Ribociclib in newly diagnosed hepatitis B infection: A case report

Breast cancer is the most frequently diagnosed cancer in women worldwide. Actually CDK4/6 inhibitor Ribociclib is approved for the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer, but comorbidities like infectious or cardiovascular diseases may limit its use.Case reportA 45-year-old woman was diagnosed with metastatic breast cancer in September 2021; also, her hepatitis screening resulted positive for hepatitis B infection. Patient assumed eradicative therapy for hepatitis and bit after started oncological therapy with Ribociclib.OutcomeFrequent check of hepatological function was observed since start of eradicative therapy; liver transaminases and bilirubin kept to not rise despite start of oncological treatment with Ribociclib. Patient’s Performance Status was also not compromised and revaluation at 4, 9 and 13 months showed partial response and then stable disease.Discussionhepatotoxicity of Ribociclib is reported as a possible side effect, and often positivity for hepatitis is cause of exclusion from therapy; in our case, no hepatotoxicity was noted and patient obtained response in terms of control of both infectious and oncological diseases

Identification of Distinctive Patterns of USP19-Mediated Growth Regulation in Normal and Malignant Cells

We previously reported that the USP19 deubiquitinating enzyme positively regulates proliferation in fibroblasts by stabilizing KPC1, a ubiquitin ligase for p27Kip1. To explore whether this role of USP19 extends to other cellular systems, we tested the effects of silencing of USP19 in several human prostate and breast models, including carcinoma cell lines. Depletion of USP19 inhibited proliferation in prostate cancer DU145, PC-3 and 22RV1 cells, which was similar to the pattern established in fibroblasts in that it was due to decreased progression from G1 to S phase and associated with a stabilization of the cyclin-dependent kinase inhibitor p27Kip1. However, in contrast to previous findings in fibroblasts, the stabilization of p27Kip1 upon USP19 depletion was not associated with changes in the levels of the KPC1 ligase. USP19 could also regulate the growth of immortalized MCF10A breast epithelial cells through a similar mechanism. This regulatory pattern was lost, though, in breast cancer MCF7 and MDA-MB-231 cells and in prostate carcinoma LNCaP cells. Of interest, the transformation of fibroblasts through overexpression of an oncogenic form of Ras disrupted the USP19-mediated regulation of cell growth and of levels of p27Kip1 and KPC1. Thus, the cell context appears determinant for the ability of USP19 to regulate cell proliferation and p27Kip1 levels. This may occur through both KPC1 dependent and independent mechanisms. Moreover, a complete loss of USP19 function on cell growth may arise as a result of oncogenic transformation of cells

Bowel preparation for elective colorectal resection: multi-treatment machine learning analysis on 6241 cases from a prospective Italian cohort

background current evidence concerning bowel preparation before elective colorectal surgery is still controversial. this study aimed to compare the incidence of anastomotic leakage (AL), surgical site infections (SSIs), and overall morbidity (any adverse event, OM) after elective colorectal surgery using four different types of bowel preparation. methods a prospective database gathered among 78 Italian surgical centers in two prospective studies, including 6241 patients who underwent elective colorectal resection with anastomosis for malignant or benign disease, was re-analyzed through a multi-treatment machine-learning model considering no bowel preparation (NBP; No. = 3742; 60.0%) as the reference treatment arm, compared to oral antibiotics alone (oA; No. = 406; 6.5%), mechanical bowel preparation alone (MBP; No. = 1486; 23.8%), or in combination with oAB (MoABP; No. = 607; 9.7%). twenty covariates related to biometric data, surgical procedures, perioperative management, and hospital/center data potentially affecting outcomes were included and balanced into the model. the primary endpoints were AL, SSIs, and OM. all the results were reported as odds ratio (OR) with 95% confidence intervals (95% CI). results compared to NBP, MBP showed significantly higher AL risk (OR 1.82; 95% CI 1.23-2.71; p = .003) and OM risk (OR 1.38; 95% CI 1.10-1.72; p = .005), no significant differences for all the endpoints were recorded in the oA group, whereas MoABP showed a significantly reduced SSI risk (OR 0.45; 95% CI 0.25-0.79; p = .008). conclusions MoABP significantly reduced the SSI risk after elective colorectal surgery, therefore representing a valid alternative to NBP

Abdominal drainage after elective colorectal surgery: propensity score-matched retrospective analysis of an Italian cohort

background: In italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. the aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery. methods: a database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. the primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. the results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i. results: a total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). group a versus group B showed a significantly lower risk of postoperative duration of stay >6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P < 0.001). a mean postoperative duration of stay difference of 0.86 days was detected between groups. no difference was recorded between the two groups for all the other endpoints. conclusion: this study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery

Three-row versus two-row circular staplers for left-sided colorectal anastomosis: a propensity score-matched analysis of the iCral 2 and 3 prospective cohorts

Background: Since most anastomoses after left-sided colorectal resections are performed with a circular stapler, any technological change in stapling devices may influence the incidence of anastomotic adverse events. The aim of the present study was to analyze the effect of a three-row circular stapler on anastomotic leakage and related morbidity after left-sided colorectal resections. Materials and methods: A circular stapled anastomosis was performed in 4255 (50.9%) out of 8359 patients enrolled in two prospective multicenter studies in Italy, and, after exclusion criteria to reduce heterogeneity, 2799 (65.8%) cases were retrospectively analyzed through a 1:1 propensity score-matching model including 20 covariates relative to patient characteristics, to surgery and to perioperative management. Two well-balanced groups of 425 patients each were obtained: group (A) – true population of interest, anastomosis performed with a three-row circular stapler; group (B) – control population, anastomosis performed with a two-row circular stapler. The target of inferences was the average treatment effect in the treated (ATT). The primary endpoints were overall and major anastomotic leakage and overall anastomotic bleeding; the secondary endpoints were overall and major morbidity and mortality rates. The results of multiple logistic regression analyses for the outcomes, including the 20 covariates selected for matching, were presented as odds ratios (OR) and 95% confidence intervals (95% CI). Results: Group A versus group B showed a significantly lower risk of overall anastomotic leakage (2.1 vs. 6.1%; OR 0.33; 95% CI 0.15–0.73; P = 0.006), major anastomotic leakage (2.1 vs. 5.2%; OR 0.39; 95% CI 0.17–0.87; P = 0.022), and major morbidity (3.5 vs. 6.6% events; OR 0.47; 95% CI 0.24–0.91; P = 0.026). Conclusion: The use of three-row circular staplers independently reduced the risk of anastomotic leakage and related morbidity after left-sided colorectal resection. Twenty-five patients were required to avoid one leakage

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

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

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

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

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised