Angiotensin-converting-Enzym-Hemmer (ACEI) und Angiotensin-Rezeptor-Blocker (ARB) sind häug verwendete Antihypertensiva. Weil Eekte auf aber-rante Gefäßbildung und veränderte Immunantwort beschrieben wurden, wurde geprüft, ob sie mit einem besseren Ansprechen auf die neoadjuvante Strahlentherapie des Rektumkarzinoms assoziiert sind. D azu werteten die Forscher retrospek-tiv zum einen die Daten von 115 Pa-tienten aus, die zwischen 1999 und 2012 an der Universität von Wisconsin wegen eines Rektumkarzinoms mit oder ohne begleitende Chemotherapie neoadjuvant bestrahlt worden waren, um eine kurati-ve Resektion zu ermöglichen. 25 von ih-nen (21,7 %) nahmen zum Zeitpunkt der Strahlentherapie ACEI oder ARB ein. Unabhängig davon wurden die Daten ei-ner Kohorte von 186 Patienten analysiert, die ebenfalls wegen eines Rektumkarzi-noms zwischen 1995 und 2010 an der Universität von Hawaii neoadjuvant be-strahlt worden waren, wobei 49 von ih-nen (26,3 %) ACEI/ARB einnahmen. Den Wisconsin-Daten zufolge war die Einnahme von ACE/ARB mit einer Ver-dreifachung der pathologischen Kom-plettremissionen (pCR) assoziiert (52 vs. 17 %; p = 0,001). In der 2. Kohorte zeigte sich eine signikante Verdoppelung der pCR-Rate bei ACEI/ARB-Einnahme (24 vs. 12 %, p = 0,03). Signikante Unter-schiede bezüglich Patientencharakteris-tika oder Art, Dauer und Intensität der onkologischen erapie bestanden zwi-schen den Gruppen mit und ohne Ein-nahme von Antihypertensiva nicht. Auch zeigten sich keine Assoziationen zwischen pCR-Rate und der Einnahme von anderen Medikamenten. In der mul-tivariaten Analyse aller Daten zusam-men war die Einnahme von ACEI/ARB ein starker Prädiktor für eine pCR (Odds Ratio 4,02; p < 0,001). Damit war die ACEI/ARB-Einnahme sogar ein stärkerer Prädiktor für pCR als klini-sches Stadium oder Grading in der Bi-opsie. Ein Eekt auf das lokalrezidiv-, metastasenfreie oder Gesamtüberleben ließ sich nicht zeigen. Das führen die Forscher auf die zu geringe Zahl der Pa-tienten und die zu kurze Dauer der Be-obachtung (4,1 bzw. 5,3 Jahre) zurück. Fazit: Bei Patienten mit Rektumkarzi-nom war die Einnahme von ACEI/ARB in 2 unabhängigen Kohorten mit einer signikanten Steigerung der pCR-Rate nach der neoadjuvanten erapie asso-ziiert. Morris ZS et al. Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Cancer. 2016;122(16):2487-95. Intensivierung der neoadjuvanten Therapie beim lokal fortgeschrittenen Rektumkarzinom Standard beim lokal fortgeschrittenen Rektumkarzinom ist die totale meso-rektale Exzision mit einer Fluoruracil(FU)-basierten Radiochemotherapie vor und einer adjuvanten Chemotherapie nach der Operation. Ein deutlicher Überlebensvorteil gegenüber einer Operation alleine oder mit adjuvanter Chemotherapie konnte damit aber bisher nicht gezeigt werden. D eshalb wurde in einer Phase-III-Stu-die das Überleben nach modizier-ten multimodalen erapien untersucht. 495 erwachsene chinesische Patienten mit lokal fortgeschrittenem Rektumkar-...

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

BACKGROUNDIn recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.AIMTo establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.METHODSRectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability.RESULTSFour hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypT0-2N0M0 (ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.CONCLUSIONWe established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.