IgG4 subclass antibodies are expressed in alternative Th2 environments featuring high IL-10 expression, including several solid tumors such as melanoma. To induce tolerance, allergen immunotherapy mediates antibody class switching from pro-inflammatory IgE to anti-inflammatory IgG4. We previously reported that IgG4 drives allergic M2 macrophages toward tolerogenic states. Here we assessed the roles of IgG4 and macrophage activation in colorectal cancer (CRC). In this observer-blinded, case-control study, we analyzed total circulating serum IgE, IgG1 and IgG4 levels in CRC (n = 38) patients with (n = 13, TxNxM1) or without (n = 25, TxNxM0) metastasis, and in healthy donors (n = 21). Primary cultures of circulating monocyte-derived macrophages from healthy controls and CRC patients were further evaluated in their responses to stimulation with IgG1 or IgG4. We found higher absolute serum levels of IgG4 in patients with CRC. IgG4 enabled polarization of macrophages derived from CRC patients and healthy controls into alternatively-activated tolerogenic M2b phenotypes. IgG4-stimulated M2 macrophages were characterized by lower surface CD206, CD163, CD14, and CD11b expression and higher CCL-1, IL-10, and IL-6 production. IgG4 was less potent that IgG1 in triggering antibody-dependent cell-mediated phagocytosis (ADCP) of cancer cells. Further, higher z-normalized IgG4/-IgE sera level ratios correlated with the presence of metastasis (p = .0247 and p = .0009, respectively) in CRC patients. High IgG4 in CRC synergizes with macrophages in shaping an immunosuppressive microenvironment and impairs anti-cancer effector cell functions. The shift of serum IgG4/IgE ratios toward enhanced tolerance induction in metastatic disease indicates a role for high IgG4 in disease progression and poor prognostic outcome.

Laparoscopic surgery is considered in the treatment of diverticular fistula for the possible reduction of overall morbidity and complication rate if compared to open surgery. Aim of this review is to assess the possible advantages deriving from a laparoscopic approach in the treatment of diverticular fistulas of the colon. Studies presenting at least 10 adult patients who underwent laparoscopic surgery for sigmoid diverticular fistula were reviewed. Fistula recurrence, reintervention, Hartmann's procedure or proximal diversion, conversion to laparotomy were the outcomes considered. 11 non randomized studies were included. Rates of fistula recurrence (0.8%), early reintervention (30 days) (2%) and need for Hartmann's procedure or proximal diversion (1.4%) did not show significant difference between laparoscopy and open technique. there is still concern about which surgery in complicated diverticulitis should be preferred. Laparoscopic approach has led to less postoperative pain, shorter hospital stay, faster recovery and better cosmetic results. Laparoscopic resection and primary anastomosis is a possible approach to sigmoid fistulas but its advantages in terms of lower mortality rate and postoperative stay after colon resection with primary anastomosis should be interpreted with caution. When there is firm evidence supporting it, it is likely that minimally invasive surgery should become the standard approach for diverticular fistulas, thus achieving adequate exposure and better visualization of the surgical field. The lack of RCTs, the small sample size, the heterogeneity of literature do not allow to draw statistically significant conclusions on the laparoscopic surgery for fistulas despite this approach is considered safe.

We aimed at assessing the stability of candidate reference genes in urine sediments of men subjected to digital rectal examination for suspected prostate cancer (PCa). Two microRNAs (miR-191 and miR-25) and 1 small nucleolar RNA (SNORD48) were assayed in 35 post-DRE urine sediments of men with PCa and in 26 subjects with histologically confirmed benign prostatic hyperplasia (BPH). The stability of candidate reference genes was assessed through BestKeeper algorithm and equivalence test. miR-200b and miR-452 were used to test for the effect of normalization on target genes. Our results proved miR-191 to be the most stable gene, showing the lowest degree of variation and the highest stability value. miR-25 and SNORD48 values fell beyond the cutoff of acceptability. In conclusion, we recommend the use of miR-191 for normalization purposes in post-DRE urine sediments.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, and the absence of symptoms in the early stages makes metastasis more likely and reduces survival. To aid in the early diagnosis of ccRCC, we recently developed a method based on urinary miR-122-5p, miR-1271-5p, and miR-15b-5p levels and three controls. The study here presented aimed to validate the previously published method through its application on an independent cohort. The expression of miRNAs in urine specimens from 28 ccRCC patients and 28 healthy subjects (HSs) of the same sex and age was evaluated by RT-qPCR. Statistical analyses were performed, including the preparation of receiver operating characteristic (ROC) curves. The mean ccRCC diameter in ccRCC patients was 4.2 ± 2.4 mm. Urinary miRNA levels were higher in patients than in HSs. The data were processed using the previously developed algorithm (7p-urinary score), and the area under the curve (AUC) of the algorithm’s ROC curve was 0.81 (p-value = 0.0003), with a sensitivity of 96% and specificity of 65%. Therefore, the 7p-urinary score is a potential tool for the early diagnosis of ccRCC.

The management of metastatic Renal Cell Carcinoma (RCC) has changed dramatically in the last 20 years, and the role of surgery in the immunotherapy’s era is under debate. Metastatic lesions interesting pancreas are infrequent, but those harbouring from RCC have an high incidence. If metachronous resections are not rare, synchronous resection of primary RCC and its pancreatic metastasis is uncommonly reported, and accounts for a bad prognosis. We report the case of a 68 years old woman, who presented hematuria at hospital incoming, with radiological appearance of a 13 cm left renal mass, with a 2.5 cm single pancreatic tail metastasis. Work-up of staging ruled out other distant metastases, urothelial cancer and there was no evidence of inferior vena cava thrombosis. We choose a 5-port trans-peritoneal robotic approach using lazy right lateral decubitus. Synchronous robotic radical nephrectomy and spleen-sparing pancreatic resection was performed. The pancreatic mass was completely enucleated from pancreatic parenchyma using a latero-medial dissection. Peri-operative hemoglobine loss was 2.4 g/dL. Total operative time was 213 min. No post-operative complications were recorded and patient was discharged in 7th post-operative day. Histopathological examination showed a pT2b N0 M1 RCC, Fuhrman grade II, with pancreatic tail metastasis; both, primary and metastatic lesions had the same histological characteristics with negative surgical margins. After 9 months patient had no evidence of disease recurrence at radiological studies. The rationale for surgical removal of disseminated tumor, followed by immunotherapy, includes improving prognosis and enhancing the potential of an immune-mediated response to systemic treatment. A spleen-sparing procedure can adequately preserve post-operative immunologic capabilities. In our experience, the correct assessment of pre-operative imaging data and surgeon skills in robotic surgery seem to play a key role in the success of these procedures. Robotic surgery seems to enhance the possibility to control multiple vessels encountered during dissection. Such a conservative approach may be helpful in future research aimed at uncovering biological features, and also leading to better targeted preventive interventions and more individualized and effective treatments.