Gianluca Pellino

Application of three-dimensional printing in laparoscopic dissection to facilitate D3-lymphadenectomy for right colon cancer

Complete mesocolic excision (CME) has been recently popularized in an attempt to reduce local recurrences following curative right colon cancer surgery. CME combines the concept of total mesorectal excision, which currently represents the gold standard for rectal cancer surgery, with central ligation and removal of apical nodes (D3-lymphadenectomy), routinely recommended in Japanese guidelines for T3/T4 tumours irrespective of N status and in selected T2 patients [1, 2]. Dissection of the gastrocolic trunk of Henle (GCTH) and that of the surgical trunk of Gillot (STG) are crucial steps to achieve a proper D3-lymphadenectomy. Anatomical location, vascular variability and fragility of vessels in this area increase the risk of intraoperative bleeding from the superior mesenteric vein, which might be responsible for conversion during laparoscopic surgery. Preoperative vascular imaging studies can reduce bleeding and complications in laparoscopic surgery [1]. The role of preoperative three-dimensional (3D) printing in colorectal surgery needs to be assessed. We describe the application of 3D-printing in planning laparoscopic dissection of the GCTH and STG during D3-lymphadenectomy.

Squamous Cell Carcinoma of the Anal Transitional Zone after Ileal Pouch Surgery for Ulcerative Colitis: Systematic Review and Treatment Perspectives

Background: Few cases of pouch-related cancers have been reported in ulcerative colitis (UC), and squamous cell carcinoma (SCC) is very rare. Method: A systematic review of the literature was performed to identify all unequivocal cases of pouch-related SCC in UC patients. Results: Eight cases of SCC developing after ileal pouch-anal anastomosis (IPAA) have been observed since 1978. Two arose from the pouch mucosa and 6 from below. The pooled cumulative incidence of SCC is below 0.06% after IPAA. Many patients had neoplasia on the preoperative specimen, but squamous metaplasia of the pouch or anorectal mucosa may have an important role in SCC. These patients are rarely offered chemoradiation therapy and the outcome is poor. Selected patients with SCC located close to the pouch outlet can be treated with chemoradiation prior to consideration of surgery and salvage their pouch. A chemoradiation regimen is suggested to avoid pouch excision in these patients. Conclusions: SCC is rare after pouch surgery but associated with extremely poor survival. Very low SCC can be managed with chemoradiation treatment, preserving the pouch and avoiding surgery, even in older patients. The role of pouch metaplasia, surveillance frequency, and treatment modalities after IPAA need further studying.

Metformin and Autoimmunity: A “New Deal” of an Old Drug

Metformin (dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect. Since its discovery more than 50 years ago, metformin represents a worldwide milestone in treatment of patients with type 2 diabetes (T2D). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential antiaging molecule. Moreover, emerging in vivo and in vitro evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases.

Comparison of Western and Asian Guidelines Concerning the Management of Colon Cancer

BACKGROUND: Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted. OBJECTIVE: This study aims to compare Western and Asian guidelines for the management of colon cancer. DATA SOURCES: A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network. STUDY SELECTION: Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors. MAIN OUTCOME MEASURES: The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement. RESULTS: Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US guidelines include a patient advocate in the drafting panel. LIMITATIONS: Bias may have arisen from country-specific socioeconomic and cultural issues, and from the latest available updates. CONCLUSIONS: Surgical approaches to colon cancer differ significantly among Western and Asian guidelines, reflecting different concepts of treatment. The role of adjuvant treatment in node-negative disease and quality-of-life assessment need further research.

Social media and colorectal cancer: A systematic review of available resources

Aim Social media (SM) can provide information and medical knowledge to patients. Our aim was to review the literature and web-based content on SM that is used by Colorectal Cancer (CRC) patients, as well as surgeons’ interaction with SM. Method Studies published between 2006 and 2016 were assessed. We also assessed the impact of several hashtags on Twitter with a freeware (Symplur). Results Nine studies were included assessing Twitter (78%), Forums/Cancer-survivor networks (33%), and Facebook (22%). Aims included use of SM by CRC patients (67%), cancer-specific usage of SM with different types of cancer (44%), content credibility (33%), and influence in CRC awareness (33%). Prevention was the most common information that CRC patients looked for, followed by treatment side-effects. Only 2% of CRC SM users are doctors. SM use by colorectal consultants was suboptimal. Only 38% of surgeons had a LinkedIn account (most with less than 50 connections), and 3% used Twitter. A steep increase of tweets was observed for searched Hashtags over time, which was more marked for #ColonCancer (+67%vs+38%, #Coloncancer vs #RectalCancer). Participants engaged with colon cancer increased by 85%, whereas rectal cancer ones increased by 29%. The hashtag ‘#RectalCancer’ was mostly tweeted by colorectal surgeons. The official twitter account of American Society of Colorectal Surgeons (@fascrs_updates) was the most active account. Conclusion CRC patients and relatives are increasingly engaging with SM. CRC surgeons’ participation is poor, but we confirm a trend toward a greater involvement. Most SM lack of authoritative validation and the quality of shared content still is largely anecdotic and not scientifically evidenced-based. However, SM may offer several advantages over conventional information sharing sources for CRC patients and surgeons, and create connections with mutual enrichment.

