Canonical and uncanonical pathogenic germline variants in colorectal cancer patients by next-generation sequencing in a European referral center.

BACKGROUND: Despite increasing use of next-generation sequencing (NGS), data concerning the gain in germline pathogenic variants (PVs) remain scanty, especially with respect to uncanonical ones. We aimed to verify the impact of different cancer predisposition genes (CPGs) on colorectal cancer (CRC) in patients referred for genetic evaluation. MATERIALS AND METHODS: We enrolled for NGS, by Illumina TruSight Cancer panel comprising 94 CPGs, 190 consecutive subjects referred for microsatellite instability (MSI) CRC, polyposis, and/or family history. RESULTS: Overall, 51 (26.8%) subjects carried 64 PVs; PVs coexisted in 4 (7.8%) carriers. PVs in mismatch repair (MMR) genes accounted for one-third of variant burden (31.3%). Four Lynch syndrome patients (20%) harbored additional PVs (HOXB13, CHEK2, BRCA1, NF1 plus BRIP1); such multiple PVs occurred only in subjects with PVs in mismatch syndrome genes (4/20 versus 0/31; P = 0.02). Five of 22 (22.7%) patients with MSI cancers but wild-type MMR genes harbored PVs in unconventional genes (FANCL, FANCA, ATM, PTCH1, BAP1). In 10/63 patients (15.9%) with microsatellite stable CRC, 6 had MUTYH PVs (2 being homozygous) and 4 exhibited uncanonical PVs (BRCA2, BRIP1, MC1R, ATM). In polyposis, we detected PVs in 13 (25.5%) cases: 5 (9.8%) in APC, 6 (11.8%) with biallelic PVs in MUTYH, and 2 (3.9%) in uncanonical genes (FANCM, XPC). In subjects tested for family history only, we detected two carriers (18.2%) with PVs (ATM, MUTYH). CONCLUSION: Uncanonical variants may account for up to one-third of PVs, underlining the urgent need of consensus on clinical advice for incidental findings in cancer-predisposing genes not related to patient phenotype.

Prognostic role of immunohistochemical overexpression of the p16 protein in women under the age of 35 and diagnosed with HSIL (CIN2) subjected to "cervix sparing" excision.

OBJECTIVE: To evaluate the role of immunohistochemical staining overexpression of p16 protein (p16 IHC) as a prognostic factor of persistence or recurrence of intraepithelial disease after excision procedure in young women diagnosed with HSIL (CIN2). PATIENTS AND METHODS: 62 women with a histological diagnosis of HSIL (CIN2) subjected to "cervix sparing" excisional procedure were included in this retrospective study. All had age less than or equal to 35 years, negative history of immunosuppression, available follow-up, and assessment of the resection margins state. Immunohistochemical staining for the p16 protein was evaluated on reviewed and confirmed HSIL (CIN2) histological specimens with negative resection margins. The post-treatment follow-up, including cytology, colposcopy, and histology, ranged from a minimum of 6 months to a maximum of 60 months. The persistence or recurrence of SIL during the follow-up period was based on histologic referral and defined as "the presence of SIL", "the presence of HSIL" and "progression to HSIL (CIN3)". RESULTS: 31/62 patients were positive for immunostaining (p16 IHC+), and 31/62 were negative (p16 IHC-). Persistence or recurrence after excision occurred more frequently within the p16 IHC+ than in p16 IHC- group, both as SIL (29% p16 IHC- vs. 32.3% p16 IHC+, p = 0.783) and HSIL (6.5% p16 IHC- vs. 12.9% p16 IHC+, p = 0.671). None of the patients in the p16 IHC- group showed progression to CIN3 for the entire observation period, whereas 9.7% of p16 IHC+ women progressed to CIN3 lesion (p = 0.042). The p16 IHC positivity showed a significant association with progression to CIN3 in 5 years of follow-up (p = 0.029) and with the presence of SIL after two years of follow-up (p = 0.031). The differences between the two groups increased after two years post-treatment: the p16 IHC- patients still had SIL only in 3.2% of cases and no longer had HSIL, while the p16 IHC+ women still showed SIL in 19.4% and HSIL in 6.5% of cases. The negative predictive value (NPV) of p16 IHC in predicting SIL's presence after treatment increased with the severity of the lesion (NPV for SIL 70.97%, for HSIL 93.55%, for CIN3 100%). CONCLUSIONS: The study suggests that young patients with p16 IHC- HSIL (CIN2) have a better post-excisional course of the cervical intraepithelial disease compared to p16 IHC+ women and that p16 IHC could have prognostic utility during the long-term follow-up, especially in forecasting progression to CIN3 in consideration of the high NPV (up to 100%). The efficacy of the adjuvant HPV vaccination in the management of HSIL (CIN2) p16+ young women is to be evaluated as part of the fertility-sparing treatment.

