Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population.

BACKGROUND: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. METHODS: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. RESULTS: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27-3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03-5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45-9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22-1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27-5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45-1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52-5.93) and an AP of 52%. CONCLUSION: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies

Reconstruction Techniques and Associated Morbidity in Minimally Invasive Gastrectomy for Cancer Insights From the GastroBenchmark and GASTRODATA databases

Objective/Background: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. Methods: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed in 2017–2021 in 43 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. Results: Three major anastomotic techniques [circular stapled (CS); linear stapled (LS); and hand sewn (HS)], and 3 major bowel reconstruction types [Roux (RX); Billroth I (BI); Billroth II (BII)] were identified in miTG (n = 878) and miDG (n = 3334). Postoperative complications, including AL (5.2% vs 1.1%), overall (28.7% vs 16.3%), and major morbidity (15.7% vs 8.2%), as well as 90-day mortality (1.6% vs 0.5%) were higher after miTG compared with miDG. After miTG, the AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, and HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as a predictive factor for AL, overall, and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, and RX 1.2%), overall (BI: 14.5%, BII: 15.0%, and RX: 18.7%), and major morbidity (BI: 7.9%, BII: 9.1%, and RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, and RY: 1.1%%) were not affected by bowel reconstruction. Conclusions: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to the surgeon’s preference

Prevalence of Defaecatory Disorders in Morbidly Obese Patients Before and After Bariatric Surgery

BACKGROUND: The prevalence of obesity is increasing worldwide and has lately reached epidemic proportions in western countries. Several epidemiological studies have consistently shown that both overweight and obesity are important risk factors for the development of various functional defaecatory disorders (DDs), including faecal incontinence and constipation. However, data on their prevalence as well as effectiveness of bariatric surgery on their correction are scant. The primary objective of this study was to estimate the effect of morbid obesity on DDs in a cohort of patients listed for bariatric surgery. We also evaluated preliminary results of the effects of sleeve gastrectomy on these disorders. PATIENTS AND METHODS: A questionnaire-based study was proposed to morbidly obese patients having bariatric surgery. Data included demographics, past medical, surgical and obstetrics histories, as well as obesity related co-morbidities. Wexner Constipation Score (WCS) and the Faecal Incontinence Severity Index (FISI) questionnaires were used to evaluate constipation and incontinence. For the purpose of this study, we considered clinically relevant a WCS ≥5 and a FISI score ≥10. The same questionnaires were completed at 3 and 6 months follow-up after surgery. RESULTS: A total of 139 patients accepted the study and 68 underwent sleeve gastrectomy and fully satisfied our inclusion criteria with a minimum follow-up of 6 months. Overall, mean body mass index (BMI) at listing was 47 ± 7 kg/m(2) (range 35-67 kg/m(2)). Mean WCS was 4.1 ± 4 (range 0-17), while mean FISI score (expressed as mean±standard deviation) was 9.5 ± 9 (range 0-38). Overall, 58.9% of the patients reported DDs according to the above-mentioned scores. Twenty-eight patients (20%) had WCS ≥5. Thirty-five patients (25%) had a FISI ≥10 while 19 patients (13.7%) reported combined abnormal scores. Overall, DDs were more evident with the increase of obesity grade: Mean BMI decreased significantly from 47 ± 7 to 36 ± 6 and to 29 ± 4 kg/m(2) respectively at 3 and 6 months after surgery (p < 0.0001). According to the BMI decrease, the mean WCS decreased from 3.7 ± 3 to 3.1 ± 4 and to 1.6 ± 3 respectively at 3 and 6 months (p = 0.02). Similarly, the FISI score decreased from 10 ± 8 to 3 ± 4 and to 1 ± 2 respectively at 3 and 6 months (p = 0.0001). CONCLUSIONS: Defaecatory disorders are common in morbidly obese patients. The risk of DDs increases with BMI. Bariatric surgery reduces DDs, mainly faecal incontinence, and these findings correlated with BMI reduction

Safety and efficacy of totally minimally invasive right colectomy in the obese patients: a multicenter propensity score-matched analysis

Despite the well-known benefits of the minimally invasive approach for the right colon cancer treatment, less is known about its feasibility and advantages in morbid obese patients. The aim of this study is to compare the postoperative outcomes after totally minimally invasive right colectomy between the obese and non-obese population. Data derived from a prospectively maintained multicenter colorectal database were analysed, dividing the enrolled patients into two groups: obese (BMI &gt; 29.99) patient group and non-obese patient group. Data about gender, age, American Society of Anesthesiologists (ASA) Score, tumor characteristics, operative time, anastomosis time, extraction site, incision length, intraoperative complications, postoperative complications, postoperative recovery, specimen length and retrieved nodes were taken to assess the achievement of the oncologic standards. After a propensity score matching, a total of 184 patients was included, 92 in each group. No differences were found in terms of demographic data and tumor characteristics. Intraoperative data showed a significant difference in terms of anastomosis time in favour of non-obese group (p &lt; 0.0001). No intraoperative complications were recorded and no conversion was needed in both groups. No differences were found in terms of postoperative complications. There were no differences in terms of first mobilization (p = 0.745), time to first flatus (p = 0.241) time to tolerance to liquid and solid diet (p = 0.241 and p = 0.06) and length of hospital stay (p = 0.817). The analysis of oncologic outcomes demonstrated adequate results in both groups. The results obtained by our study confirmed the feasibility and safety of the totally minimally invasive approach even in obese population

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo &gt; 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5&nbsp;cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray’s tests p = 0.004, respectively), while recurrences were comparable (Gray’s tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI −&nbsp;4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference −&nbsp;0.3%; 1-sided 95%CI −&nbsp;5.0% to ∞). Conclusions: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

Clostridium difficile infection after stoma reversal surgery: a systematic review and meta-analysis of the literature

Background: Clostridium difficile infection (CDI) has been described in the early post-operative phase after stoma reversal. This systematic review aimed to describe the incidence of CDI after stoma reversal and to identify pre-operative variables correlated with an increased risk of infection. Methods: A systematic review of the literature was conducted according to the PRISMA guidelines in March 2024. Manuscripts were included if reported at least one patient with CDI-associated diarrhoea following stoma reversal (colostomy/ileostomy). The primary outcome of interest was the incidence of CDI; the secondary outcome was the comparison of clinical variables (age, sex, time to stoma reversal, neo-adjuvant and adjuvant therapies after index colorectal procedure) in CDI-positive versus CDI-negative patients. A meta-analysis was performed when at least three studies reported on those variables. Results: Out of 43 eligible manuscripts, 1 randomized controlled trial and 10 retrospective studies were selected, including 17,857 patients (2.1% CDI). Overall, the mean age was 64.3 ± 11.6 years in the CDI group and 61.5 ± 12.6 years in the CDI-negative group (p = 0.51), with no significant difference in sex (p = 0.34). Univariable analyses documented that the mean time to stoma reversal was 53.9 ± 19.1 weeks in CDI patients and 39.8 ± 15.0 weeks in CDI-negative patients (p = 0.40) and a correlation between neo-adjuvant and adjuvant treatments with CDI (p &lt; 0.001). A meta-analysis was performed for time to stoma reversal, age, sex, and neo-adjuvant therapies disclosing no significant differences for CDI (stoma delay, MD 11.59; 95%CI 24.32–1.13; age, MD 0.97; 95%CI 2.08–4.03; sex, OR1.11; 95%CI 0.88–1.41; neo-adjuvant, OR0.81; 95%CI 0.49–1.35). Meta-analysis including patients who underwent adjuvant therapy evidenced a higher risk of CDI (OR 2.88; 95%CI 1.01–8.17,&nbsp;p = 0.11). Conclusion: CDI occurs in approximately 2.1% of patients after stoma reversal. Although a trend of increased delay in stoma reversal and a correlation with chemotherapy were documented in CDI patients, the use of adjuvant therapy was the only possible risk factor documented on meta-analysis. PROSPERO registration number: CRD4202348470

The learning curve of TaTME for mid-low rectal cancer: a comprehensive analysis from a five-year institutional experience

