Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

The adipose tissue and the involvement of the renin-angiotensin-aldosterone system in cardiometabolic syndrome.

Cardiometabolic diseases are linked to a cluster of modifiable factors, including risk factors closely related to central adiposity. Chronic renin-angiotensin-aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to this clinical condition. RAAS components are locally expressed in the vessels and adipose tissue. This review appoints RAAS, through the classical and the alternative view, as the main mediator of the cross-talk in cardiometabolic syndrome.

Bottom-up engineering of the surface roughness of nanostructured cubic zirconia to control cell adhesion.

Nanostructured cubic zirconia is a strategic material for biomedical applications since it combines superior structural and optical properties with a nanoscale morphology able to control cell adhesion and proliferation. We produced nanostructured cubic zirconia thin films at room temperature by supersonic cluster beam deposition of nanoparticles produced in the gas phase. Precise control of film roughness at the nanoscale is obtained by operating in a ballistic deposition regime. This allows one to study the influence of nanoroughness on cell adhesion, while keeping the surface chemistry constant. We evaluated cell adhesion on nanostructured zirconia with an osteoblast-like cell line using confocal laser scanning microscopy for detailed morphological and cytoskeleton studies. We demonstrated that the organization of cytoskeleton and focal adhesion formation can be controlled by varying the evolution of surface nanoroughness.

Sweat analysis with a wearable sensing platform based on laser-induced graphene.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line.

Non-ohmic behavior and resistive switching of Au cluster-assembled films beyond the percolation threshold.

Networks based on nanoscale resistive switching junctions are considered promising for the fabrication of neuromorphic computing architectures. To date random networks of nanowires, nanoparticles, and metal clusters embedded in a polymeric matrix or passivated by shell of ligands or oxide layers have been used to produce resistive switching systems. The strategies applied to tailor resistive switching behavior are currently based on the careful control of the volume fraction of the nanoscale conducting phase that must be fixed close to the electrical percolation threshold. Here, by blending laboratory and computer experiments, we demonstrate that metallic nanostructured Au films fabricated by bare gold nanoparticles produced in the gas phase and with thickness well beyond the electrical percolation threshold, show a non-ohmic electrical behavior and complex and reproducible resistive switching. We observe that the nanogranular structure of the Au films does not evolve with thickness: this introduces a huge number of defects and junctions affecting the electrical transport and causing a dynamic evolution of the nanoscale electrical contacts under the current flow. To uncover the origin of the resistive switching behavior in Au cluster-assembled films, we developed a simple computational model for determining the evolution of a model granular film under bias conditions. The model exploits the information provided by experimental investigation about the nanoscale granular morphology of real films. Our results show that metallic nanogranular materials have functional properties radically different from their bulk counterparts, in particular nanostructured Au films can be fabricated by assembling bare gold clusters which retain their individuality to produce an all-metal resistive switching system.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Nanostructured Graphene Surfaces Promote Different Stages of Bone Cell Differentiation.

Nanostructured graphene films were used as platforms for the differentiation of Saos-2 cells into bone-like cells. The films were grown using the plasma-enhanced chemical vapor deposition method, which allowed the production of both vertically and horizontally aligned carbon nanowalls (CNWs). Modifications of the technique allowed control of the density of the CNWs and their orientation after the transfer process. The influence of two different topographies on cell attachment, proliferation, and differentiation was investigated. First, the transferred graphene surfaces were shown to be noncytotoxic and were able to support cell adhesion and growth for over 7 days. Second, early cell differentiation (identified by cellular alkaline phosphatase release) was found to be enhanced on the horizontally aligned CNW surfaces, whereas mineralization (identified by cellular calcium production), a later stage of bone cell differentiation, was stimulated by the presence of the vertical CNWs on the surfaces. These results show that the graphene coatings, grown using the presented method, are biocompatible. And their topographies have an impact on cell behavior, which can be useful in tissue engineering applications.

Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis.

Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts considered premalignant lesions in the large bowel. Genomic instability at short tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI. Ten patients were members of HNPCC families; 7 patients had no family history of cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from patients with HNPCC. MSI was not related to histology and size of ACF. A progressive increase in instability as estimated by the number of shifted bands was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all MSI-positive lesions in patients with HNPCC. These observations provide evidence of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early event both in HNPCC and in sporadic colorectal carcinogenesis, although in the latter it seems infrequent.

Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study.

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P =.002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

Primary adenocarcinoma of the angle of Treitz. Case report and review of the literature.

We describe a 54-year-old man who was referred with the diagnosis of adenocarcinoma of the angle of Treitz and treated with the use of a duodenojejunal segmentary resection. After a review of the literature, we emphasize the difficulty of making an early diagnosis and discuss the most appropriate surgical treatment of tumors of the angle of Treitz. The better prognosis of these neoplasms compared with those of the proximal duodenum can be supported by some embryological findings observed from a different research project currently in progress.

Embryologic bases of extended radical resection in pancreatic cancer.

OBJECTIVE: To analyze whether an embryologic "rationale" exists to the clinical and anatomicopathological data that suggest the execution of extended resections in patients with pancreatic cancer. METHODS: Reconstruction of serial histological sections of 18 human embryos and fetuses regarding the pancreatic region; anatomical microdissections of two 9-month fetuses. RESULTS: The ventral and dorsal pancreatic buds can be identified until the eighth week of development. A close developmental relationship between the dorsal pancreas and the lymphatic and nervous structures in the dorsal mesogastrium is observed. Other lymphatic stations are exclusively related to the ventral pancreas. The posterior fusion of the dorsal mesogastrium is a late event in embryologic development. CONCLUSIONS: The complete fusion of the 2 pancreatic buds occurs later than previously reported in the literature. The close embryologic relations of these buds with the lymphatic and nervous peripancreatic structures may support the need for extended resections in patients with pancreatic cancer.

Questions about the uncertain presence of muscle spindles in the human external anal sphincter.

The verification of the uncertain presence of muscle spindles in the external anal sphincter is important in the comprehension of the pathophysiology of continence. The authors failed to demonstrate these proprioceptive structures in 10 human sphincters examined with different histological techniques, whereas they found some typical muscle spindles in the puborectalis muscles. The possible interpretations of the different results on the subject in the literature together with their functional implications are discussed.

Ileo-colon-rectoplasty. An experimental morpho-functional study on the pig.

A small bowel loop was interposed, isoperistaltically or pouch-shaped between colon and rectum, (ileo-colon-rectoplasty) in 8 pigs to clarify whether the small intestine can push the semi-solid and septic content of the colon, and whether the function and morphology of the loop are modified with respect to the original. A radiographic and histologic study was performed 6 months after the operation. The structural modifications of the interposed small bowel consist of disappearance of folds, villous atrophy, superficial appearance of the glandular crypts, and, only in the isoperistaltic loop, hypertrophy of the muscular layers. Any modification in the morphologic aspect of the pouch has not been observed, as shown by the radiographic barium enema. Therefore the mucosa of the grafted ileum suffered an architectural change caused from the contact with the fecal material. The lack of structural modifications of the muscular layers and the dimensions of the above colon of the interposed ileal pouch represents an indirect proof of the correct function of reservoir ejection. The experimental results obtained confirm the applicability of this technique in the reconstruction of transit after wide resection of the left colon and rectum, for technical reasons, in man.

Postnatal development of intestinal villi in the rat. Determination of villus size gradient.

The existence of the so called "Villus Size Gradient" (VSG) which defines the proportional decrease in height of intestinal villi from duodenum to ileum is well documented in adult animals and man. The aim of this study is to define whether the VSG is present since birth or, if not, when and why it appears. We have measured the height of intestinal villi in 25 rats: 5 at 1 day from birth, 5 at 5 days, 5 at 8 days, 5 at 15 days and 5 at 30 days. We have prepared histological slides of a duodenal, jejunal and ileal tract of each animal and measured the height of villi on microphotographs. At day 1 we observed a higher size of duodenal villi statistically significant with respect to jejunum and ileum, while at day 5 no differences were observed between the various intestinal tracts. The VSG become evident 8 days after birth progressively increasing to day 30. The predominance of duodenum present at birth is therefore probably due to the fetal developmental growth which is known to be more precocious in duodenum than in more distal tracts. Five days after birth the intestinal villi are equally developed, while in later ages the VSG appears. So we can conclude that the VSG is a consequence of luminal and humoral factors and not a predetermined event.