Full robotic Hartmann's reversal: technical aspects and preliminary experience.

AIM: Laparoscopic Hartmann's reversal (HR) is a major abdominal operation that is associated with considerable morbidity and mortality. The robotic approach, with its intrinsic advantages, could potentially overcome the technical complexity of laparoscopy. The aim of this study was to evaluate the short-term results of a series of 24 robotic HR cases. METHOD: The data from 24 patients who underwent robotic HR between September 2016 and July 2019 at two different institutions were prospectively collected and retrospectively analysed. A full robotic single-docking reversal procedure with intracorporeal anastomosis was performed in all patients. RESULTS: The mean age and body mass index of the patients were 69 years and 26 kg/m2 , respectively. Of the patients, 58% were ≥ 70 years old and 42% had comorbidities (mean Charlson Comorbidity Index 3). The mean operating time was 240 min. There were no cases of conversion to the open or laparoscopic approach. No diverting loop ileostomies were constructed. The mean length of hospital stay was 6 days. Minor complications were recorded in three patients. Neither major complications nor 30-day readmissions were registered. CONCLUSIONS: Robotic HR is a feasible and safe procedure. The robotic approach has low rates of major complications and conversion and could potentially increase the number of patients undergoing HR.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

Fashioning enterotomy closure after totally laparoscopic ileocolic anastomosis for right colon cancer: a multicenter experience.

BACKGROUND: Laparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis. METHOD: A multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures' materials, interrupted versus running suture and the presence of deep corner suture has been investigated. RESULTS: We collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis. CONCLUSIONS: Fashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.

Sensitivity and specificity values of high-risk HPV DNA, p16/ki-67 and HPV mRNA in young women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL).

OBJECTIVE: The aim of the study was to evaluate the sensitivity and specificity values of high-risk HPV DNA test, p16/ki-67, and HPV mRNA in histologically high-grade cervical intraepithelial lesions (CIN2-CIN3) in women aged 21-24 years with diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) at pap smear. PATIENTS AND METHODS: 342 patients between 21-24 years old, attending spontaneously our clinics, 118 with ASCUS and 224 with LSIL, were enrolled in the study. All patients underwent colposcopy and biopsies were performed in the areas with major changes. All patients were tested at the same time for p16/ki-67, high-risk HPV DNA and HPV mRNA. RESULTS: Nineteen out of 118 women with ASCUS showed a high-grade cervical intraepithelial lesion, 11 out of 118 (9.32%) CIN2, and 8 out of 118 (6.78%) CIN3. The sensitivity of high-risk HPV DNA was 99.9%, and the specificity 23.2%; p16/ki-67 pointed out a sensitivity of 90.9%, and a specificity of 81.8%; HPV mRNA showed a sensitivity of 81.8%, and specificity of 87.9% in CIN2 lesions. In CIN3 lesions, the sensitivity of high-risk HPV DNA was 99.9%, while the specificity was 19.1%; p16/ki-67 showed a sensitivity of 99.9%, and a specificity of 73.7%; HPV mRNA relived a sensitivity of 87.5%, and a specificity of 80.8%. In women with LSIL, a total of 42/224 (18.75%) of CIN2 were found at the histopathological examination, while 17/224 (7.59%) women presented a CIN3. No case of invasive cancer was identified. High-risk HPV DNA was positive in 190/224 (84.8%), p16/ki-67 in 119/224 (53.1%), and HPV mRNA in 104/224 (46.4%). In women with CIN2, the sensitivity of high-risk HPV DNA was of 92.8%, and the specificity 17.5%, the sensitivity of p16/ki-67 was 95.2%, and specificity 61.8%. HPV mRNA showed a sensitivity of 88.8% and a specificity of 87.8%. In women with CIN3, the sensitivity of high-risk HPV DNA was 88.2%, and the specificity 29.7%; p16/ki-67 pointed out a sensitivity of 94.1%, and a specificity of 49%; HPV mRNA showed a sensitivity of 88.2% and a specificity of 80.6. CONCLUSIONS: Taking into account the high rate of spontaneous regression of high-grade lesions in young women, these tests, in particular, the HPV mRNA test, used as a triage test for ASCUS or LSIL, can modify follow-up triage strategy. In fact, this biomarker, due to its high specificity, could lead to a cytology repetition instead of an immediate colposcopy, avoiding over diagnosis and potential overtreatment in this category of women.

Strategies for delivery of faecal occult blood test kits and participation to colorectal cancer screening in the Emilia-Romagna Region of Italy.

There is a lack of agreement about which routine invitation strategy should be adopted in colorectal cancer screening. We conducted an observational study to assess the impact of three invitation strategies on participation. Invitation records for the years 2005-2009 were evaluated. There were 2,234,276 invitations from 1,230,683 individuals. Among first invitations, participation associated with direct mailing of the faecal occult blood test kits was slightly lower (relative risk, RR 0.985; 95% confidence interval 0.979-0.990) than that of the reference invitation strategy, that is, the distribution of the test kits by pharmacies. In repeated invitations/previous non-responders, the participation associated with the direct mailing of the test kits was even lower (RR 0.914; 95% confidence interval 0.895-0.933) and this was also the case for the distribution of the test kits by primary care centres (RR 0.983; 95% confidence interval 0.971-0.995). In contrast, in repeated invitations/previous responders, the impact of primary care centres and direct mailing of the test kits was greater than the use of pharmacies, showing only modest RRs: 1.021 (95% confidence interval 1.019-1.023) and 1.029 (95% confidence interval 1.025-1.033) respectively. The faecal occult blood test mailing strategy modestly increased participation in previous responders.

Suprapubic approach for robotic complete mesocolic excision in right colectomy: Oncologic safety and short-term outcomes of an original technique.

INTRODUCTION: Right-sided colon cancer has a worse prognosis than left-sided colon cancer. Complete mesocolic excision (CME) with central vessels ligation (CVL) reduces local recurrence, but is technically demanding, particularly with a laparoscopic approach. Aim of this study is to describe a new robotic approach to right colectomy with CME and CVL and to report oncologic safety and short term outcomes. METHODS: Twenty consecutive patients were included. All patients had a right colon adenocarcinoma and underwent right colectomy with a suprapubic approach. Surgery was realized with the Da Vinci Xi® system and all trocars were placed along a horizontal line 3-6 cm above the pubis. CME with CVL was realized in all the patients. Data analysed were: duration of surgery, conversions to open surgery, intraoperative and postoperative complication by Clavien Dindo classification, margins of resections, length of specimen and number of lymph nodes retrieved. RESULTS: Patients median age was 69 years, median body mass index was 27 kg/m2. Median operative time was 249 min, blood loss was negligible, no conversions to open or laparoscopic surgery occurred. Median hospital stay was six days; two postoperative grade IIIa Clavien-Dindo complications occurred, no 30-days postoperative death was registered. Resection margins were negative in all patients; median tumour diameter was 3.6 cm, median specimen length was 40 cm, median number of harvested lymph nodes was 40. CONCLUSIONS: Robotic right colectomy with CME using a suprapubic approach is a feasible and safe technique that allows for an extended lymphadenectomy and provides high quality surgical specimens.

Cervical carcinogenesis, bacterial vaginosis, HPV-mRNA test and relapse of CIN2+ after loop electrosurgical excision procedure (LEEP).

OBJECTIVE: The aim of the study was to evaluate the relationship between bacterial vaginosis (BV) and relapse of cervical intraepithelial neoplasia grade 2 or more (CIN2+) after Loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: One hundred four patients who underwent LEEP for CIN2+ were followed up every six months for three years. Fifty-three were negative for BV and fifty-one were positive. Each clinical control included Pap test, colposcopy, Amsel criteria test, HPV-DNA, and HPV-mRNA test. RESULTS: Patients' age, presence of BV, positivity to HPV-DNA and HPV-mRNA tests were analyzed. The average age of patients was 42.5 ± 8.92 years (median: 42.5; range from 27 to 58 years). The minimum follow-up was 6 months and maximum 36 months (average: 22.8 ± 4.53; median: 24). The 10% of the patients with HPV-mRNA test negative had relapsed, compared to 45% of patients with HPV-mRNA test positive. Among the 53 patients without BV the 20% had relapsed compared with 23% of 51 patients with diagnosis of BV. CONCLUSIONS: There is no evidence for higher percentage of relapse in patients with BV, submitted to excisional procedure for CIN2+ associated to HPV-m-RNA test positivity. There is only a correlation among BV and relapse of CIN2+ lesions after LEEP.

Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial.

BACKGROUND: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. METHODS: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. RESULTS: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. CONCLUSIONS: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov , NCT02738190.

Identification of ageing biomarkers in human dermis biopsies by thermal analysis (DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR).

BACKGROUND/PURPOSE: The purpose of this clinical study was to identify suitable biomarkers for a better understanding of the molecular and organizational changes in human dermis during intrinsic and extrinsic ageing. METHODS: Sun-exposed and non-exposed skin biopsies were collected from twenty-eight women devised in two groups (20-30 and ≥60 years old). The hydric organization and thermal transitions were determined by Differential Scanning Calorimetry (DSC). Fourier Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis and to quantify the different absorbance ratio. RESULTS: The amounts of total, freezable and unfreezable water were determined. A significant increasing amount of freezable water is evidenced in sun-exposed area skin of aged group compared with young group (P=.0126). Another significant effect of extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the main protein component of dermis. The only significant effect of intrinsic ageing (P=.0184) is an increase of the heat-stable fraction of collagens in dermis. CONCLUSION: DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with a high reproducibility. The combination of these techniques is useful for a better understanding of human skin modifications with intrinsic and extrinsic ageing.

Expression of E6/E7 HPV-DNA, HPV-mRNA and colposcopic features in management of CIN2/3 during pregnancy.

OBJECTIVE: The incidence of abnormal cervical cytology in pregnancy is similar to that reported for non-pregnant women. Furthermore, 1% of pregnant women annually screened for cervical cancer will be diagnosed with cervical intraepithelial neoplasia (CIN) of various degrees. For this reason, Pap smear should be performed in the first trimester of pregnancy. The persistence of HR-HPV infection is related to the development of CIN. However, the relationship between CIN and HR-HPV infection during pregnancy and postpartum can hardly be found. The aim of this work was to assess the proper management of abnormal cytology during and after pregnancy evaluating regression rate, persistence rate and risk of progression and the predictive role of HPV molecular tests. PATIENTS AND METHODS: Patients with abnormal cervical cytology were followed-up using colposcopy and colposcopy-directed biopsies every 12 weeks. Molecular tests were performed at the moment of the cytological diagnosis. Patients not treated in pregnancy were re-evaluated with cytology, colposcopy, biopsies, HPV-DNA test and HPV-mRNA test for a final diagnosis 8 weeks postpartum. Women with a persistent CIN 2-3 lesion at this follow-up check, underwent an excisional procedure by LEEP and then re-evaluated every 6 months for a year. RESULTS: HPV-DNA test showed a sensitivity of 90.5% and a negative predictive value of 96.4%. Specificity and positive predictive values were 67.9% and 43.2%, respectively. For HPV-mRNA test, a sensitivity of 76.2% and a NPV of 93.9% were found; specificity and PPV were 98.7% and 94.1% respectively. CONCLUSIONS: An observational management based on the use of molecular test and particularly HPV-mRNA test for its higher specificity, is a reasonable possibility in the follow-up of CIN2/3 lesions during pregnancy.

Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

OBJECTIVE: The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. PATIENTS AND METHODS: Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. RESULTS: Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. CONCLUSIONS: None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

Quality of sex life in endometriosis patients with deep dyspareunia before and after laparoscopic treatment.

PURPOSE: The present work aims at showing how dyspareunia linked to endometriosis can affect the life of fertile age women and how surgical treatment of endometriosis can relieve painful symptoms and consequently improve sex and social life. METHODS: From a cohort of 320 women with a clinical and instrumental diagnosis of pelvic endometriosis, 67 patients were selected. These patients had deep dyspareunia that underwent laparoscopic surgical treatment. All the patients had filled out a pre- and post-surgery questionnaire. RESULTS: Six months after laparoscopic treatment, a significant reduction of dyspareunia was recorded, per VAS scores. A statistically significant improvement in sex life was observed between the pre- and post-surgical condition: in particular, an increased number of coituses and of non-difficult coituses, a higher number of patients who declared that pain did not negatively affect sexual pleasure and of patients achieving orgasm. CONCLUSIONS: The quality of the sex life in patients with endometriosis and dyspareunia showed significant improvement 6 months after laparoscopic treatment. In view of the diagnostic delay characterizing this disease and confirmed by our results, it is essential to involve a multidisciplinary team to assess all the signs and symptoms of endometriosis that may appear in a women of fertile age. This clinical approach is able to ensure a treatment that is as personalized as possible and an appropriate follow-up also with the objective of preserving reproductive performance.

Feasibility of office CO2 laser surgery in patients affected by benign pathologies and congenital malformations of female lower genital tract.

OBJECTIVE: Traditional surgery presents some disadvantages, such as the necessity for general anesthesia, hemorrhage, recurrence of pathology, and the possible onset of dyspareunia due to an excessive scarring. CO2 laser surgery might resolve these problems and might be employed in a wider range of clinical indications than usual. We examined the results of CO2 laser surgery in patients affected by benign pathologies and congenital malformations of the female lower genital tract. PATIENTS AND METHODS: In this observational study, we enrolled 49 women who underwent CO2 laser surgery for the following indications: Bartholin's gland cyst, imperforate hymen, vaginal septum, Nabothian cyst, and vaginal polyps. Feasibility, cost-effectiveness, complication rate, recurrence rate, short- and long-term outcomes were assessed. RESULTS: All procedures were carried out in a short operative time, without any intraoperative complications. Only 1 (2.0%) out of 49 patients required a hemostatic suture for bleeding. Postoperative period was uneventful in all patients, except 6 (12.2%) out of 49 patients who reported pain one day after surgery, successfully treated with paracetamol. Healing was rapid and excellent in all cases; no wound infection, scarring or stenosis were noticed. Preoperative symptoms reduced or disappeared in all cases. No recurrence was observed and no re-intervention was needed. CONCLUSIONS: CO2 laser surgery provides several advantages over traditional surgery, as its systematic use in treating pre-invasive, benign, and congenital pathologies of the female lower genital tract reduces patient discomfort, improves short- and long-term outcomes, and optimizes cost-effectiveness.

Challenges with robotic low anterior resection.

Dramatic improvements in the local recurrence rate of patients with rectal cancer have been observed after the introduction of the embriologically-based concept of total mesorectal excision by Heald more than 30 years ago. During the last decades, advances in multimodal treatment have further contributed to improve outcomes, but surgery still play a major role. Laparoscopic surgery for rectal cancer has been validated in randomized controlled trials to be oncologically as safe and effective as the open approach with better short-term postoperative outcomes. Nevertheless, laparoscopic low anterior resection continues to be challenging because of technical constraints and a steep learning curve. Robotic surgery may potentially offer significant advantages in rectal cancer surgery thanks to its technological features. This paper summarizes the current available evidence and highlights the most challenging aspects of robotic low anterior resection, with supporting data from the literature and from the authors' nearly ten-year experience in the field.