An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Protective ileostomy creation after anterior resection of the rectum: Shared decision-making or still subjective?

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.

Long splenic flexure carcinoma requiring laparoscopic extended left hemicolectomy with CME and transverse-rectal anastomosis: technique for a modified partial Deloyers in 5 steps to achieve enough reach and preserving middle colic vessels.

INTRODUCTION: This How-I-Do-It article presents a modified Deloyers procedure by mean of the case of a 67-year-old female with adenocarcinoma extending for a long segment and involving the splenic flexure and proximal descending colon who underwent a laparoscopic left extended hemicolectomy (LELC) with derotation of the right colon and primary colorectal anastomosis. BACKGROUND: While laparoscopic extended right colectomy is a well-established procedure, LELC is rarely used (mainly for distal transverse or proximal descending colon carcinomas extending to the area of the splenic flexure). LELC presents several technical challenges which are demonstrated in this How-I-Do-It article. TECHNIQUE AND METHODS: Firstly, the steps needed to mobilize the left colon and procure a safe approach to the splenic flexure are described, especially when a tumor is closely related to it. This is achieved by mobilization and resection of the descending colon, while maintaining a complete mesocolic excision to the level of the duodenojejunal ligament for the inferior mesenteric vein and flush to the aorta for the inferior mesenteric artery. Subsequently, we depict the adjuvant steps required to enable a primary anastomosis by trying to mobilize the transverse colon and release as much of the mesocolic attachments at the splenic flexure area. Finally, we present the rare instance when a laparoscopic derotation of the ascending colon is required to provide a tension-free anastomosis. The resection is completed by delivery of the fully derotated ascending colon and hepatic flexure through a suprapubic mini-Pfannenstiel incision. The primary colorectal anastomosis is subsequently fashioned in a tension-free way and provides for a quick postoperative recovery of the patient. RESULTS: This modified Deloyers procedure preserves the middle colic since the fully mobilized mesocolon allows for a tension-free anastomosis while maintaining better blood supply to the mobilized stump. Also, by eliminating the need for a mesenteric window and the transposition of the caecum, we allow the small bowel to rest over the anastomosis and the mobilized transverse colon and reduce the possibility of an internal herniation of the small bowel into the mesentery. CONCLUSIONS: Laparoscopic derotation of the right colon and a partial, modified Deloyers procedure preserving the middle colic vessels are feasible techniques in experienced hands to provide primary anastomosis after LELC with improved functional outcome. Nevertheless, it is important to consider anatomical aspects of the left hemicolectomy along with oncological considerations, to provide both a safe oncological resection along with good postoperative bowel function.

HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy.

The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson's coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson's coefficients between -0.47 and -0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1-35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1-41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.

Outcome of laparoscopic ventral mesh rectopexy for full-thickness external rectal prolapse: a systematic review, meta-analysis, and meta-regression analysis of the predictors for recurrence.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) has proved effective in the treatment of internal and external rectal prolapse. The present meta-analysis aimed to determine the predictive factors of recurrence of full-thickness external rectal prolapse after LVMR. METHODS: An organized, systematic search of electronic databases including PubMed/Medline, Embase, Scopus, and Cochran library was conducted in adherence to PRISMA guidelines. Studies that reported the outcome of LVMR in patients with full-thickness external rectal prolapse were included according to predefined criteria. A meta-regression analysis and sub-group meta-analyses were performed to recognize the patient and technical factors that were associated with higher recurrence rates. RESULTS: Seventeen studies comprising 1242 patients of a median age of 60 years were included. The median operation time was 122.3 min. Conversion to open surgery was required in 22 (1.8%) patients. The weighted mean complication rate across the studies was 12.4% (95% CI 8.4-16.4) and the weighted mean rate of recurrence of full-thickness external rectal prolapse was 2.8% (95% CI 1.4-4.3). The median follow-up duration was 23 months. Male gender (SE = 0.018, p = 0.008) and length of the mesh (SE = - 0.007, p = 0.025) were significantly associated with full-thickness recurrence of rectal prolapse. The weighted mean rates of improvement in fecal incontinence and constipation after LVMR were 79.3% and 71%, respectively. CONCLUSION: LVMR is an effective and safe option in treatment of full-thickness external rectal prolapse with low recurrence and complication rates. Male patients and length of the mesh may potentially have a significant impact on recurrence of rectal prolapse after LVMR.

Correction to: Outcomes after rectosigmoid resection for endometriosis: a systematic literature review.

The authors of the published version of this article missed to add the second affiliation of Mostafa Shalaby. The new affiliation is now added and presented correctly in this article. The remainder of the article remains unchanged.

Outcomes after rectosigmoid resection for endometriosis: a systematic literature review.

PURPOSE: "Endometriosis" is defined such as the presence of endometrial glands and stroma outside the uterine cavity. This ectopic condition may develop as deeply infiltrating endometriosis (DIE) when a solid mass is located deeper than 5 mm underneath the peritoneum including the intestinal wall. The ideal surgical treatment is still under search, and treatment may range from simple shaving to rectal resection. The aim of the present systematic review is to report and analyze the postoperative outcomes after rectosigmoid resection for endometriosis. METHODS: We performed a systematic review according to Meta-analysis of Observational Studies in Epidemiology guidelines. The search was carried out in the PubMed database, using the keywords: "rectal resection" AND "endometriosis" and "rectosigmoid resection" AND "endometriosis." The search revealed 380 papers of which 78 were fully analyzed. RESULTS: Thirty-eight articles published between 1998 and 2017 were included. Three thousand seventy-nine patients (mean age 34.28 ± 2.46) were included. Laparoscopic approach was the most employed (90.3%) followed by the open one (7.9%) and the robotic one (1.7%). Overall operative time was 238.47 ± 66.82. Conversion rate was 2.7%. In more than 80% of cases, associated procedures were performed. Intraoperative complications were observed in 1% of cases. The overall postoperative complications rate was 18.5% (571 patients), and the most frequent complication was recto-vaginal fistula (74 patients, 2.4%). Postoperative mortality rate was 0.03% and mean hospital stay was 8.88 ± 3.71 days. CONCLUSIONS: Despite the large and extremely various number of associated procedures, rectosigmoid resection is a feasible and safe technique to treat endometriosis.

Correction to: Interstitial cells of Cajal increased in patients with rectal prolapse.

The authors of the published version of this article missed to add the second affiliation of Mostafa Shalaby. The new affiliation is now added and presented correctly in this article. The remainder of the article remains unchanged.

Endoscopic pilonidal sinus treatment: a systematic review and meta-analysis.

BACKGROUND: Sacrococcygeal pilonidal disease (SPD) is a common surgical condition for which a multitude of surgical treatments have been described. The present review aimed to evaluate the efficacy and safety of a novel endoscopic procedure for the treatment of SPD. METHODS: An organized literature search was conducted. Electronic databases including PubMed/Medline, Scopus, Embase, and Cochrane library were searched for articles that assessed the endoscopic treatment for SPD. The main outcome parameters were failure of the technique including persistence and recurrence of SPD, postoperative complications and pain, time to complete healing, and time to return to work. RESULTS: Nine studies with a total of 497 patients were included. Mean age of patients was 24.8 years. Mean operation time was 34.7 min. The procedure was performed as day-case surgery in all studies. The mean Visual analogue score of pain within the first week was 1.35. Failure of the technique was recorded in 40 (8.04%) patients, 20 (4.02%) had persistent SPD and 20 (4.02%) developed recurrence. The weighted mean failure rate of the technique was 6.3% (95% CI 3.6-9.1). Mean weighted complication rate was 1.1% (95% CI 0.3-2.4). Mean time to complete healing was 32.9 days and mean time to return to work was 2.9 days. CONCLUSION: The endoscopic treatment of pilonidal sinus is a promising and safe method of treatment of SPD. The main advantages of the endoscopic treatment as compared to conventional surgery are the minimal postoperative pain, quick healing, and short time to return to work and daily activities.

Transanal Hemorrhoidal Dearterialization Versus Stapled Hemorrhoidopexy: Long-Term Follow-up of a Prospective Randomized Study.

AIM: This study aims to compare the early and late outcomes of transanal hemorrhoidal dearterialization (THD) versus stapled hemorrhoidopexy (SH) for the treatment of hemorrhoidal disease. METHODS: From January 2013 to December 2014, 100 patients-50 patients on each arm-were randomly allocated to THD or SH groups. The inclusion criteria were grade III and IV hemorrhoids diagnosed by clinical examination and proctoscopy. The primary outcome was to compare the recurrence rate with a minimum follow-up of 2 years, and the secondary outcome was to compare complications rate, time to return to work postsurgery, procedure length, and patient's satisfaction between the 2 techniques. RESULTS: The mean follow-up period was 33.7 ± 7.6. The recurrence rate was 4% in the SH group and 16% in the THD group ( P = .04). There was no difference in the intraoperative and postoperative complications rate; the pain score was significantly higher in the THD group. The mean operative time was significantly shorter in the SH group compared with the THD group. Patients in the THD group returned to work or routine activities significantly later compared with patients in the SH group. The overall satisfaction rate was also higher in the SH group. CONCLUSION: Both procedures are simple and easy to perform for the treatment of grade III and IV hemorrhoids. SH showed better results in terms of lower rate of recurrence, lower postoperative pain, quicker return to work, and higher patient satisfaction.

Sensitivity and specificity of indocyanine green near-infrared fluorescence imaging in detection of metastatic lymph nodes in colorectal cancer: Systematic review and meta-analysis.

This review aimed to determine the overall sensitivity and specificity of indocyanine green (ICG) near-infrared (NIR) fluorescence in sentinel lymph node (SLN) detection in Colorectal cancer (CRC). A systematic search in electronic databases was conducted. Twelve studies including 248 patients were reviewed. The median sensitivity, specificity, and accuracy rates were 73.7, 100, and 75.7. The pooled sensitivity and specificity rates were 71% and 84.6%. In conclusion, ICG-NIR fluorescence is a promising technique for detecting SLNs in CRC.

Radiofrequency-Based Identification Medical Device: An Evaluable Solution for Surgical Sponge Retrieval?

BACKGROUND: A retained surgical item in patients (gossypiboma) is a persisting problem, despite consistent improvements and existing guidelines in counting instruments and sponges. Previous experiences with radiofrequency identification technology (RFID) tracking sponges show that it could represent an innovation, in order to reduce the criticism and increase the effectiveness during surgical procedures. We present an automated system that allows reduction of errors and improves safety in the operating room. METHODS: The system consists of 3 antennas, surgical sponges containing RFID tags, and dedicated software applications, with Wi-Fi real-time communication between devices. The first antenna provides the initial count of gauzes; the second a real-time counting during surgery, including the sponges thrown into the kick-bucket; and the third can be used in the event of uneven sponge count. The software allows management at all stages of the process. RESULTS: In vitro and in vivo tests were performed: the system provided excellent results in detecting sponges in patients' body. Hundred percent retained sponges were detected correctly, even when they were overlapped. No false positive or false negative was recorded. The counting procedure turned out to be more streamlined and efficient and it could save time in a standard procedure. CONCLUSIONS: The RFID system for sponge tracking was shown to be experimentally a reliable and feasible method to track sponges with a full detection accuracy in the operating room. The results indicate the system to be safe and effective with acceptable cost-effective parameters.

Transanal Inspection and Management of Low Colorectal Anastomosis Performed With a New Technique: the TICRANT Study.

BACKGROUND: Anastomotic leakage is one of the most serious complications after rectal cancer surgery. METHOD: A prospective multicenter interventional study to assess a newly described technique of creating the colorectal and coloanal anastomosis. The primary outcome was to access the safety and efficacy of this technique in the reduction of anastomotic leak. RESULT: Fifty-three patients with rectal cancer who underwent low or ultra-low anterior resection were included in the study. There were 35 males and 18 females, with a median age of 68 years (range = 49-89 years). The median tumor distance from the anal verge was 8 cm (range = 4-12 cm), and the median body mass index was 24 kg/m2 (range = 20-35 kg/m2). Thirty patients underwent open, 16 laparoscopic, and 7 robotic surgeries. Multiple firing (2-charges) was required in 30 patients to obtain a complete rectal division. Forty-five patients had colorectal anastomosis, and 8 patients had coloanal anastomosis. The protective ileostomy was created in 40 patients at the time of initial surgery. There was no mortality in the first 30 days postoperatively, and only 10 (19%) patients developed complications. There were 3 anastomotic leakages (6%); 2 of them were subclinical with ileostomy created at initial operation and both were treated conservatively with transanal drainage and intravenous antibiotics. One patient required reoperation and ileostomy. The median length of hospital stay was 10 days (range = 4-20 days). CONCLUSION: Our technique is a safe and efficient method of creation of colorectal anastomosis. It is also a universal method that can be used in open, laparoscopic, and robotic surgeries.

Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.

BACKGROUND: NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC. METHODS: Using polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs). RESULTS: The allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano's CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)]. CONCLUSIONS: Our data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.

Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities.

In both Crohn's disease (CD) and ulcerative colitis (UC), the gut is massively infiltrated with B cells and plasma cells, but the role of these cell types in the pathogenesis of gut tissue damage remains largely unknown. Human B cells express granzyme B (GrB) when cultured with IL-21, a cytokine overproduced in CD and UC mucosa. We therefore examined whether mucosal B cells express GrB and have cytotoxic activity in inflammatory bowel disease (IBD). GrB-expressing CD19(+) and IgA(+) cells were seen in the normal intestinal mucosa, but they were significantly more frequent in both CD and UC. In contrast, only a minority of CD19(+) and IgA(+) cells expressed perforin with no difference between IBD and controls. GrB-producing CD19(+) cells expressed CD27 and were CD38(high) and CD20 negative. CD19(+) B cells from IBD patients induced HCT-116 cell death. IL-21 enhanced GrB expression in control CD19(+) B cells and increased their cytotoxic activity. These data indicate that IBD-related inflammation is marked by mucosal accumulation of cytotoxic, GrB-expressing CD19(+) and IgA(+) cells, suggesting a role for these cells in IBD-associated epithelial damage.

HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.

Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients.

BACKGROUND: Tumor associated antigens are useful in colorectal cancer (CRC) management. The ribosomal P proteins (P0, P1, P2) play an important role in protein synthesis and tumor formation. The immunogenicity of the ribosomal P0 protein in head and neck, in breast and prostate cancer patients and the overexpression of the carboxyl-terminal P0 epitope (C-22 P0) in some tumors were reported. METHODS: Sera from 72 colorectal tumor patients (67 malignant and 5 benign tumors) were compared with 73 healthy donor sera for the presence of antibodies to CEA, EGFR, ErbB2 and ribosomal P proteins by western blotting or ELISA. Expression of the C-22 P0 epitope on tissues and colon cancer cells was determined by immunoperoxidase staining and indirect immunofluorescence/western blotting, respectively, employing MAb 2B2. Biological effects of MAb 2B2 on colon cancer cells were assessed by the Sulforhodamine B cell proliferation assay, trypan blue exclusion test and cleaved caspase-3 detection. Fisher's exact test was used to compare the number of auto-antibodies positive patients with healthy donors. Variation in the C-22 P0 expression, and in the number of apoptotic cells was evaluated by Student's t-test. Variation in cell survival and cell death was evaluated by Newman-Keuls test. RESULTS: No significant humoral response was observed to CEA, EGFR and ErbB2 in CRC patients. Conversely, 7 out of 67 CRC patient sera reacted to ribosomal P proteins. The prevalence of P proteins auto-antibodies in CRC patients was significant. Five patients showed restricted P0 immunoreactivity, while two patients reacted simultaneously to all P proteins. The C-22 P0 epitope was homogenously expressed both in malignant tumors and the adjacent mucosa, but the intensity of expression was higher in the tumor. Starved colon cancer cells showed a higher C-22 P0 epitope plasma membrane expression compared to control cells. MAb 2B2 inhibited colon cancer cell growth and induced cell death in a dose dependent manner. CONCLUSIONS: Our study shows a spontaneous humoral immune response to ribosomal P0 protein in CRC patients and the inhibition of in vitro cancer cell growth after C-22 P0 epitope targeting. The ribosomal P0 protein might be a useful immunological target in CRC patients.