The development of the suprarenal gland: surgical and anatomical considerations.

BACKGROUND: Aim of this research is to study the situation and relationships of the adrenal gland in the first stage of development in order to give some contributes for the application of laparoscopic adrenalectomy; in the meantime we describe the series of the debate changes occurring in the constitution of the cortex and medulla. METHODS: Analysis of histologic slices of thoraco-abdominal and abdominal regions of human embryos and fetuses ranging from the fifth (12 mm CR) to the twentieth week (170 mm CR). RESULTS: At 12 mm CR an unique type of cells is present in the cortex; at 16 mm CR there are two different groups of cells. Sympathogonia enter into the cortex at 16 mm CR. The right adrenal gland seems enclosed into the liver and a ligament containing the middle adrenal vein reaches the vena cava inferior sulcus. The left adrenal gland, through the coelomic cavity, is in relationship with the stomach, the medial border of the spleen and the pancreatic body contained in the primitive dorsal mesogastrium. CONCLUSIONS: The timing of penetration of the ganglion cells into the cortex is defined as well as the hypothesis that the matrix of the fetal and definitive cortex is the same: moreover the study of the early development allows to understand the main characteristics of both the adrenal glands which are significant for a rational and differential laparoscopic approach.

[The surgical approach to adrenal incidentaloma]. / L'approccio chirurgico all'incidentaloma surrenalico.

In this paper the Authors analyse the indications for treatment of adrenal incidentaloma by making a retrospective review of this series. These indications are compared with recent trends which have emerged in the literature.

Observations on surgical anatomy for rectal cancer surgery.

BACKGROUND/AIMS: The investigators studied the surgical anatomy of the main structures involved in the mobilization of the rectum (Denonvilliers' fascia, mesorectum, middle rectal artery, superior and inferior hypogastric plexuses). METHODOLOGY: The study was carried out on 20 cadavers (17 unembalmed and 3 embalmed). To study Denonvilliers' fascia, ten embryos and fetuses (11 mm to 80 mm CRL) were also examined. RESULTS: Denonvilliers' fascia originates from the fusion of the primary pouch of Douglas. The two leaves making up this structure are easily separated. The mesorectum surrounds the rectum on three sides; it is easily separated from the presacral fascia and its connective tissue is bordered by a thin membrane. The middle rectal artery varies in appearance rate, origin, size, distribution and anastomosis. It runs under the lateral ligament and also sends branches to the genital apparatus. Of the two hypogastric plexuses, the inferior is the most difficult one to identify. Its superior branches extend to the rectum, and the inferior ones to the genital apparatus. Because the anterior part contains the parasympathetic nerves and the middle rectal artery, this region is at major risk during surgical dissection. CONCLUSIONS: A sound understanding of the surgical anatomy of the rectum enables the surgeon to perform a more correct and reasonable procedure in terms of both the extent of surgical treatment and the preservation of important anatomical structures.

[Suspensory elements of the anal canal. Anatomo-surgical considerations]. / Elementi di sospensione del canale anale. Considerazioni anatomo-chirurgiche.

Continence depends not only on correct muscular function but also on the integrity of the suspensory structures of the anal canal, the latter being the subject of this study performed on embryological and adult specimens. The role of the perineal body as an insertion tendon common to all the striated muscles (pubo-coc-cygeus, superficial striated sphincter) which anchor the anal canal to the surrounding structures is pointed out. The characteristic behaviour of the longitudinal muscle that links the striated musculature to the visceral cylinder is also described.