A Review of the Role of Neurotensin and Its Receptors in Colorectal Cancer

Neurotensin (NTS) is a physiologically occurring hormone which affects the function of the gastrointestinal (GI) tract. In recent years, NTS, acting through its cellular receptors (NTSR), has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC), a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC. Furthermore, blockade and modulation of the NTS/NTSR signalling pathways appears to reduce CRC growth in cell cultures and animal studies. Lastly, NTS/NTSR also shows potential of being utilised as a diagnostic biomarker for cancers as well as targets for functional imaging. We summarise the existing evidence and understanding of the role of NTS and its receptors in CRC.

Colorectal cancer diagnosed during pregnancy: systematic review and treatment pathways.

The aim of this study was to identify the mode of presentation and incidence of colorectal cancer in pregnancy (CRC-p), assess the outcomes of the mother and foetus according to gestational age, treatment delivered and cancer features and location. A systematic review of the literature was carried out to identify studies reporting on CRC-p and pooled analysis of the reported data. Seventy-nine papers reporting on 119 patients with unequivocal CRC-p were included. The calculated pooled risk is 0.002% and age at diagnosis has decreased over time. The median age at diagnosis was 32 (range, 17–46) years. Twelve per cent, 41 and 47% of CRC-p were diagnosed during the first, second and third trimester. The CRC-p site was the colon in 53.4% of cases, the rectum in 44% and multiple sites in 2.6%. Bleeding occurred in 47% of patients, abdominal pain in 37.6%, constipation in 14.1%, obstruction in 9.4% and perforation in 2.4%. Out of 82 patients whose treatment was described, 9.8% received chemotherapy during pregnancy. None of their newborns developed permanent disability, one developed hypothyroidism and 72% of newborns were alive. Vaginal delivery was possible in 60% of cases. Anterior resection was performed in 30% of patients and abdominoperineal excision of the rectum in 14.9%. Five patients had either synchronous (60%) or metachronous liver resection (40%). The median survival in these patients was 42 (0–120) months. Fifty-five per cent of patients were alive at the last available follow-up. The median survival of the mother was 36 (0–360) months. Patients with rectal cancer had longer survival compared with patients with colon cancer (P=0.0072). CRC-p is rare, leading to symptoms being overlooked, and diagnosis made at advanced stages. Cases described in the literature include patients who had cancer before pregnancy or developed it after delivery. Survival has not increased over time and the management of these patients requires collaboration between specialties and active interaction with the patients.

Immunosuppression may exert a hypoxia-mediated carcinogenetic effect in long-standing fistulizing Crohn’s disease

References 1 Wardle RA, Mayberry JF. Patient knowledge in inflammatory bowel disease: the Crohn’s and Colitis Knowledge Score. Eur J Gastroenterol Hepatol 2014; 26:1–5. 2 Eaden JA, Abrams K, Mayberry JF. The Crohn’s and Colitis Knowledge Score: a test for measuring patient knowledge in inflammatory bowel disease. Am J Gastroenterol 1999; 94:3560–3566. 3 Butcher RO, Law TL, Prudham RC, Limdi JK. Patient knowledge in inflammatory bowel disease: CCKNOW, how much do they know? Inflamm Bowel Dis 2011; 17:E131–E132. 4 Selinger CP, Lal S, Eaden J, Jones DB, Katelaris P, Chapman G, et al. Better disease specific patient knowledge is associated with greater anxiety in inflammatory bowel disease. J Crohns Colitis 2013; 7:e214–e218. 5 Limdi JK, Butcher RO. Information resources and inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:E89–E90.

The effect of adjuvant chemotherapy on survival and recurrence after curative rectal cancer surgery in patients who are histologically node negative after neoadjuvant chemoradiotherapy

The aim of this study was to evaluate whether adjuvant chemotherapy will affect recurrence rate or disease‐free and overall survival in patients with rectal adenocarcinoma who were staged with MRI node‐positive disease (mrN+) preoperatively. These patients underwent neoadjuvant chemoradiotherapy with curative rectal cancer surgery and their pathological staging was negative for nodal disease (ypN0). There is no consensus on the role of adjuvant chemotherapy in such patients.

Preoperative surgical planning based on cadaver simulation and 3D imaging for a retrorectal tumour: description and video demonstration

Retrorectal or presacral tumours include rare lesions growing into the retrorectal space. A recent systematic review with 82 patients found that these tumours are more frequent in women, mostly occurring around 40 years of age. In up to 95% of reported cases the mass was benign, schwannoma accounting for 33% of them [1]. Indications for surgery include compression of surrounding structures, symptoms, and features suspicious of malignancy or malignant transformation. According to tumour and patient features, different surgical approaches have been proposed. Minimally invasive surgery can be safely performed [1, 2], but no criteria have been agreed upon for selecting patients suitable for such an approach. It has been reported that there are no differences in the median size of the tumours between those removed by open vs minimally invasive surgery. However, solid or very large masses and a narrow pelvis could preclude minimally invasive approaches [1]. We describe our approach to retrorectal tumours, based on three-dimensional (3D) imaging reconstruction combined with preoperative strategy planning with a cadaver simulation.