Hepatitis C Virus (HCV) genotypes distribution in South-Eastern Tuscany: a ten-year retrospective study.

Italy is recognized as having the highest Hepatitis C virus (HCV) prevalence in Europe. The Tuscany region, where the prevalence of HCV infection is approximately 0.8%, implemented two programs for the control of chronic hepatitis C in Tuscany from 2018 to 2022. This retrospective study aims to investigate the incidence of HCV in a population screened in Southeastern Tuscany from 2013 to 2022. The study population included 246,137 patients from the provincial area of Arezzo and Grosseto, Tuscany, spanning from January 2013 to October 2022. Among the subjects included in the study, 3,190 (1.29%) tested positive for anti-HCV antibodies. Of this population, 2,119 patients (66.43%) also tested positive for HCV-RNA quantification, leading to their enrolment for subsequent viral genotyping. 1,106 patients had genotype (GT) 1 (52.2%), 484 had GT 3 (22.8%), 371 had GT 2 (17.5%), and 158 had GT 4 (7.5%). Our study underscores the prevalence of HCV GTs 1 and 3 as the most predominant GTs in the Southeast Tuscany region. We also observe a correlation between age, sex and HCV genotypic distribution.

Risk factors for in-hospital mortality after emergency colorectal surgery in octogenarians: results of a cohort study from a referral center.

PURPOSE: The objective of this study was to investigate predictive factors of mortality in emergency colorectal surgery in octogenarian patients. METHODS: It is a retrospective cohort study conducted at a single-institution tertiary referral center. Consecutive patients who underwent emergency colorectal surgery between January 2015 and January 2020 were identified. The primary endpoint was 30-day mortality. Univariate and multivariate analyses were performed using a logistic regression model. RESULTS: A total of 111 patients were identified (43 men, 68 women). Mean age was 85.7 ± 3.7 years (80-96). Main diagnoses included complicated sigmoiditis in 38 patients (34.3%), cancer in 35 patients (31.5%), and ischemic colitis in 31 patients (27.9%). An ASA score of 3 or higher was observed in 88.3% of patients. The mean Charlson score was 5.9. The Possum score was 35.9% for mortality and 79.3% for morbidity. The 30-day mortality rate was 25.2%. Univariate analysis of preoperative risk factors for mortality shows that the history of valvular heart disease (p = 0.008), intensive care unit provenance (p = 0.003), preoperative sepsis (p < 0.001), diagnosis of ischemic colitis (p = 0.012), creatinine (p = 0.006) and lactate levels (p = 0.01) were significantly associated with 30-day mortality, and patients coming from home had a lower 30-day mortality rate (p = 0.018). Intraoperative variables associated with 30-day mortality included ileostomy creation (p = 0.022) and temporary laparostomy (p = 0.004). At multivariate analysis, only lactate (p = 0.032) and creatinine levels (p = 0.027) were found to be independent predictors of 30-day mortality, home provenance was an independent protective factor (p = 0.004). Mean follow-up was 3.4 years. Survival at 1 and 3 years was 57.6 and 47.7%. CONCLUSION: Emergency colorectal surgery is challenging. However, age should not be a contraindication. The 30-day mortality rate (25.2%) is one of the lowest in the literature. Hyperlactatemia (> 2mmol/L) and creatinine levels appear to be independent predictors of mortality.

Evaluation of the SafeHeal Colovac+ anastomosis protection device after low anterior resection for rectal cancer: the safe anastomosis feasibility evaluation (SAFE) 2019 trial.

