Analysis of delay in adjuvant chemotherapy in locally advanced rectal cancer

BackgroundAdjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer.MethodsThe National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4 weeks, intermediate 4-8 weeks, and delayed ≥ 8 weeks. The primary outcome was overall survival.ResultsWe identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01).ConclusionsDelay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy

Effect of Specimen Extraction Site on Postoperative Incisional Hernia after Minimally Invasive Right Colectomy.

BackgroundIncisional hernia (IH) is a known complication after colorectal surgery. Despite advances in minimally invasive surgery, colorectal surgery still requires extraction sites for specimen retrieval, increasing the likelihood of postoperative IH development. The objective of this study is to determine the effect of specimen extraction site on the rate of IH after minimally invasive right-sided colectomy for patients with available imaging.Study designThis is a retrospective multi-institutional cohort study at 2 large academic medical centers in the US. Adults who underwent right-sided minimally invasive colectomy from 2012 to 2020 with abdominal imaging available at least 1 year postoperatively were included in the analysis. The primary exposure was specimen extraction via a midline specimen extraction vs Pfannenstiel specimen extraction. The main outcome was the development of IH at least 1 year postoperatively as visualized on a CT scan.ResultsOf the 341 patients sampled, 194 (57%) had midline specimen extraction and 147 (43%) had a Pfannenstiel specimen extraction. Midline extraction patients were older (66 ± 15 vs 58 ± 16; p < 0.001) and had a higher rate of previous abdominal operation (99, 51% vs 55, 37%, p = 0.01). The rate of IH was higher in midline extraction at 25% (48) compared with Pfannenstiel extraction (0, 0%; p < 0.001). The average length of stay was higher in the midline extraction group at 5.1 ± 2.5 compared with 3.4 ± 3.1 days in the Pfannenstiel extraction group (p < 0.001). Midline extraction was associated with IH development (odds ratio 24.6; 95% CI 1.89 to 319.44; p = 0.004). Extracorporeal anastomosis was associated with a higher IH rate (odds ratio 25.8; 95% CI 2.10 to 325.71; p = 0.002).ConclusionsPatients who undergo Pfannenstiel specimen extraction have a lower risk of IH development compared with those who undergo midline specimen extraction

Two consecutive immunophenotypic switches in a child with MLL-rearranged acute lymphoblastic leukemia.

An 18-month-old girl was diagnosed with prepre-B ALL/t(4;11) leukemia, which during thetreatment and after matched bone marrow transplantation(BMT), underwent two consecutiveswitches from lymphoid to myeloid lineage andvice versa. The high expression of HOXA9 andFLT3 genes remaining genotypically stable in aleukemia throughout phenotypic switches, suggeststhat this leukemia may have originated as acommon B/myeloid progenitors

Robotic-assisted surgery compared with laparoscopic resection surgery for rectal cancer: the ROLARR RCT