Background: Transanal total mesorectal excision (TaTME) was introduced in 2009 as a dedicated approach for the treatment of mid-low rectal cancer. We aimed to describe and discuss the learning curve for 121 consecutive TaTME procedures performed by the same team. Methods: The primary outcome was the number of operations required to decrease the mean operative time (mOT). The secondary outcomes were the number of operations required to decrease the major complication (MC) rate, the anastomotic leakage (AL) rate, the clinical anastomotic failure rate, and the reoperation rate. A cumulative sum (CUSUM) curve analysis was used to identify the inflection points. As an integrative analysis, Bernoulli CUSUM curves, risk-adjusted CUSUM curves based on the observed-expected outcomes, and CUSUM curves targeting results reported in the literature were created. Results: Seventy-one cases were needed to overcome the OT learning curve sufficiently to reach mastery. The MC and reoperation rates started to decrease after the 54th case and further decreased after the 69th case. The AL rate started to decrease after the 27th case and remained stable at 5\u20135.1%. The comparison between the different phases of the learning curves confirmed these turning points. Conclusions: TaTME had a learning curve of 71 cases for the mOT, 55\u201369 cases for MCs and reoperation, and 27 cases for AL. According to our results, attention should be paid during the first part of the learning curve to avoid an increased rate of MCs and AL

The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review

Background: The gut microbiota (GM) has been proposed as one of the main determinants of colorectal surgery complications and theorized as the \u201cmissing factor\u201d that could explain still poorly understood complications. Herein, we investigate this theory and report the current evidence on the role of the GM in colorectal surgery. Methods: We first present the findings associating the role of the GM with the physiological response to surgery. Second, the change in GM composition during and after surgery and its association with colorectal surgery complications (ileus, adhesions, surgical-site infections, anastomotic leak, and diversion colitis) are reviewed. Finally, we present the findings linking GM science to the application of the enhanced recovery after surgery (ERAS) protocol, for the use of oral antibiotics with mechanical bowel preparation and for the administration of probiotics/synbiotics. Results: According to preclinical and translational evidence, the GM is capable of influencing colorectal surgery outcomes. Clinical evidence supports the application of an ERAS protocol and the preoperative administration of multistrain probiotics/synbiotics. GM manipulation with oral antibiotics with mechanical bowel preparation still has uncertain benefits in right-sided colic resection but is very promising for left-sided colic resection. Conclusions: The GM may be a determinant of colorectal surgery outcomes. There is an emerging need to implement translational research on the topic. Future clinical studies should clarify the composition of preoperative and postoperative GM and the impact of the GM on different colorectal surgery complications and should assess the validity of GM-targeted measures in effectively reducing complications for all colorectal surgery locations

Ratio-based staging systems are better than the 7th and 8th editions of the TNM in stratifying the prognosis of gastric cancer patients: A multicenter retrospective study.

BACKGROUND: The current and the previous editions of the tumor-node-metastasis (TNM) system for gastric cancer (GC; TNM8 and TNM7) have a high risk of stage-migration bias when the node count after gastrectomy is suboptimal. Hence, they are possibly not the optimal staging systems for GC patients. This study aims to compare the TNM with two systems less affected by the stage-migration bias, namely, the lymph nodes ratio (LNR) and the log odds of positive lymph nodes (LODDS), to assess which one is the best in stratifying the prognosis of GC patients. METHODS: The sample study included 1221 GC patients. Two 7-cluster staging systems based on the combination of pT categories and LNR and LODDS categories (TLNR and TLODDS) were compared with the two last editions of TNM, using the Akaike information criteria, the Bayesian information criteria, and the receiver operating characteristic (ROC) curve graphs. Further validation on an independent sample of 251 patients was carried out. RESULTS: The univariable and multivariable analyses and the ROC curves detected an advantage of the TLNR and TLODDS systems over the TNM. The TLNR and TLODDS showed the best accuracy both in the subgroup of patients with ≥16 nodes examined. The results were confirmed in the validation analysis. CONCLUSIONS: TLNR and TLODDS staging systems should be considered a valid implementation of the TNM for the prognostic stratification of GC patients. If these results are confirmed in further studies, the future implementation of the TNM should consider the introduction of the LNR or the LODDS along with the number of metastatic nodes

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections

Purpose: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. Methods: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60&nbsp;years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx\u2019s tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. Results: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p &lt; 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. Conclusion: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum