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.

The role of nutraceutical medications in men with non bacterial chronic prostatitis and chronic pelvic pain syndrome: A prospective non blinded study utilizing flower pollen extracts versus bioflavonoids.

INTRODUCTION: Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) represents a challenge for the urologist, since the therapeutic efficacy does not always result in a satisfactory quality of life for the patients. Often the side effects of the medications used (antiinflammatories, antibiotics, alpha blockers) far outweighs the benefits gained with their admission. The choice of nutraceutical medications is preferred for their effectiveness, that has been accepted and proven by the scientific community, and for the low incidence of side effects. The objective of this study to compare the therapeutic efficacy of the flower pollen extracts (Deprox®) versus Bioflavonoids in terms of reduction of symptoms, and in the average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and to evaluate the quality of life improvement of the patients affected by CP/CPPS. METHODS: Among the 68 patients presented with prostatic symptoms to the Hospital "Umberto I" in Rome, Italy between March 2016 and June 2016, 54 patients met the clinical diagnosis of CP/CPPS (class IIIa or IIIb according to the NIH classification). The patients were assigned to either treatment with Deprox® or quercetin based on a randomization scheme previously determined.The NIH- CPSI, IPSS, QoL questionnaires were administered. Every patient underwent bacterial cultures and trans-rectal ultrasound. RESULTS: There was a statistically significant improvement of the NIH-CPSI score and QoL in the Deprox® group (p = < 0.0001 and p = 0.003 respectively). The average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was statistically significant (p = 0.0019). In the absence of efficacy of the "conventional" medications, which also carries significant side effects, the dietary supplements may represent a valid alternative. CONCLUSIONS: DEPROX® has demonstrated a significant improvement of the symptoms and quality of life of patients diagnosed with by CP/CPPS. Furthermore, there was a statistical difference in the average waiting time of the variation of the NIH-CPSI) score without side effects as compared to the bioflavonoids complex with quercetin.

Advanced chondrosarcoma of the pelvis: A rare case of urinary obstruction.

Chondrosarcoma is the second most common malignant tumor of the bone with an incidence of 1 in 200.000 per year. Axial skeleton is frequently involved showing poorer oncological outcomes than appendicular one: human pelvis is a site predilection. It is rarely associated to urinary obstruction but according to its localization, it can be frequently linked to compression of pelvic organs as bladder, prostate or bowel. We describe the case of a 52 years old caucasian male with history of advanced pelvic chondrosarcoma and severe hydronephrosis due to total bladder dislocation.

Total phallic reconstruction after penile amputation for donkey bite: Case report and review of the literature.

There are very few reported cases of traumatic amputation of the male genitalia due to animal bite. The management involves thorough washout of the wounds, debridement, antibiotic prophylaxis, tetanus and rabies immunization followed by immediate reconstruction or primary wound closure with delayed reconstruction, when immediate reconstruction is not feasible. When immediate reconstruction is not feasible, long-term good functional and cosmetic results are still possible in the majority of cases by performing total phallic reconstruction. In particular, it is now possible to fashion a cosmetically acceptable sensate phallus with incorporated neourethra, to allow the patient to void while standing and to ejaculate, and with enough bulk to allow the insertion of a penile prosthesis to guarantee the rigidity necessary to engage in penetrative sexual intercourse.

Malignant priapism due to penile metastases: Case series and literature review.

Malignant priapism secondary to penile metastases is a rare condition. This term was originally used by Peacock in 1938 to describe a condition of painful induration and erection of the penis due to metastatic infiltration by a neoplasm. In the current literature there are 512 case reports. The primary tumor sites are bladder, prostate and rectum. The treatment has only palliative intent and consists of local tumor excision, penectomy, radiotherapy and chemotherapy. We present one case of malignant priapism originated from prostate cancer, and two from urothelial carcinoma of the bladder. Different approaches in diagnosis and therapy were performed. The entire three patient reported a relief of the pain following the treatment, with an improvement of their quality of life, even though it was only temporary as a palliative. Malignant priapism is a rare medical emergency. Penile/pelvis magnetic resonance imaging (MRI) scan and corporal biopsies are considered an effective method of diagnosis of the primary organ site.

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.

Wnt3a/ß-Catenin Signaling Conditions Differentiation of Partially Exhausted T-effector Cells in Human Cancers.

In this study, we investigated the role of the Wnt/ß-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and ß-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+T-bet-phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression. Wnt3a/ß-catenin signaling in T naïve cells in vitro recapitulated the T-cell setting in vivo Indeed, the differentiation of cultured T naïve cells was arrested, producing cells that resembled the EomeshighT-betlowß-cateninhigh T cells with moderate effector functions that infiltrated tumor and nontumor areas. Wnt3a blockade improved the capacity of T naïve cells to differentiate into effector cells in vitro However, Wnt3a blockade did not affect the function and phenotype of differentiated, partially exhausted, tumor-infiltrating T cells ex vivo Taken together, our data suggest that Wnt3a blockade halts the capacity of Wnt/ß-catenin signaling to inhibit the differentiation of T naïve cells, but it does not restore the dysfunction of differentiated T cells, in the tumor setting. Cancer Immunol Res; 6(8); 941-52. ©2018 AACR.

Accuracy of magnetic resonance cholangiography compared to operative endoscopy in detecting biliary stones, a single center experience and review of literature.

AIM: To compare diagnostic sensitivity, specificity and accuracy of magnetic resonance cholangiopancreatography (MRCP) without contrast medium and endoscopic ultrasound (EUS)/endoscopic retrograde cholangiopancreatography (ERCP) for biliary calculi. METHODS: From January 2012 to December 2013, two-hundred-sixty-three patients underwent MRCP at our institution, all MRCP procedure were performed with the same machinery. In two-hundred MRCP was done for pure hepatobiliary symptoms and these patients are the subjects of this study. Among these two-hundred patients, one-hundred-eleven (55.5%) underwent ERCP after MRCP. The retrospective study design consisted in the systematic revision of all images from MRCP and EUS/ERCP performed by two radiologist with a long experience in biliary imaging, an experienced endoscopist and a senior consultant in Hepatobiliopancreatic surgery. A false positive was defined an MRCP showing calculi with no findings at EUS/ERCP; a true positive was defined as a concordance between MRCP and EUS/ERCP findings; a false negative was defined as the absence of images suggesting calculi at MRCP with calculi localization/extraction at EUS/ERCP and a true negative was defined as a patient with no calculi at MRCP ad at least 6 mo of asymptomatic follow-up. Biliary tree dilatation was defined as a common bile duct diameter larger than 6 mm in a patient who had an in situ gallbladder. A third blinded radiologist who examined the MRCP and ERCP data reviewed misdiagnosed cases. Once obtained overall data on sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) we divided patients in two groups composed of those having concordant MRCP and EUS/ERCP (Group A, 72 patients) and those having discordant MRCP and EUS/ERCP (Group B, 20 patients). Dataset comparisons had been made by the Student's t-test and χ (2) when appropriate. RESULTS: Two-hundred patients (91 men, 109 women, mean age 67.6 years, and range 25-98 years) underwent MRCP. All patients attended regular follow-up for at least 6 mo. Morbidity and mortality related to MRCP were null. MRCP was the only exam performed in 89 patients because it did show only calculi into the gallbladder with no signs of the presence of calculi into the bile duct and symptoms resolved within a few days or after colecistectomy. The patients remained asymptomatic for at least 6 mo, and we assumed they were true negatives. One hundred eleven (53 men, 58 women, mean age 69 years, range 25-98 years) underwent ERCP following MRCP. We did not find any difference between the two groups in terms of race, age, and sex. The overall median interval between MRCP and ERCP was 9 d. In detecting biliary stones MRCP Sensitivity was 77.4%, Specificity 100% and Accuracy 80.5% with a PPV of 100% and NPV of 85%; EUS showed 95% sensitivity, 100% specificity, 95.5% accuracy with 100% PPV and 57.1% NPV. The association of EUS with ERCP performed at 100% in all the evaluated parameters. When comparing the two groups, we did not find any statistically significant difference regarding age, sex, and race. Similarly, we did not find any differences regarding the number of extracted stones: 116 stones in Group A (median 2, range 1 to 9) and 27 in Group B (median 2, range 1 to 4). When we compared the size of the extracted stones we found that the patients in Group B had significantly smaller stones: 14.16 ± 8.11 mm in Group A and 5.15 ± 2.09 mm in Group B; 95% confidence interval = 5.89-12.13, standard error = 1.577; P < 0.05. We also found that in Group B there was a significantly higher incidence of stones smaller than 5 mm: 36 in Group A and 18 in Group B, P < 0.05. CONCLUSION: Major finding of the present study is that choledocholithiasis is still under-diagnosed in MRCP. Smaller stones (< 5 mm diameter) are hardly visualized on MRCP.

New "all-in-one" device for mesh plug hernioplasty: the Trabucco repair.

UNLABELLED: Although Mesh Plug Repair (MPR) represents an effective method for the treatment of groin hernia, some criticisms still concern adverse effects related to the plug (shrinkage, chronic pain, migration and erosion). Different mesh and plug devices have been proposed in the past mostly to prevent migration but none of these achieved the same popularity as the cone or flower-shaped plug. Authors hereby present a pilot study with a new tridimensional device, denominated NeT Plug and Patch, that avoids any risk of migration. Results after 12 months follow-up have demonstrated low incidence of postoperative and chronic pain, with both patients and surgeons greatly satisfied. NeT Plug and Patch has proven to achieve a simple and effective repair for primary inguinal hernias. KEY WORDS: Mesh-plug, Plug migration, Trabucco repair.