This is the final version. Available from NIHR Journals Library via the DOI in this recordData-sharing statement: All available data can be obtained by contacting the corresponding author.Background Robotic rectal cancer surgery is gaining popularity, but there are limited data about its safety and efficacy. Objective To undertake an evaluation of robotic compared with laparoscopic rectal cancer surgery to determine its safety, efficacy and cost-effectiveness. Design This was a multicentre, randomised trial comparing robotic with laparoscopic rectal resection in patients with rectal adenocarcinoma. Setting The study was conducted at 26 sites across 10 countries and involved 40 surgeons. Participants The study involved 471 patients with rectal adenocarcinoma. Recruitment took place from 7 January 2011 to 30 September 2014 with final follow-up on 16 June 2015. Interventions Robotic and laparoscopic rectal cancer resections were performed by high anterior resection, low anterior resection or abdominoperineal resection. There were 237 patients randomised to robotic and 234 to laparoscopic surgery. Follow-up was at 30 days, at 6 months and annually until 3 years after surgery. Main outcome measures The primary outcome was conversion to laparotomy. Secondary end points included intra- and postoperative complications, pathological outcomes, quality of life (QoL) [measured using the Short Form questionnaire-36 items version 2 (SF-36v2) and the Multidimensional Fatigue Inventory-20 (MFI-20)], bladder and sexual dysfunction [measured using the International Prostatic Symptom Score (I-PSS), the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI)], and oncological outcomes. An economic evaluation considered the costs of robotic and laparoscopic surgery, including primary and secondary care costs up to 6 months post operation. Results Among 471 randomised patients [mean age 64.9 years, standard deviation (SD) 11.0 years; 320 (67.9%) men], 466 (98.9%) patients completed the study. Data were analysed on an intention-to-treat basis. The overall rate of conversion to laparotomy was 10.1% and occurred in 19 (8.1%) patients in the robotic-assisted group and in 28 (12.2%) patients in the conventional laparoscopic group {unadjusted risk difference 4.12% [95% confidence interval (CI) –1.35% to 9.59%], adjusted odds ratio 0.61 [95% CI 0.31 to –1.21]; p = 0.16}. Of the nine prespecified secondary end points, including circumferential resection margin positivity, intraoperative complications, postoperative complications, plane of surgery, 30-day mortality and bladder and sexual dysfunction, none showed a statistically significant difference between the groups. No difference between the treatment groups was observed for longer-term outcomes, disease-free and overall survival (OS). Males were at a greater risk of local recurrence than females and had worse OS rates. The costs of robotic and laparoscopic surgery, excluding capital costs, were £11,853 (SD £2940) and £10,874 (SD £2676) respectively. Conclusions There is insufficient evidence to conclude that robotic rectal surgery compared with laparoscopic rectal surgery reduces the risk of conversion to laparotomy. There were no statistically significant differences in resection margin positivity, complication rates or QoL at 6 months between the treatment groups. Robotic rectal cancer surgery was on average £980 more expensive than laparoscopic surgery, even when the acquisition and maintenance costs for the robot were excluded. Future work The lower rate of conversion to laparotomy in males undergoing robotic rectal cancer surgery deserves further investigation. The introduction of new robotic systems into the market may alter the cost-effectiveness of robotic rectal cancer surgery.National Institute for Health Research (NIHR

JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction

The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control

Correction: JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction

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Donor cell acute myeloid leukemia after hematopoietic stem cell transplantation for chronic granulomatous disease: a case report and literature review

The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT. In the subsequent ten years, the AML relapsed three times and the patient underwent chemotherapy and three further HSCTs; donors were the same sister from the first HSCT, an unrelated donor, and his mother. The patient died during the third relapse. The DCL was characterized since onset by an acquired translocation between chromosomes 9 and 11, with a molecular rearrangement between the MLL and MLLT3 genes-a quite frequent cause of AML. In all of the relapses, the malignant clone had XX sex chromosomes and this rearrangement, thus indicating that it was always the original clone derived from the transplanted sister's cells. It exhibited the ability to remain quiescent in the BM during repeated chemotherapy courses, remission periods and HSCT. The leukemic clone then acquired different additional anomalies during the ten years of follow-up, with cytogenetic results characterized both by anomalies frequent in AML and by different, non-recurrent changes. This type of cytogenetic course is uncommon in AML

NUP98-fusion transcripts characterize different biological entities within acute myeloid leukemia: A report from the AIEOP-AML group.

In the last years, collaborative studies have joined to link the degree of genetic heterogeneity of acute myeloid leukemia (AML) to clinical outcome,1, 2 allowing risk stratification before therapy and guiding post-induction treatment of children with AML. So far, still half of these patients, whose disease is usually characterized by a grim prognosis, lack a known biomarker offering opportunities of targeted treatment

CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript

The presence of CBFA2T3‐GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML‐CBFA2T3‐GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3‐GLIS2‐AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3‐GLIS2‐AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA‐DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak‐to‐negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA‐DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance