Francesco Cabras

Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer.

Background:Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer.Methods:Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored.Results:Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19%; P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13%; P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1%; hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2%; HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86).Conclusions:Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.

MUTYH-associated colon disease: adenomatous polyposis is only one of the possible phenotypes. A family report and literature review.

AIMS AND BACKGROUND The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome. PATIENTS AND METHODS A family with a history of right-sided colon cancer and multiple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MUTYH and the role of prophylactic surgery. RESULTS Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, developed four hyperplastic lesions, while the heterozygote brother had a large flat serrated adenoma of the right colon removed at the age of 50. CONCLUSION Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrated adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP.

The Role of Aspirin as Antitumoral Agent for Heavily Pretreated Patients With Metastatic Colorectal Cancer Receiving Capecitabine Monotherapy

Background The potential clinical impact of aspirin use beyond its canonical indications is a novel matter of scientific debate. In patients with metastatic colorectal cancer failing all available options, regorafenib and TAS 102 represent the only chance of treatment. Although effective, these therapeutic options bring along a not‐negligible burden in terms of economic costs and toxicity. In this setting, the indication to use aspirin in combination with chemotherapy would potentially represent a medical revolution under the economic and toxicity profile. Patients and Methods We assessed the role of aspirin in patients with metastatic colorectal cancer who failed all previous treatments and were receiving capecitabine as a salvage option before the introduction of regorafenib and TAS‐102. Results Sixty‐six patients were eligible. Twenty patients (30%) were on incidental treatment with aspirin for cardiovascular diseases. Twelve (60%) partial responses were seen in patients on treatment with aspirin, compared with 3 (6%) partial responses in the remaining patients (P = .00007). Sixteen patients on aspirin (80%) obtained disease control versus 14 (30%) patients who were not on aspirin (P = .000377). The median progression‐free survival for patients receiving treatment with aspirin was 6.5 months versus 3.3 months for patients who were not on aspirin (hazard ratio, 0.48; 95% confidence interval, 0.30‐0.79; P = .0042). A significantly improved overall survival was also evident in aspirin users (median overall survival, 14.7 vs. 8.7 months, respectively; hazard ratio, 0.43; 95% confidence interval, 0.26‐0.72; P = .0023). Conclusion Aspirin may improve the clinical outcome of heavily pre‐treated patients with metastatic colorectal cancer receiving chemotherapy. Further studies are necessary before application in the clinical practice. Micro‐Abstract The potential use of aspirin beyond recognized indications is becoming increasingly important in the oncology field of research. Besides accumulating data about aspirin in the prevention and postoperative setting for patients with colorectal cancer, we found that aspirin might have a relevant therapeutic role also in heavily pretreated patients with a potentially impressive efficacy profile, low toxicity, and negligible economic costs.

The Use of Barbed Suture for Intracorporeal Mechanical Anastomosis During a Totally Laparoscopic Right Colectomy: Is It Safe? A Retrospective Nonrandomized Comparative Multicenter Study

Background. A totally laparoscopic right colectomy could be perceived as a more challenging procedure over a laparoscopic-assisted right colectomy owing to the difficulty of intracorporeal anastomosis and the closure of the enterotomy. The aim of this study is to evaluate the safety and efficacy of the barbed auto-locking absorbable suture for the closure of an anastomotic stapler-access enterotomy during a totally laparoscopic right colectomy. Methods. From January 2010 to April 2016, data from patients who had undergone a laparoscopic right colectomy in 2 different departments of 2 institutions (the Department of General and Minimally Invasive Surgery, San Camillo Hospital in Trento and the Department of Surgical Specialties and Nephrology, University Federico II in Naples) were retrospectively analyzed. We compared the data of patients in whom the stapler-access enterotomy was closed through a conventional absorbable suture (Group A), with the data of patients in whom a stapler-access enterotomy was closed through a V-Loc 180 suture (Group B). Biometric features and intraoperative and postoperative data were collected and analyzed. Results. The 2 groups (Group A: 40 patients; Group B: 40 patients) were comparable for biometric features and postoperative outcomes. The anastomosing time was lower in Group B. A statistically significant difference was noted in the mean operative time between Groups A and B (Group A = 134.92 ± 34.17; Group B = 120.92 ± 23.27, P = .035). Only one anastomotic leakage per group was recorded, each treated with an anastomosis redo. During the reoperations, we find in both groups an intact stapler-access enterotomy. Conclusion. On retrospective analysis, barbed suture appears to be safe and efficient for closure of the stapler-access enterotomy during totally laparoscopic right colectomy.

Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor

Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non‐invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell‐free circulating DNA from CRC patients.

Single incision laparoscopic splenectomy, technical aspects and feasibility considerations

Minimally invasive techniques have been introduced to reduce morbidity related to standard laparoscopic procedures. One such approach is laparoendoscopic single-site surgery. The aim of the study was to present our initial clinical experience of using this technique for elective splenectomy. We carried out single access laparoscopic splenectomy (SALS) for an 8 cm cystic lesion of the spleen, involving the hilum, on a 38-year-old woman. The procedure was performed with a single-port device (4-channel) via a 2.5-cm umbilical incision. A flexible 5-mm optic and straight laparoscopic instruments were used. The operative time was 75 min. There was no blood loss. No complications were observed. The postoperative period was uneventful. Although substantial development of the instruments and skills is needed, this SALS technique appears to be feasible and safe. Nevertheless, further experience and observations are necessary.

Brain Volume in Early MS patients with and without IgG Oligoclonal Bands in CSF

BACKGROUND Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. AIM to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. METHODS Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. RESULTS In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. CONCLUSIONS Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.

Colon, Rectum, and Appendix

The uptake of laparoscopic colorectal surgery is increasing annually. The first laparoscopic colon resection was reported in 1991. In the United Kingdom data show that 22 % of colon resections were performed laparoscopically by 2008–2009 [1, 2].

Esophagus and Stomach

The upper gastrointestinal surgery represented one of the first applications of laparoscopy. Since the early 1990s, benign esophageal disorders like gastroesophageal reflux, achalasia, or hiatal hernia became indications for the laparoscopic approach (LA) [1, 2].

Liver, Gallbladder, and Biliary Tree

It is unclear who is the first surgeon to perform the first laparoscopic cholecystectomy (LC) [1]. However, Mouret reported, in March of 1987, a “laparoscopy, gynecological adhesiolysis, and cholecystectomy” for a 50-year-old woman [2].