BACKGROUND: Protective ileostomy (PI) is the current standard of care to protect the anastomosis after low anterior resection (LAR) for rectal cancer, but is associated with significant morbidity. Colovac is an anastomosis protection device designed to shield the anastomosis from fecal content. A second version (Colovac+) was developed to limit the migration risk during the implantation period. The objective of this clinical trial was to evaluate the preliminary efficacy and safety of the Colovac+. METHODS: This was a prospective, multicenter, pilot study aiming to enroll 15 patients undergoing LAR with Colovac+ placement. After 10 days, a CT scan was performed to evaluate the anastomosis and the Colovac+ was retrieved endoscopically. During the 10-day implantation and 3-month follow-up period, we collected data regarding predefined efficacy and safety endpoints. The primary endpoint was the rate of major (Clavien-Dindo III-V) postoperative complications related to the Colovac+ or LAR procedure. RESULTS: A total of 25 patients were included (68% male), of whom 15 were consecutively treated with the Colovac+ and Vacuum Loss Alert System. The Colovac+ was successfully implanted in all 15 patients. No major discomfort was reported during the implantation period. The endoscopic retrieval was performed in 14/15 (93%) patients. The overall major postoperative morbidity rate was 40%, but none of the reported complications were related to the Colovac+. A device migration occurred in 2 (13%) patients, but these were not associated with AL or stoma conversion. Overall, Colovac+ provided effective fecal diversion in all 15 patients and was able to avoid the PI in 11/15 (73%) patients. CONCLUSIONS: Colovac+ provides a safe and effective protection of the anastomosis after LAR, and avoids the PI in the majority (73%) of patients. The improved design reduces the overall migration rate and limits the clinical impact of a migration.

Evaluation of the SafeHeal Colovac+ Anastomosis Protection Device: A Preclinical Study.

BackgroundThe protective ostomy is the current standard of care to protect a low colorectal anastomosis from leakage, but exposes patients to complications requiring an alternative strategy. The Colovac+ is a vacuum-based intraluminal bypass device designed to shield the anastomosis from fecal content, preventing the clinical outcomes of anastomotic leakage. The objective of this study was to evaluate the preliminary efficacy, safety, and technical feasibility of the Colovac+ in a porcine model. Methods: Twelve pigs received a colorectal anastomosis with Colovac+ implantation. The device was left in situ for 10 days and then retrieved endoscopically. Six pigs were to be sacrificed immediately after device retrieval and the other 6 were to be sacrificed on day 38. Clinical, endoscopic, and histopathological examinations were performed to evaluate the following endpoints: prevention of contact between the anastomosis and fecal content, device migration, feasibility of the implantation and retrieval procedure, collateral damage to the colonic wall, colon healing after device retrieval, and systemic toxicity related to the device. Results: Eleven pigs completed the study. One pig died prematurely due to a surgical complication unrelated to the device (bladder damage with uroperitoneum). There was no evidence of contact between the anastomosis and fecal content, none of the pigs developed symptomatic anastomotic leakage, there were no significant device migrations, and there was no evidence of systemic toxicity. Colovac+ implantation was easily performed in all cases except 1 (due to an inappropriate lubricant). Colovac+ retrieval was achieved successfully in all cases. Postretrieval examinations on day 10 revealed ulcerations at the anchoring site in 4 cases indicating mechanical damage caused by the stent. However, in the recovery group, no ulcerations were observed on day 38, and the colonic wall had properly healed in all animals. Conclusions: The Colovac+ is a technically feasible, safe, and efficient device for the protection of a colorectal anastomosis in a porcine model. The device holds promise for clinical use and warrants further research.

In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome.

In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high ß2 -microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time-to-first treatment (P < 0·001) and overall survival (P < 0·001).

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Intraluminal flexible sheath for the protection of low anastomosis after anterior resection: results from a First-In-Human trial on 15 patients.

