platelet aggregation inhibition is only reluctantly paused. Emergency surgery must, if not otherwise possible, be carried out even if the dual platelet aggregation inhibition is not paused; however, if the risk for intraoperative bleeding is too high and the risk of an in-stent thrombosis is lower in comparison, P2Y12 inhibitors (e.g. clopidogrel) should be paused and the operation carried out solely with ASA therapy.

The bcl, NFkappaB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-beta or TNF-alpha on activated hepatic stellate cells.

Activated hepatic stellate cells (HSC) are thought to play a pivotal role in development of liver fibrosis which takes place in chronic liver diseases. Previous studies have shown that "activated" rat HSC undergo spontaneous apoptosis probably through the CD95/CD95L pathway. TGF-beta as well as TNF-alpha reduced spontaneous apoptosis and CD95L expression. The aim of this study was to investigate the possible mechanisms responsible for the spontaneous apoptosis and for the anti-apoptotic effect of TGF-beta and TNF-alpha on activated HSC. While bcl-2, bax, NFkappaB and p53 gene expression were spontaneously upregulated, bcl-xL and p21WAF1 gene expression decreased and IkappaB remained unchanged during the activation process in vitro. TGF-beta as well as TNF-alpha induced activation of NFKB and upregulated bcl-xL. The latter was inhibited by overexpression of IkappaB. By suppressing spontaneous apoptosis TGF-beta as well as TNF-alpha inhibited p53 gene expression while that of the p21WAF1 gene was increased. We conclude that TGF-beta as well as TNF-alpha may act as surviving factors for activated rat HSC not only through reduction of CD95L gene expression but also by upregulating the anti-apoptotic factors NFKB, bcl-xL and p21WAF1 and by downregulating the proapoptotic factor p53. The interaction with these factors may lead to the generation of new antifibrotic drugs.

Errors: can indicators measure the magnitude?

Errors in medicine, especially medication errors, have long been recognized as a dimension of quality of care and organizational performance. Recently, however, the magnitude of the issue, or its potential impact on cost, quality of care and patient safety have catapulted this issue to the forefront of national debate on the appropriateness of patient care management. There are still fundamental issues associated with the measurement of errors. Should errors that do not cause patient harm receive much attention? Could there be organizational or system issues that predispose to errors? Are there acceptable measurement models that allow comparative analysis and trending of institutional error rate profiles? This paper presents a systematic review of the measurement aspects for errors in medicine, emphasizing the medication errors' dimension. An indicator-based, epidemiological model of measurement is proposed which will allow a systematic inquiry into the issues of both preventable and non-preventable errors and their potential for patient harm.

Developing performance measures for sedation and analgesia: the approach of the Quality Indicator Project.

This article describes the development of a set of measures focused on use of and complications following sedation and analgesia. This group of measures is another step in a 15-year quest of a group of hospitals and other healthcare providers to identify ways to better monitor and understand performance--and thereby improve their ability to identify opportunities for improvement. The article describes in detail the practical steps taken to develop, test, and implement the measures, as well as some of the fundamental conceptual issues associated with cost and benefits of performance measurement. Finally, it examines the pilot-test experience for the measures--both the individual hospitals' efforts to implement data collection and the aggregate data that resulted from the pilot test.

The health of merchant seamen in Baltimore and its history.

This article provides the history of health care provisions for seamen in Baltimore and presents an analysis of the distribution of diseases of merchant seamen in baltimore in 1995.

Transforming growth factor beta and tumor necrosis factor alpha inhibit both apoptosis and proliferation of activated rat hepatic stellate cells.

Transforming growth factor beta (TGF-beta) as well as tumor necrosis factor alpha (TNF-alpha) gene expression are up-regulated in chronically inflamed liver. These cytokines were investigated for their influence on apoptosis and proliferation of activated hepatic stellate cells (HSCs). Spontaneous apoptosis in activated HSC was significantly down-regulated by 53% +/- 8% (P <.01) under the influence of TGF-beta and by 28% +/- 2% (P <.05) under the influence of TNF-alpha. TGF-beta and TNF-alpha significantly reduced expression of CD95L in activated HSCs, whereas CD95 expression remained unchanged. Furthermore, HSC apoptosis induced by CD95-agonistic antibodies was reduced from 96% +/- 2% to 51 +/- 7% (P <.01) by TGF-beta, and from 96% +/- 2% to 58 +/- 2% (P <.01) by TNF-alpha, suggesting that intracellular antiapoptotic mechanisms may also be activated by both cytokines. During activation, HSC cultures showed a reduced portion of cells in the G0/G1 phase and a strong increment of G2-phase cells. This increment was significantly inhibited (G1 arrest) by administration of TGF-beta and/or TNF-alpha to activated cells. In liver sections of chronically damaged rat liver (CCl4 model), using desmin and CD95L as markers for activated HSC, most of these cells did not show apoptotic signs (TUNEL-negative). Taken together, these findings indicate that TGF-beta and/or TNF-alpha both inhibit proliferation and also apoptosis in activated HSC in vitro. Both processes seem to be linked to each other, and their inhibition could represent the mechanism responsible for prolonged survival of activated HSC in chronic liver damage in vivo.

CD95/CD95L-mediated apoptosis of the hepatic stellate cell. A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair.

During liver tissue repair, hepatic stellate cells (HSC), a pericyte-like mesenchymal liver cell population, transform from a "quiescent" status ("resting" HSC) into myofibroblast-like cells ("activated" HSC) with the latter representing the principle matrix synthesizing cell of the liver. Presently, the mechanisms that terminate HSC cell proliferation when tissue repair is concluded are poorly understood. Controlled cell death known as apoptosis could be a mechanism underlying this phenomenon. Therefore, apoptosis and its regulation were studied in HSC using an in vitro and in vivo approach. Spontaneous apoptosis became detectable in parallel with HSC activation because resting cells (2 days after isolation) displayed no sign of apoptosis, whereas apoptosis was present in 8% (+/- 5%) of "transitional" cells (day 4) and in 18% (+/- 8%) of fully activated cells (day 7). Both CD95 (APO-1/Fas) and CD95L (APO-1-/Fas-ligand) became increasingly expressed during the course of activation. Apoptosis could be fully blocked by CD95-blocking antibodies in normal cells and HSC already entering the apoptotic cycle. Using CD95-activating antibodies, transition of more than 95% cells into apoptosis was evident at each activation step. The apoptosis-regulating proteins Bcl-2 and p53 could not be detected in resting cells but were found in increasing amounts at days 4 and 7 of cultivation. Whereas p53 expression was induced by the CD95-activating antibody, no change was inducible in Bcl-2 expression. The Bcl-2-related protein bax could be found at days 2 and 4 in similar expression, was considerably up-regulated at day 7, but was not regulated by CD95-agonistic antibodies. In vivo, acute tissue damage was first accompanied by activation and proliferation of HSC displaying no sign of apoptosis. In the recovery phase, apoptotic HSC were detectable in parallel to a reduction in the total number of HSC present in the liver tissue. The data demonstrate that apoptosis becomes detectable in parallel with HSC activation, which suggests that apoptosis might represent an important mechanism terminating proliferation of activated HSC.