Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review.

Hemophagocytic inflammatory syndrome (HIS) is a rare form of secondary hemophagocytic lymphohistiocytosis caused by an impaired equilibrium between natural killer and cytotoxic T-cell activity, evolving in hypercytokinemia and multiorgan failure. In the context of inborn errors of immunity, HIS occurrence has been reported in severe combined immunodeficiency (SCID) patients, including two cases of adenosine deaminase deficient-SCID (ADA-SCID). Here we describe two additional pediatric cases of ADA-SCID patients who developed HIS. In the first case, HIS was triggered by infectious complications while the patient was on enzyme replacement therapy; the patient was treated with high-dose corticosteroids and intravenous immunoglobulins with HIS remission. However, the patient required HLA-identical sibling donor hematopoietic stem cell transplantation (HSCT) for a definitive cure of ADA-SCID, without HIS relapse up to 13 years after HSCT. The second patient presented HIS 2 years after hematopoietic stem cell gene therapy (GT), secondarily to Varicella-Zoster vaccination and despite CD4+ and CD8+ lymphocytes' reconstitution in line with other ADA SCID patients treated with GT. The child responded to trilinear immunosuppressive therapy (corticosteroids, Cyclosporine A, Anakinra). We observed the persistence of gene-corrected cells up to 5 years post-GT, without HIS relapse. These new cases of children with HIS, together with those reported in the literature, support the hypothesis that a major dysregulation in the immune system can occur in ADA-SCID patients. Our cases show that early identification of the disease is imperative and that a variable degree of immunosuppression could be an effective treatment while allogeneic HSCT is required only in cases of refractoriness. A deeper knowledge of immunologic patterns contributing to HIS pathogenesis in ADA-SCID patients is desirable, to identify new targeted treatments and ensure patients' long-term recovery.

Wiskott-Aldrich syndrome: Oral findings and microbiota in children and review of the literature.

OBJECTIVE: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency, characterized by micro-thrombocytopenia, recurrent infections, and eczema. This study aims to describe common oral manifestations and evaluate oral microbioma of WAS patients. MATERIAL AND METHODS: In this cohort study, 11 male WAS patients and 16 male healthy controls were evaluated in our Center between 2010 and 2018. Data about clinical history, oral examination, Gingival Index (GI) and Plaque Index (PI) were collected from both groups. Periodontal microbiological flora was evaluated on samples of the gingival sulcus. RESULTS: WAS subjects presented with premature loss of deciduous and permanent teeth, inclusions, eruption disturbance, and significantly worse GI and PI. They also showed a trend toward a higher total bacterial load. Fusobacterium nucleatum, reported to contribute to periodontitis onset, was the most prevalent bacteria, together with Porphyromonas gingivalis and Tannerella forsythia. CONCLUSIONS: Our data suggest that WAS patients are at greater risk of alterations in the oral cavity. The statistically higher incidence of periodontitis and the trend to higher prevalence of potentially pathological bacterial species in our small cohort, that should be confirmed in future in a larger population, underline the importance of dentistry monitoring as part of the multidisciplinary management of WAS patients.

Mild SARS-CoV-2 Infection After Gene Therapy in a Child With Wiskott-Aldrich Syndrome: A Case Report.

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.

Dealing with robot-assisted surgery for rectal cancer: Current status and perspectives.

The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition three-dimensional vision, it translates the surgeon's hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors' centre.

Factors predicting worse prognosis in patients affected by pT3 N0 colon cancer: long-term results of a monocentric series of 137 radically resected patients in a 5-year period.

BACKGROUND AND PURPOSE: For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients. PATIENTS AND METHODS: We retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board. RESULTS: Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5 %) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy. CONCLUSIONS: Histology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.

Impact of robotic surgery on sexual and urinary functions after fully robotic nerve-sparing total mesorectal excision for rectal cancer.

BACKGROUND: Urinary and sexual dysfunctions are recognized complications of rectal cancer surgery. Their incidence after robotic surgery is as yet unknown. The aim of this study was to prospectively evaluate the impact of robotic surgery for rectal cancer on sexual and urinary functions in male and female patients. METHODS AND PROCEDURES: From April 2008 to December 2010, 74 patients undergoing fully robotic resection for rectal cancer were prospectively included in the study. Urinary and sexual dysfunctions affecting quality of life were assessed with specific self-administered questionnaires in all patients undergoing robotic total mesorectal excision (RTME). Results were calculated with validated scoring systems and statistically analyzed. RESULTS: The analyses of the questionnaires completed by the 74 patients who underwent RTME showed that sexual function and general sexual satisfaction decreased significantly 1 month after intervention: 19.1 ± 8.7 versus 11.9 ± 10.2 (P < 0.05) for erectile function and 6.9 ± 2.4 versus 5.3 ± 2.5 (P < 0.05) for general satisfaction in men; 2.6 ± 3.3 versus 0.8 ± 1.4 (P < 0.05) and 2.4 ± 2.5 versus 0.7 ± 1.6 (P < 0.05) for arousal and general satisfaction, respectively, in women. Subsequently, both parameters increased progressively, and 1 year after surgery, the values were comparable to those measured before surgery. Concerning urinary function, the grade of incontinence measured 1 year after the intervention was unchanged for both sexes. CONCLUSIONS: RTME allows for preservation of urinary and sexual functions. This is probably due to the superior movements of the wristed instruments that facilitate fine dissection, coupled with a stable and magnified view that helps in recognizing the inferior hypogastric plexus.

Surgical and pathological outcomes after right hemicolectomy: case-matched study comparing robotic and open surgery.

OBJECTIVE: To compare the surgical and pathological outcomes of patients with right-sided colon cancers operated on by means of open and robotic surgery with extracorporeal anastomosis. METHODS: Thirty-three consecutive patients who underwent robotic right hemicolectomy due to right-sided colon cancer were retrospectively well matched with 102 patients operated on by the open approach. Data were included in a prospectively maintained database. RESULTS: Mean operative time was longer in the robotic group (P < 0.001), 191.7 min (134-250) versus 136.2 (45-240) min in the open group. Estimated intraoperative blood loss was less in the robotic group, which presented a mean of 6.1 ml versus 94.8 ml in the open group (P < 0.001). Despite the similar length of the surgical specimen and number of lymph nodes retrieved between both groups, 15 or more lymph nodes were found in the specimen in 90 out of 102 patients (88.2%) operated on by the open technique versus 33 out of 33 patients (100%) who underwent robotic hemicolectomy (P = 0.038). The median length of postoperative hospital stay was shorter in the robotic group, 5 versus 8 days (P < 0.001). No other statistically significant difference was observed in terms of pathological and postoperative results. CONCLUSIONS: Robotic right hemicolectomy is an oncologically safe and effective procedure. The number of lymph nodes retrieved in the robotic group compared with the open group of our series was more homogeneous, and none of the patients operated on with this technique had a suboptimal lymphadenectomy. Further clinical trials are needed to confirm current evidence and determine whether this can influence the prognosis.