BACKGROUND: Defunctioning ostomy is commonly used to protect patients from anastomotic leakage complications after low anterior resection, but is fraught with its own deleterious effects. This first-in-human study examines the safety and preliminary efficacy of Colovac, an anastomosis protection device. The Colovac consists of a flexible bypass sheath, placed in the lumen of colon and anchored above the anastomosis using a vacuum stent. METHODS: 15 patients underwent anterior resection (AR) with anastomosis protection by Colovac at 3 European centers. After 14 days, the anastomosis integrity was examined by CT scan and endoscopy. The device was then endoscopically removed. Data regarding demographics, surgical details, 30 day post-operative complications, and patient satisfaction were collected prospectively. RESULTS: 15 patients (10 male) underwent laparoscopic AR with Colovac placement. Preoperative neoadjuvant therapy was administered to 54% of patients. Device placement was uneventful in all patients with a median duration of 7 min and placement was judged as easy or very easy in 93% of the cases. Patients did not report major discomfort during the 14 days. Endoscopic removal (10 min) was judged as easy or very easy in 87% of the cases. Absence of feces below the Colovac anchoring site was observed in 100% of the cases. 4 anastomotic leakages were observed (including 3 device migrations). Overall 5 patients (33%) required a planned stoma creation. At 3 months, 1 had already been closed. CONCLUSION: Colovac provides a minimally invasive protection of the anastomosis during the healing process by avoiding the need for a diverting ostomy for two-thirds of patients who will not experience anastomotic complications and allowing safe conversion to the standard of care for patients requiring extended anastomotic protection. A larger study is ongoing to confirm these results.

In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics.

Complex karyotype (CK) is a negative prognostic factor in chronic lymphocytic leukaemia (CLL). However, CK is a heterogeneous cytogenetic category. Unbalanced rearrangements were present in 73·3% of 90 CLL patients with CK (i.e. ≥3 chromosome aberrations in the same clone), and were associated with a shorter overall survival (P = 0·025) and a shorter time to first treatment (P = 0·043) by multivariate analysis. Patients with unbalanced rearrangements presented a distinct mRNA expression profile. In conclusion, CLL patients with unbalanced rearrangements might represent a subset of very high-risk CLL patients with distinct clinical and biological characteristics.

Prospective Evaluation of Precision Multimodal Gallbladder Surgery Navigation: Virtual Reality, Near-infrared Fluorescence, and X-ray-based Intraoperative Cholangiography.

OBJECTIVE: We aimed to prospectively evaluate NIR-C, VR-AR, and x-ray intraoperative cholangiography (IOC) during robotic cholecystectomy. BACKGROUND: Near-infrared cholangiography (NIR-C) provides real-time, radiation-free biliary anatomy enhancement. Three-dimensional virtual reality (VR) biliary anatomy models can be obtained via software manipulation of magnetic resonance cholangiopancreatography, enabling preoperative VR exploration, and intraoperative augmented reality (AR) navigation. METHODS: Fifty-eight patients were scheduled for cholecystectomy for gallbladder lithiasis. VR surgical planning was performed on virtual models. At anesthesia induction, indocyanine green was injected intravenously. AR navigation was obtained by overlaying the virtual model onto real-time images. Before and after Calot triangle dissection, NIR-C was obtained by turning the camera to NIR mode. Finally, an IOC was performed. The 3 modality performances were evaluated and image quality was assessed with a Likert-scale questionnaire. RESULTS: The three-dimensional VR planning enabled the identification of 12 anatomical variants in 8 patients, of which only 7 were correctly reported by the radiologists (P = 0.037). A dangerous variant identified at VR induced a "fundus first" approach. The cystic-common bile duct junction was visualized before Calot triangle dissection at VR in 100% of cases, at NIR-C in 98.15%, and in 96.15% at IOC.Mean time to obtain relevant images was shorter with NIR-C versus AR (P = 0.008) and versus IOC (P = 0.00000003). Image quality scores were lower with NIR-C versus AR (P = 0.018) and versus IOC (P < 0.0001). CONCLUSIONS: This high-tech protocol illustrates the multimodal imaging of biliary anatomy towards precision cholecystectomy. Those visualization techniques could complement to reduce the likelihood of biliary injuries (NCT01881399).

Postoperative complications as an independent risk factor for recurrence after laparoscopic ventral hernia repair: a prospective study of 417 patients with long-term follow-up.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) has become widely used. This study evaluates outcomes of LVHR, with particular reference to complications, seromas, and long-term recurrence. METHODS: A review of a prospective database of consecutive patients undergoing LVHR with intraperitoneal onlay mesh (IPOM) was performed at a single institution. Patient's characteristics, surgical procedures, and postoperative outcomes were analyzed and related to long-term recurrence. RESULTS: From 2005 to 2014, 417 patients underwent LVHR. Mean age and body mass index (BMI) were 54 years and 31 kg/m2. Mesh fixation was carried out with transfascial sutures, completed with absorbable tacks (72 %), metal tacks (24 %), or intraperitoneal sutures (4 %). Intraoperative complications occurred in three patients. Overall morbidity included 8.25 % of minor complications and 2.5 % of major complications without mortality. The overall recurrence rate was 9.8 %. Median time for recurrence was 15.3 months (3-72) and median follow-up was 31.6 months (8-119). In a multivariate analysis, previous interventions (OR 1.44; CI 1.15-1.79; p = 0.01), postoperative complications (OR 2.57; CI 1.09-6.03; p = 0.03), and Clavien-Dindo score >2 (OR 1.43; CI 1.031-1.876; p = 0.02) appeared as independent prognostic factors of recurrence. Minor complications were associated with 14.7 % of recurrence and major complications with 30 % of recurrence. Emergency LVHR (6 %) did not increase the rate of complications. Overall seroma rate was 18.7 %, with 1.4 % of persisting or complicated seroma. BMI (OR 1.05; CI 1.01-1.08; p = 0.026) and vascular surgery history (OR 5.74; CI 2.11-15.58; p < 0.001) were independent predictive factors for seroma. Recurrence did not appear to be related to seroma. CONCLUSION: LVHR combines the benefits of laparoscopy with those of mesh repair. Seroma formation should no longer be considered as a complication. It is spontaneously regressive in most cases. Postoperative complications and their degree of severity appear to be independent prognostic factors for recurrence, which can be limited with a standardized technique and may make IPOM-LVHR a reference procedure.

Novel laparoscopic narrow band imaging for real-time detection of bile leak during hepatectomy: proof of the concept in a porcine model.

INTRODUCTION: Bile leakage is a serious complication occurring in up to 10 % of hepatic resections. Intraoperative detection of bile leakage is challenging, and concomitant blood oozing can mask the presence of bile. Intraductal dye injection [methylene blue or indocyanine green (ICG)] is a validated technique to detect bile leakage. However, this method is time-consuming, particularly in the laparoscopic setting. A novel narrow band imaging (NBI) modality (SPECTRA-A; Karl Storz, Tuttlingen, Germany) allows easy discrimination of the presence of bile, which appears in clear orange, by image processing. The aim of this experimental study was to evaluate SPECTRA-A ability to detect bile leakage. METHODS: Twelve laparoscopic partial hepatectomies were performed in seven pigs. The common bile duct was clipped distally and dissected, and a catheter was inserted and secured with a suture or a clip. Liver dissection was achieved with an ultrasonic cutting device. Dissection surfaces were checked by frequently switching on the SPECTRA filter to identify the presence of bile leakage. Intraductal ICG injection through the catheter was performed to confirm SPECTRA findings. RESULTS: Three active bile leakages were obtained out of 12 hepatectomies and successfully detected intraoperatively by the SPECTRA. There was complete concordance between NBI and ICG fluorescence detection. No active leaks were found in the remaining cases with both techniques. The leaking area identified was sutured, and SPECTRA was used to assess the success of the repair. CONCLUSIONS: The SPECTRA laparoscopic image processing system allows for rapid detection of bile leaks following hepatectomy without any contrast injection.

Esophageal covered stent fixation using an endoscopic over-the-scope clip. Mechanical proof of the concept and first clinical experience.

