Prehab, ERAS, Rehab: A patient care continuum around colo-rectal surgery: Prehabilitation combined with ERAS and rehabilitation to reduce morbidity and hospital stay.

BACKGROUND: Prehabilitation (Prehab) programs aim to optimize patients psycho-physical condition before surgery, to improve post-operative outcomes. Although functional benefits of Prehab are known, the clinical impact does not yet have concrete evidence. The objective of this study is to evaluate the efficacy of Prehab, associated with Enhanced Recovery After Surgery (ERAS) and surgical rehabilitation (Rehab), in frail colorectal oncological patients in terms of morbidity and hospitalization. PATIENTS AND METHODS: The cohort of patients undergoing Prehab between January 2020 and December 2022 (Prehab group) is compared with the historical cohort of patients operated on in the period 01/2018-12/2019, not undergoing Prehab (no-Prehab group). Prehab scheme: multimodal (physiotherapy, clinical nutrition and psychological support). All patients followed an ERAS path. Only Prehab patients followed a surgical Rehab by a dedicated nurse case-manager. Propensity score matching (PSM) and weighting (PSW) analyses were used for statistical analysis. PRIMARY OBJECTIVES: complications at 30 days and hospital stay. SECONDARY OBJECTIVES: functional outcomes. RESULTS: In 3 years of preliminary enrollment, 36 patients completed the program: 22 in person, 16 in tele-prehab. The Prehab group experienced fewer complications than the no-Prehab group (PSM: 31 % vs 53 % p = 0.02; PSW: 31 % vs 51 % p = 0.02), less severe complications (CCI>20 PSM: 17 % vs 33 % p = 0.074; PSW: 17 % vs 53 % 0.026) and shorter hospital stay (4.5 vs 6 days; p = 0.02). Finally, prehabilitated patients improved their preoperative functional capacity and reduced anxiety levels. CONCLUSION: The strategy of combining Prehab with ERAS and Rehab has positively influenced post-operative clinical outcomes as well as functional parameters in our series.

Real-life efficacy and safety of cemiplimab in advanced cervical cancer from a nominal use program in Italy: The MITO 44 study.

BACKGROUND: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy. METHODS: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data. RESULTS: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%. CONCLUSIONS: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

Safety, Effectiveness and Pitfalls of Carbon Dioxide Routine Use as a Contrast Agent for Endovascular Abdominal Aortic Repair.

BACKGROUND: Despite the evidence of good performance, carbon dioxide (CO2) routine employment as a contrast agent for endovascular procedures is far from being adopted with its use currently limited to patients with renal impairment and known allergy to iodinated contrast medium (ICM). The purpose of our study is to evaluate the safety and effectiveness of CO2 guided endovascular abdominal aortic aneurysm repair (EVAR) in a standard population and to assess the rationale for a future widespread use. METHODS: We retrospectively collected data of every patient who underwent CO2 guided standard EVAR from September 2020 to May 2021 and compared them with the data of every patient who underwent EVAR using ICM from December 2019 to August 2020 in our unit. The selection of the contrast medium was not based on any preoperative factor as the contrast medium was routinely used in every patient in both periods. The primary end point of the study was the technical success rate. Secondary end points were the early and late complication rates, radiation exposure and renal function impairment. RESULTS: 49 patients underwent ICM guided EVAR and 52 patients underwent CO2 guided EVAR in our unit in the time frames specified above. The technical success rate was 100% in both groups with no accidental coverage of any target vessel. Intraoperative endoleaks were observed in 14% of ICM patients and 25% of CO2 patients. The radiation exposure was higher in the CO2 group if compared to the ICM group (311.48 vs. 159.86 median mGy/cm2 - P < 0.001). The incidence of postoperative acute kidney injury was low and similar in the 2 groups. No significant worsening over time of the renal function has been reported in both groups. CONCLUSIONS: EVAR can be safely performed under CO2 guidance without the integration of any quantity of ICM but with an increase in radiation exposure. The nephroprotective role of CO2 guided EVAR in a standard population is unclear and the same role in renal impaired patients should be validated with further studies on selected populations.

Inverse probability of treatment weighting analysis of laparoscopic versus open Sg4b-5 bi-segmentectomy in patients with gallbladder cancer.

Sg4b-5 anatomical bi-segmentectomy with regional lymphadenectomy (Sg4b5) is a surgical option for gallbladder cancer (GBC) treatment. The laparoscopic approach to this challenging operation is still controversial. Aim of this study was to compare short- and long-term outcomes of laparoscopic versus open Sg4b5 in a single institution series of patients. All consecutive patients who underwent Sg4b5 for GBC from January 2000 to September 2021 were retrospectively reviewed. Inverse probability of treatment weighting (IPTW) analysis was performed. 75 patients were analyzed, 18 in the laparoscopic and 57 in the open group. After IPTW, laparoscopic approach was associated with a significantly decreased median intraoperative blood loss (100 vs 237.09 ml, p = 0.001), shorter median length of hospital stay (4 vs 8 days, p = < 0.001) and a higher median number of harvested nodes (9 vs 7, p = 0.026). Operation time was shorter in the open group (355 vs 259 min, p < 0.001). No significant differences were found regarding clear resection margins, overall and major (Clavien-Dindo ≥ 3) morbidity, bile leakage rate, 90 days post-operative mortality, overall and disease-free survival. Laparoscopic Sg4b-5 anatomical bi-segmentectomy and regional lymphadenectomy is feasible and safe with long term outcome comparable to open approach at least in early stages. Laparoscopic approach confirms its well-known short-term benefits with less intraoperative bleeding and shorter length of stay. Moreover, it might allow a better lymphadenectomy.

MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)-Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors-A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study.

OBJECTIVE: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. METHODOLOGY: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group. RESULTS: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10-12) in the control group vs. 8 months (95% IC 6-9) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28-5.06) for the case group (p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand-foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented. CONCLUSION: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.

A close adherence to a stoma-therapeutic pathway improves immediate stoma-related outcomes and reduces the length of hospital stay.

PURPOSE: New stoma creation is related to a wide range of implications and stoma-related complications could occur frequently. The aim was to assess the impact of a close stoma-therapeutic-care pathway (STCP) in terms of length of stay, autonomy in the management of the pouch, readmission rate, and stoma-related complications. METHODS: Patients undergoing surgery for colorectal disease and first stoma creation from January 2017 to December 2020 were analyzed. All patients enrolled had joined the Enhanced Recovery after Surgery (ERAS) protocol. RESULTS: Among 143 enrolled, 56 (40%) did not completely follow the STCP (group A), whereas 87 (60%) demonstrated strict compliance (group B). The hospital stay lasted 8 days in group B and 11.5 in group A (p = 0.001). The first look at the stoma needed 1 day in group B and 3 days in group A (p < 0.001), emptying the pouch 2 days in group B and 5 days in group A (p < 0.001). Finally, the ability to change the pouch was 3 days in group B and 6 days in group A (p < 0.001). Nine (16.1%) stoma-related complications were counted in group A and 16 (18.4%) in group B, and 30-day readmission was 10.1% in group B and 11.5% in group A (p = 0.82 and p = 1, respectively, not significant). CONCLUSIONS: The STCP has been shown to reduce the hospital stay and to have a protective role making the patient autonomous in the management of the stoma.

MRI-detected extramural vascular invasion (mrEMVI) as the best predictive factor to identify candidates to total neoadjuvant therapy in locally advanced rectal cancer.

BACKGROUND AND OBJECTIVES: Chemotherapy in locally advanced rectal cancer (LARC) is shifting from an adjuvant setting to a total neoadjuvant therapy (TNT) strategy, that relies on distant metastases (DM) risk prediction. This study aims to assess the accuracy of magnetic resonance imaging-detected extramural vascular invasion (mrEMVI) as predictive factor for DM in LARC, compared with other MRI-detected and pathologic factors. METHODS: This retrospective single-center study analyzed data extracted from a series of consecutive patients curatively resected for rectal cancer at Mauriziano Hospital in Turin (Italy) from January 2013 to December 2018. RESULTS: Data from 69 patients were analyzed. MrEMVI was detected in 31 (44.9%) cases. Median follow-up was 39.9 months. DM and local recurrence occurred in 19 (27.5%) and 4 (5.8%) patients. One- and 3-year cumulative incidence of DM were 32.3% (95% confidence interval [CI]: 0.17-0.49) and 56.8% (95% CI: 0.35-0.74) in the mrEMVI-positive group and 5.4% (95% CI: 0.01-0.16) and 14.0% (95% CI: 0.05-0.27) in the mrEMVI-negative group (log-rank test, p < 0.001). In the multivariate analysis of MRI factors, mrEMVI was the only independent predictor of DM (HR: 3.59, CI: 1.21-10.69, p = 0.02). CONCLUSIONS: This study confirmed that mrEMVI is a powerful predictor of DM in LARC. It should be routinely reported and considered during multidisciplinary care strategy planning.

Incidence and Prevalence Analysis of Non-Small-Cell and Small-Cell Lung Cancer Using Administrative Data.

Treatment of lung cancer depends on the stage of the tumor and the histological type. In recent years, the histological confirmation of lung non-small-cell lung cancer has become crucial since the availability of selective target therapeutic approaches. The aim of the study was to develop a validated procedure to estimate the incidence and prevalence of non-small-cell and small-cell lung cancer from healthcare administrative data. A latent class model for categorical variables was applied. The following observed variables were included in the analysis: ICD-9-CM codes in the Hospital Discharge Registry, ATC codes of medications dispensed present in the Drugs Prescriptions Registry, and the procedure codes in the Outpatient Registry. The proportion of non-small-cell lung cancer diagnoses was estimated to be 85% of the total number of lung cancer on the cohort of incident cases and 89% on the cohort of prevalent cases. External validation on a cohort of 107 patients with a lung cancer diagnosis and histological confirmation showed a sensitivity of 95.6% (95%CI: 89-98.8%) and specificity of 94.1% (95%CI: 71.3-99.9%). The procedure is an easy-to-use tool to design subpopulation-based studies on lung cancer and to better plan resource allocation, which is important since the introduction of new targeted therapies in non-small-cell lung carcinoma.

Radioembolization vs sorafenib in locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score and Bayesian analysis.

OBJECTIVE: In this study we aimed to compare patient outcomes between the use of transarterial radioembolization (TARE) and sorafenib in patients with hepatocellular carcinoma (HCC) and intrahepatic portal vein tumor thrombosis (PVTT). METHODS: A total of 65 patients with HCC and intrahepatic PVTT treated in five Italian hospitals between 2012 and 2018 were included in the analysis. Those with any previous treatment, extension of PVTT to the main portal tract and extrahepatic involvement were excluded. Propensity score matching analysis and Bayesian model averaging analysis were performed. RESULTS: Of the 41 patients treated with TARE and 24 with sorafenib, 11 patients were downstaged to curative-intent surgery (liver transplant in three and hepatectomy in eight), including 10 treated with TARE and one with sorafenib. TARE was more effective than sorafenib in downstaging patients to surgery, achieving a mean survival of 54 months. In the 54 patients without downstaging after treatment, of whom 31 were treated with TARE and 23 with sorafenib, median survival was 20.3 and 9.1 months, respectively (P = 0.001), with different 1-, 2- and 3-year OS rates (64.5%, 42.6% and 37.3% vs 39.1%, 13.0% and 0%). Both propensity score and Bayesian model averaging confirmed an improvement in overall survival in the TARE group compared with sorafenib treatment. CONCLUSIONS: TARE was more effective than sorafenib in downstaging patients with HCC to surgery, providing a significant improvement in survival. Even in patients who were not downstaged to surgery, survival appeared to be superior with TARE over sorafenib.

Long-term failure after endovascular aneurysm sealing in a real-life, single-center experience with the Nellix endograft.

BACKGROUND: Endovascular aneurysm sealing (EVAS) is an innovative alternative to conventional endovascular aneurysm repair (EVAR). EVAS relies on sac anchoring without proximal fixation to achieve sealing and should have allowed for the treatment of a broader range of anatomic features compared with standard EVAR. Despite the encouraging early reports, the mid- and long-term follow-up data have shown increased rates of failure. To address the issue, the manufacturer introduced revised instructions for use (IFU) in 2016. The present study reports the outcomes of this system after a median follow-up of 45 months. METHODS: Data for all patients electively treated with EVAS at our institution were retrospectively collected. The patients were retrospectively reclassified according to the 2016 revised IFU of the device. All patients in the present series had undergone EVAS for the treatment of infrarenal abdominal aortic aneurysms (AAAs). The primary end point was therapeutic failure: graft migration >5 mm, sac expansion >5 mm, type IA endoleak (Is2 and Is3 using the Van den Ham classification), type Ib endoleak, and secondary rupture. The overall mortality, aortic-related mortality, and reintervention rates were also analyzed. RESULTS: A total of 101 patients had undergone elective treatment by EVAS from 2013 to 2018 for infrarenal AAAs. The median follow-up was 3.75 years. Therapeutic failure was observed in 31 of the 101 patients (30.7%), with no significant difference between the in-IFU and off-IFU 2016 subgroups. Failure occurred at a median interval of 34 months from the index procedure. Of the 101 patients, 6.9% had presented with secondary rupture. Freedom from aneurysm-related mortality was 96.9% at 1 and 2 years and 89.9% at 5 years. Freedom from reintervention decreased over time: 94.7% at 1 year, 77% at 4 years, and 52.1% at 6 years. Of the 101 patients, 14 (13.9%) had undergone emergent or elective graft explantation. CONCLUSIONS: EVAS performed worse than conventional endografts for several critical end points, regardless of any preoperative anatomic parameters. The incidence of therapeutic failures tended to increase over time, especially 4 years after the index procedure.

The role of cosubstrate and mixing on fungal biofilm efficiency in the removal of tannins.

Tannins are polyphenolic compounds produced by plants and they are used in industrial vegetable tanning of leather. Tannins represent one of the low biodegradability substances in tannery wastewaters with high recalcitrant soluble chemical oxygen demand, furthermore high concentration of tannins can inhibit biological treatment. In the present study, four novel rotating submerged packed bed reactors were inoculated with a selected fungal strain to reach a biological degradation of tannins in non-sterile conditions. The selected fungal strain, Aspergillus tubingensis MUT 990, was immobilised in polyurethane foam cubes carriers and inserted inside a submerged rotating cage reactors. The reactors were feed with a solution composed of four tannins: Quebracho (Schinopsis spp.), Wattle (Mimosa spp.), Chestnut (Castanea spp.) and Tara (Caesalpinia spp.). Four reactors with a volume of 4 L each were used, the co-substrate was pure malt extract, the hydraulic retention time was 24 h and the pH setpoint was 5.5. The reactors configuration was chosen to allow the study of the effect of rotation and the co-substrate addition on tannins removal. The experiment lasted two months and it was achieved 80% of chemical oxygen demand and up to 90% dissolved organic carbon removal, furthermore it was detected an important tannase activity.