Genetically driven CD39 expression shapes human tumor-infiltrating CD8+ T-cell functions.

In our study, we investigated the role of CD39 on tumor-infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T-cell exhaustion, we demonstrated a divergent functional activity in CD39+ CD8+ TILs. On the one hand, CD39+ CD8+ TILs (as compared to their CD39- counterparts) produced significantly lower IFN-γ and IL-2 amounts, expressed higher PD-1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD-1 expression. Therefore, CD39+ CD8+ TILs, including those co-expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39-related ATPases improved CD39+ CD8+ T-cell effector function ex vivo, and that CD39+ CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+ CD8+ T-cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs.

Organ-saving surgery for rectal cancer after neoadjuvant chemoradiation: Analysis of failures and long-term results.

BACKGROUND: To analyze long-term results and risk of relapse in the clinical TNM stages II and III, mid-low rectal cancer patients (RC pts), treated with transanal local excision (LE) after major response to neoadjuvant chemoradiation (n-CRT). METHODS: Thirty-two out of 345 extraperitoneal cT3-4 or N+ RC pts (9.3%) underwent LE. INCLUSION CRITERIA: extraperitoneal RC, adenocarcinoma, ECOG Performance Status ≤2. Pts with distant metastases were excluded. RESULTS: All pts showed histologically clear margins of resection and 81.2% were restaged ypT0/mic/1. Nine out of 32 (28.1%) pts relapsed: 7 (21.8%) showed a local recurrence, of which 5 (15.6%) at the endorectal suture, 1 (3.1%) pelvic and 1 (3.1%) mesorectal. Two pts (6.2%) relapsed distantly. Among the pT0/1, 11.5% relapsed vs 100% of the pT2 and pT4 ones. The six pts relapsing locally or in the mesorectal fat underwent a salvage total mesorectal excision surgery. The old patient with pelvic recurrence relapsed after 108 months and underwent a re-irradiation; the two pts with distant metastases were treated with chemotherapy followed by radical surgery. CONCLUSIONS: Presently combined approach seems a valid option in major responders, confirming its potential curative impact in the ypT0/mic/1 pts. A strict selection of pts is basic to obtain favourable results.

Laparoscopic Liver Surgery: What Are the Advantages in Patients with Cirrhosis and Portal Hypertension? Systematic Review and Meta-Analysis with Personal Experience.

Background: Laparoscopic surgery is a choice of treatment for liver diseases; it can decrease postoperative morbidity and length of hospital stay (LOS). Hepatocellular carcinoma (HCC) in patients with cirrhosis and portal hypertension may benefit from minimally invasive liver resections (MILRs) instead of open liver resections (OLRs). Whether minimally invasive approaches are superior to conventional ones is still a matter of debate. We thus aimed to gather the available literature on this specific topic to achieve greater clarity. Materials and Methods: PubMed, EMBASE and Web of Sciences databases were assessed for studies comparing OLRs versus MILRs for HCC in cirrhotic patients up to February 2020. Data from our surgical experience from June 2010 to February 2020 were also included. Demographic characteristics, liver function, the presence of portal hypertension, tumor number, and tumor size and location were assessed; operative time, need for Pringle maneuver, estimated blood loss (EBL), major or minor hepatectomy performance, and conversion rate were evaluated for operative findings. Postoperative outcomes and liver-related complications, surgical site infection (SSI) rate, blood transfusion (BT) rate, need for reintervention, LOS, in-hospital or 30-day mortality, and radicality of resection were also considered. Meta-analysis was performed employing Review Manager 5.3 software. Results: One thousand three hundred twenty-one patients from 13 studies and our own series were considered in the meta-analysis. At preoperative settings, the OLR and MILR groups differed significantly only by tumor size (4.4 versus 3.0, P = .006). Laparoscopic procedures resulted significantly faster (120.32-330 minutes versus 146.8-342.75 minutes, P = .002) and with lower EBL than open ones (88-483 mL versus 200-580 mL, P < .00001), thus requiring less BTs (7.9% versus 13.2%, P = .02). In terms of overall morbidity, minimally invasive surgeries resulted significantly favorable (19.32% versus 38.04%, P < .00001), as well as for ascites (2.7% versus 12.9% P < .00001), postoperative liver failure (7.51% versus 13.61% P = .009), and SSI (1.8% versus 5.42%, P = .002). Accordingly, patients who had undergone MILRs had significantly shorter postoperative hospitalization than patients who underwent conventional open surgery (2.4-36 days versus 4.2-19 days P < .00001). Both groups did not differ in terms of mortality rate and radicality of resection (OLR 93.8% versus 96.1% laparoscopic liver resection, P = .12). Conclusions: Based on the available evidence in the literature, laparoscopic resections rather than open liver ones for HCC surgery in cirrhotic patients seem to reduce postoperative overall morbidity, liver-specific complications, and LOS. The lack of randomized studies on this topic precludes the possibility of achieving defining statements.

