Validation of the Surgical Outcome Risk Tool (SORT) and SORT v2 for Predicting Postoperative Mortality in Patients with Pancreatic Cancer Undergoing Surgery

BACKGROUND: Pancreatic cancer surgery is related to significant mortality, thus necessitating the accurate assessment of perioperative risk to enhance treatment decision making. A Surgical Outcome Risk Tool (SORT) and SORT v2 have been developed to provide enhanced risk stratification. Our aim was to validate the accuracy of SORT and SORT v2 in pancreatic cancer surgery. METHOD: Two hundred and twelve patients were included and underwent pancreatic surgery for cancer. The surgeries were performed by a single surgical team in a single tertiary hospital (2016-2022). We assessed a total of four risk models: SORT, SORT v2, POSSUM (Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity), and P-POSSUM (Portsmouth-POSSUM). The accuracy of the model was evaluated using an observed-to-expected (O:E) ratio and the area under the curve (AUC). RESULTS: The 30-day mortality rate was 3.3% (7 patients). Both SORT and SORT v2 demonstrated excellent discrimination traits (AUC: 0.98 and AUC: 0.98, respectively) and provided the best-performing calibration in the total analysis. However, both tools underestimated the 30-day mortality. Furthermore, both reported a high level of calibration and discrimination in the subgroup of patients undergoing pancreaticoduodenectomy, with previous ERCP, and CA19-9 ≥ 500 U/mL. CONCLUSIONS: SORT and SORT v2 are efficient risk-assessment tools that should be adopted in the perioperative pathway, shared decision-making (SDM) process, and counseling of patients with pancreatic cancer undergoing surgery

Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 +/- A 11 vs 64 +/- A 18 %; p = 0.03) and overall survival (58 +/- A 12 vs 83 +/- A 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.Canadian Institutes of Health Research [MOP 82727]info:eu-repo/semantics/publishedVersio

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

The use of sirtex in inoperable liver tumours. A surgeon's view

Over the past few years, selective internal radiation therapy (SIRT) has been used clinically for the treatment of non-resectable hepatic metastases in the absence of extrahepatic metastases and in combination with hepatic arterial chemotherapy. The procedure involves using Yttrium-90 microspheres (25-35 u in diameter (fig. 32b. 1), that are injected using a syringe into the hepatic artery via an access route: either a trans-femoral catheter or a permanently implanted hepatic artery port with catheter (fig. 32b.2). Once injected, the spheres travel through the blood stream and target the tumour within the liver, delivering high doses of beta radiation of 0.93 MeV energy, with a maximum 11 mm and mean 2.5 mm penetration distance [1, 2]. Treatment takes around 20-30 minutes and is delivered under mild sedation. In a randomised controlled trial of selective internal radiation therapy in combination with chemotherapy, patients receiving SIRT had improved response rates as measured by tumour area, volume and CEA in comparison to those patients receiving chemotherapy alone. However, evidence on survival indicated no statistically significant difference in the outcomes of patients receiving SIRT, compared with those treated with chemotherapy alone. More or less, this treatment modality has been increasingly adopted in recent years with a great enthusiasm for management of patients with liver cancer as an established treatment option without a clear evidence of survival benefit and its cost implications [3]. © 2006 Springer-Verlag/ Wien

Implementation of Routine Computed Tomography (CT) Following Laparoscopic Sleeve Gastrectomy: New Evidence Brings New Challenges

[No abstract available

Basics of radiofrequency tissue ablation

Surgical advances generally follow either a scientific discovery or a technological breakthrough, for example magnetic resonance imaging or joint replacement. Over the past few years, the advent of new energy sources, such as radiofrequency, has had an increasing impact on surgical practice, especially in the field of liver tumours. Liver resection presently offers the only opportunity for cure in patients with liver cancer, either primary or secondary. Unfortunately, most hepatic cancers are unsuitable for curative resection at the time of diagnosis. Limitations for surgical resection can broadly be classified as either: 1) tumour-related, i.e. lesions that are extremely large, awkwardly sited, multiple, involving major vascular structures, associated with extrahepatic disease or 2) patient-related, i.e. intercurrent medical conditions, old age and poor liver function, especially in those with underlying cirrhosis. Therefore, there is a clear need, for the development of a simple and effective technique to control unresectable tumours within the liver and, preferably, one that avoids a lengthy hos pital stay in patients with limited duration of survival. In the past few years, minimal access has beco me available for the destruction of hepatic carcinomas by methods such as ethanol injection and thermoablation, with cryoprobes, laser or radiofrequency. Radiofrequency ablation (RFA) has now been widely accepted as an effective modality for treating liver turnouts that are unsuitable for resection. It is based on the conversion of radiofrequency waves into heat, leading to coagulative necrosis, and it can be delivered either percutaneously or at open operation. © 2006 Springer-Verlag/Wien