BACKGROUND AND STUDY AIMS: Endoscopic suturing reduces stent migration, but is challenging and time-consuming. We compare endoscopic suturing versus anchoring with a novel over-the-scope clip (Padlock) to fix esophageal stents. Additionally, the first clinical case of Padlock stent fixation is reported. MATERIALS AND METHODS: A fully covered esophageal stent was placed in 11 pigs and fixed with one figure-of-eight suture (n = 5) or with a Padlock (n = 4) or not fixed (controls; n = 2). The force required to mobilize the stent was recorded. CLINICAL CASE: an esophageal stent was fixed with a Padlock and endoscopically removed 1 month later, in an 82-year-old patient. RESULTS: Mean force (newton) to mobilize the stent was similar after suturing and Padlock fixation (23.99 ± 14.91 vs. 19.97 ± 7.62; p = 0.32). In controls was 7 and 11 Newtons. Suturing time (seconds) was longer than Padlock application (455.4 ± 144.83 vs. 155 ± 12.9; p = 0.002). CLINICAL CASE: stent fixation was feasible and uncomplicated. Removal was easy, and only mild bleeding occurred. CONCLUSIONS: Padlock is faster than endoscopic suturing and achieves similar stent fixation. The first clinical case confirms the feasibility of the method.

Age impact on weight loss and glycolipid profile after laparoscopic sleeve gastrectomy: experience with 308 consecutive patients.

BACKGROUND: The aim of this study was to evaluate the impact of age on weight loss and on related glycolipid profile changes at 2-year follow-up after laparoscopic sleeve gastrectomy (LSG). METHODS: From 2005 to 2010, a total of 308 consecutive patients undergoing LSG were enrolled. Mean age was 39.7 ± 10.7 years, mean weight was 127.9 ± 24.5 kg, and mean body mass index (BMI) was 45.9 ± 6.8 kg/m(2). Patients were divided into three age groups: young (18-29 years, n = 64), intermediate (30-49 years, n = 183), and senior (50-68 years, n = 61). BMI, excess weight loss (%EWL), and several biochemical examinations for the evaluation of glycolipid profile transition, including homeostasis model assessment for insulin resistance (HOMA-IR), were assessed at 6, 12, and 24 months (M6, M12, and M24) after LSG. RESULTS: All three groups had a significant BMI reduction and %EWL at 2 years' follow-up. The young group obtained significantly better %EWL at M6, M12, and M24 (62.6 ± 14.4, 73.4 ± 17.1, and 72.5 ± 18.9 %) compared to intermediate (53.2 ± 18.0, 64.8 ± 19.9, and 66.8 ± 23.0 %) and senior group (48.0 ± 15.5, 54.6 ± 15.3, and 54.4 ± 15.4 %). Fasting serum glucose levels improved significantly in all three groups at all follow-up assessment points (M6, M12, and M24). A significant improvement in HbA1c was also observed in the three groups at M6 and M12, while at M24 only patients in the young and intermediate groups still presented a significantly improved glycemic control. A significantly lower HOMA-IR improvement was observed at M6 in the senior group (2.83 ± 1.86) compared to both young (1.30 ± 0.54) and intermediate (1.43 ± 0.82) groups of patients. Total and low-density lipoprotein cholesterol level was significantly improved only in the young group. CONCLUSIONS: An age-dependent trend toward better %EWL and glycolipid profile improvement was observed in young patients after LSG.

Impact of Roux-en-Y gastric bypass versus sleeve gastrectomy on vitamin D metabolism: short-term results from a prospective randomized clinical trial.