Primary leiomyoma of the liver in an immunocompetent patient.

Primary leiomyoma of the liver (PLL) is a rare benign tumor occurring in immunosuppressed people. From 1926 less than fifty cases are reported in the scientific literature and about half are in immunocompetent patients. Etiology of this kind of lesion is not yet well known. We report a case of primary hepatic leiomyoma in a 60-year-old immunocompetent woman. The patient presented with lipothymia with unexpected vomiting. She underwent an ultrasound (US), and a computed tomography (CT) scan that revealed the presence of a single, solid lesion about 9 cm located between the S5 and S8 segment of the liver. It showed a well-defined, heterogeneous hypodensity with internal and peripheral enhancement and various central hypoattenuating areas and no wash-out in the portal and the late phases. Because of her symptoms and the risk of malignancy, the patient underwent a surgical liver resection. Histological diagnosis was primary leiomyoma of the liver. The patient had an uneventful recovery and was discharged after 7 days. At 30 months follow-up there were no symptoms and no evidence of disease. Leiomyoma of the liver is a rare benign neoplasm of which clinical symptoms are nonspecific and the exact radiological diagnosis still remains a challenge for radiologists. Etiology is still unclear and usually PLL represents an incidental diagnosis. Surgery plays a primary role not only in the treatment algorithm, but also in the diagnostic workout.

Robotic Liver Resections: Application of Difficulty Score Systems to an Initial Experience. Is a Specific Robotic Difficulty Score Necessary?

Background: Recently, the minimally invasive surgical approach has been available for performing liver resections (LRs) with laparoscopic and robotic techniques. The robotic approach for LRs seems to overcome several laparoscopic limitations, which is a valid alternative when performed in high volume and specialized centers. Laparoscopic difficulty score systems (DSSs) should serve to guide the surgeon's choice in the best surgical approach to adopt for every single patient, giving the possibility to switch to the open approach when needed. To this day, no specific robotic difficulty scores exist. The aim of our study was to verify the feasibility of applying these scores and related updates on robotic LRs performed in our Institute. Materials and Methods: Out of a total of 683 LRs performed from June 2010 to July 2019, 60 were performed through using a mini invasive approach and of these 18 were performed robotically. The Ban DSS and subsequently the modified Iwate DSS were applied to our cases. Results: Based on our findings, applying the DSS we divided our series into two groups: a low difficulty level group (1-3) made up of 5 patients, and an intermediate difficulty level group (4-6) consisting of 13 patients. Average Ban DSS and subsequently updated score system results were 4.6 ± 1.5 points (range 2-6) for both scores. Conclusions: Difficulties were encountered in applying the score when simultaneous multiple wedge resections were performed. The laparoscopic DSS is applicable to robotic LRs with some limitations due to the peculiarity of the two different minimally invasive approaches. A specific robotic difficulty rating score could be necessary to include these elements.