Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established.
We conducted a ...multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity.
Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37%
27%) and compliance with CRT higher in group B (91%, 78%, and 76%
97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90
45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B (
< .001), but not group A (
= .210), fulfilled the predefined statistical hypothesis.
Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.
A randomized trial compared peroral endoscopic myotomy with laparoscopic Heller’s myotomy plus Dor’s fundoplication in patients with symptomatic idiopathic achalasia. POEM was noninferior to LHM in ...controlling symptoms of achalasia at 2 years. Symptoms of gastroesophageal reflux were more common in the POEM group.
The German Cancer Society (“Deutsche Krebsgesellschaft”; DKG) certifies on a volunteer base colorectal cancer centers based on, among other things, minimum operative amounts (at least 30 oncological ...colon cancer resections and 20 oncological rectal cancer resections per year). In this work, nationwide hospital mortality and death after documented complications (‘Failure to Rescue’ = FtR) were evaluated depending on the fulfillment of the minimum amounts.
This is a retrospective analysis of the nationwide hospital billing data (DRG data, 2012–2017). Categorization is based on the DKG minimum quantities (fully, partially or not fulfilled).
Of 287,227 patients analyzed, 56.5% were operated in centers that met the DKG minimum amounts. The overall hospital mortality rate was 5.0%. In centers which met the minimum quantities, it was significantly lower (4.3%) than in hospitals which partially (5.7%) or not (6.2%) met the minimum quantities. The risk-adjusted hospital mortality rate for patients in hospitals who meet the minimum amount was 20% lower (OR 0.80; 95% CI 0.74–0.87, p < 0.001). For complications, both surgical and non-surgical, there was an unadjusted and adjusted lower FtR in hospitals that met the minimum amounts (e.g. anastomotic leak: 11.2% vs. 15.6%, p < 0.001; pulmonary artery embolism 21.3% vs. 28.2%, p = 0.001).
There is a 1/3 lower mortality and FtR rate after surgery for a colon or rectal cancer in centers fulfilling the DKG minimum amounts. The presented data implicate that there is an urgent need for a nationwide centralization program.
Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are ...frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys‐558‐Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.
Summary
Background
After partial resection of the thyroid gland, a second operation referred to as “completion thyroidectomy” may be required if histopathological analysis indicates the presence of ...differentiated thyroid cancer (DTC). Although there is little evidence, it is assumed that the time point of completion thyroidectomy is not critical for oncological prognosis of patients with DTC. We assessed whether patients with total thyroidectomy (TTx) in a two‐step procedure have an equal long‐term prognosis with regard to disease‐specific survival (DSS) compared to patients immediately undergoing total thyroidectomy in a one‐step procedure.
Methods
A database study using the Würzburg thyroid cancer database with 2258 patients with pT1a‐pT4b tumours DTC who were operated between 1980 and 2016 was carried out.
Results
A total of 277 patients with papillary microcarcinoma pT1aN0M0 were treated by hemithyroidectomy. TTx as one‐step procedure was performed in 1114 patients compared to 867 with TTx as a two‐step procedure. Patients with papillary thyroid cancer more frequently had a TTx as one‐step procedure than follicular thyroid cancer patients (59.4% vs 47%; P < 0.001). Compared to a one‐step thyroidectomy, overall complication rate was not different compared to patients undergoing a single operation. Multivariate analysis showed that the presence of distant metastases, T‐stage and age at diagnosis were the only independent determinants for DTC‐specific survival, regardless of a one‐ or two‐time thyroidectomy.
Conclusion
The present study on the largest of such patient collectives provides evidence that a delayed completion operation does not affect DSS in DTC, nor does it lead to a significant increase in complication rates.
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.
During the COVID-19 pandemic in 2020 a decrease of emergency consultations and modification in treatment of numerous medical conditions were observed. Aim of this paper was to evaluate the effect of ...the COVID-19 pandemic on incidence, treatment strategies, severity, length of hospital stay and time of presentation in adults and children with acute appendicitis.
A systematic literature search of Pubmed, Embase and Cochrane databases was performed, and eligible studies used to perform a meta-analysis.
46 suitable studies were identified with an overall reduction of appendicitis cases by 20.9% in adults and an increase of 13.4% in children. The rate of open appendectomies increased without statistical significance in both groups (adults: 8.5% vs. 7.1%, P = 0.32; children: 7.1% vs. 5.3%, P = 0.13), whereas the rate of antibiotic treatment increased significantly (P = 0.007; P = 0.03). Higher rates of complicated appendicitis were observed in adults (adults: OR 2.00, P < 0.0001; children: OR 1.64, P = 0.12). Time to first consultation did not change significantly (adults: 52.3 vs. 38.5 h – P = 0.057; children: 51.5 vs. 32.0 h – P = 0.062) and length of stay was also not lengthened during the pandemic (adults: 2.9 vs. 2.7 days, P = 0.057; children: 4.2 vs. 3.7 days, P = 0.062).
The COVID-19 pandemic of 2020 had major impact on incidence and treatment strategies of acute appendicitis. Results of this meta-analysis might be another hint to support the theory that appendicitis is not a progressive disease and surgeons can safely consider antibiotic therapy for acute uncomplicated appendicitis.
•The overall incidence of acute appendicitis decreased by 20.9% in adults and increased by 13.4% in children.•Instead of appendectomy, antibiotic therapy was administered more frequently during the pandemic.•There was an significant increase of complicated appendicitis including perforation and abscess in adults.•Rate of open surgery, length of stay and time from start of symptoms to presentation in the emergency room did not change.
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.
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