PURPOSE: To assess postoperative outcomes of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). Short-term results on vitamin D and parathormone (PTH) metabolism are reported. METHODS: One hundred patients were randomly assigned to RYGB (n = 45) or SG (n = 55). Vitamin D, PTH, and calcium were assessed at inclusion and after 1, 3, 6, and 12 months (M1, M3, M6, and M12). Eighty-eight patients completed 1-year follow-up. RESULTS: Mean postoperative excess weight loss (%EWL) at M1, M3, M6, and M12 was 25.39, 43.47, 63.75, and 80.38 % versus 25.25, 51.32, 64.67, and 82.97 % in RYGB and SG, respectively. Vitamin D values were statistically significantly higher after SG compared to RYGB at M3 (61.57 pmol/L, standard deviation [SD] 14.29 vs. 54.81 SD 7.65; p = 0.01) and M12 (59.83 pmol/L, SD 6.41 vs. 56.15 SD 8.18; p = 0.02). Vitamin D deficiency rate decreased from 84.62 to 35 % at M6 (p = 0.04) and 48 % at M12 (p = 0.01) in the SG group, while there was no significant improvement in the RYGB group. Serum parathyroid hormone (sPTH) level was decreased significantly in the SG group by M3 (44.8 ng/L vs. 28.6; p = 0.03), M6 (44.9 ng/L vs. 25.8; p = 0.017), and M12 (41.4 ng/L vs. 20.5; p = 0.017). Secondary hyperparathyroidism rate was 20.83 and 24 % at M1 (p = 1), 16.67 and 8 % at M3 (p = 0.41), 14.29 and 0 % at M6 (p = 0.08), and 15 and 0 % at M12 (p = 0.23) in the RYGB and SG groups, respectively. CONCLUSIONS: Patients after RYGB had a significantly higher postoperative vitamin D deficiency and higher sPTH levels than after SG.

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era.

Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.

Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: a nationwide registry study from the Italian Medicines Agency.

In this analysis we describe the effectiveness of first-line ibrutinib in 747 patients with chronic lymphocytic leukemia (CLL) and TP53 aberrations in a nationwide study with a 100% capture of patients who received the study drug. Median age was 71 years (range 32-95). An estimated treatment persistence rate of 63.4% (95% CI 60.0%-67.0%) and survival rate of 82.6% (95% CI 79.9-85.4%) were recorded at 24 months. Disease progression or death were the reasons for discontinuation in 182/397 patients (45.8%). A higher risk of treatment discontinuation was found to be associated with age, ECOG-PS and pre-existing heart disease, whereas ECOG ≥ 1, age ≥ 70 years and male sex were associated with an increased risk of death. Median post-progression overall survival (OS) was 12.2 months (95% CI 9.2-22.0). Post-discontinuation median OS in patients who discontinued ibrutinib for other reasons was not reached (95% CI 42.3 months - NA). Ibrutinib was an effective first-line treatment for CLL and TP53 aberrations in patients treated at large academic centers and community practice hospitals. Clinical characteristics at baseline may influence the effectiveness of ibrutinib, whereas the experience of prescribing centers and multi-hit or single-hit TP53 aberrations had no impact on outcome in this high-risk population.

Laparoscopy-assisted vs open total gastrectomy with D2 lymphadenectomy for advanced gastric cancer: results of a retrospective, multicenter study.

The aim of this study was to retrospectively compare the results of laparoscopy-assisted total gastrectomy (LATG) with those of open total gastrectomy (OTG) for advanced gastric cancer. Patients undergoing total gastrectomy for a T4a, N0-3a-b, M0 gastric adenocarcinoma were divided into two groups. Patients in group A (n = 122) underwent LAG, whereas patients in group B (n = 109) underwent OTG. Mean length of follow-up was 39 months. Primary study's endpoints were postoperative mortality and morbidity, overall late survival (OS) and disease-free survival (DFS). Secondary endpoints were the number of retrieved lymph nodes, operating time, intraoperative blood loss, postoperative length of stay (LOS) and the incidence of local recurrence. Twenty-four patients in group A (19.6%) required conversion into OTG. Postoperative mortality was absent in both groups. Postoperative morbidity was 19% in group A and 11% in group B [p = 0.19]. OS was 34% in group A and 42% in group B [p = 0.21]. DFS was 29% in group A and 33% in group B [p = 0.49]. Mean number of retrieved lymph nodes was 29 in group A and 34 in group B [p < 0.01]. Mean intraoperative blood loss was 230 ml in group A and 180 ml in group B [p = 0.02]. Mean postoperative LOS was 9 days in group A and 11 days in group B [p = 0.09]. Local recurrence was 19% in group A and 13% in group B [p = 0.20]. For advanced gastric cancer, OTG favorably compares with LATG.

BL-MOL-AR Project, Preliminary Results about Liquid Biopsy: Molecular Approach Experience and Research Activity in Oncological Settings.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.