Multiple aspects of matrix stiffness in cancer progression.

The biophysical and biomechanical properties of the extracellular matrix (ECM) are crucial in the processes of cell differentiation and proliferation. However, it is unclear to what extent tumor cells are influenced by biomechanical and biophysical changes of the surrounding microenvironment and how this response varies between different tumor forms, and over the course of tumor progression. The entire ensemble of genes encoding the ECM associated proteins is called matrisome. In cancer, the ECM evolves to become highly dysregulated, rigid, and fibrotic, serving both pro-tumorigenic and anti-tumorigenic roles. Tumor desmoplasia is characterized by a dramatic increase of α-smooth muscle actin expressing fibroblast and the deposition of hard ECM containing collagen, fibronectin, proteoglycans, and hyaluronic acid and is common in many solid tumors. In this review, we described the role of inflammation and inflammatory cytokines, in desmoplastic matrix remodeling, tumor state transition driven by microenvironment forces and the signaling pathways in mechanotransduction as potential targeted therapies, focusing on the impact of qualitative and quantitative variations of the ECM on the regulation of tumor development, hypothesizing the presence of matrisome drivers, acting alongside the cell-intrinsic oncogenic drivers, in some stages of neoplastic progression and in some tumor contexts, such as pancreatic carcinoma, breast cancer, lung cancer and mesothelioma.

Electrochemotherapy in Kaposi's Sarcoma Patients: From the Gold Standard Strategy to Locally Advanced Cutaneous and Subcutaneous Lesions.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions.

Management of acute diverticulitis in Stage 0-IIb: indications and risk factors for failure of conservative treatment in a series of 187 patients.

Left-sided acute diverticulitis in WSES Stage 0-IIb preferentially undergoes conservative management. However, there is limited understanding of the risk factors for failure of this approach. The aim of this study was to investigate the factors associated with the decision to perform conservative treatment as well as the predictors of its failure. We included patients with a diagnosis of WSES diverticulitis CT-driven classification Stage 0-IIb treated in the Emergency Surgery Unit of the Agostino Gemelli University Hospital Foundation between 2014 and 2020. The endpoints were the comparison between the characteristics and clinical outcomes of acute diverticulitis patients undergoing conservative versus operative treatment. We also identified predictors of conservative treatment failure. A set of multivariable backward logistic analyses were conducted for this purpose. The study included 187 patients. The choice for operative versus conservative treatment was associated with clinical presentation, older age, higher WSES grade, and previous conservative treatment. There were 21% who failed conservative treatment. Of those, major morbidity and mortality rates were 17.9% and 7.1%, respectively. A previously failed conservative treatment as well as a greater WSES grade and a lower hemoglobin value were significantly associated with failure of conservative treatment. WSES classification and hemoglobin value at admission were the best predictors of failure of conservative treatment. Patients failing conservative treatment had non-negligible morbidity and mortality. These results promote the consideration of a combined approach including baseline patients' characteristics, radiologic features, and laboratory biomarkers to predict conservative treatment failure and therefore optimize treatment of acute diverticulitis.

How to reduce the colorectal anastomotic leakage? The MIRACLe protocol experience in a cohort in a single high-volume centre.

This article reports the results of a novel perioperative treatment implementing the gut microbiota to prevent anastomotic fistula and leakage (AL) in patients undergoing laparoscopic colorectal resections for cancer and represents the continuation of our pilot study on 60 cases. A series of 131 patients underwent elective colorectal surgery at the S. Eugenio Hospital (Rome-Italy) between December 1, 2020, and November 30, 2022, and received a perioperative preparation following the Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) protocol comprising oral antibiotics, mechanical bowel preparation and perioperative probiotics. The results obtained in the MIRACLe group (MG) were compared to those registered in a Control group (CG) of 500 patients operated on between March 2015 and November 30, 2020, who received a standard ERAS protocol. Propensity score-matching (PSM) analysis was performed to overcome patients' selection bias. Patients were categorised according to perioperative preparation (MIRACLe protocol vs standard ERAS protocol) into two groups: 118 patients were in post-matched MIRACLe group (pmMG) and 356 were in post-matched Control group (pmCG). In the pmMG, only 2 anastomotic leaks were registered, and the incidence of AL was just 1.7% vs. 6.5% in the pmCG (p = 0.044). The incidence of surgical site infections (1.7% vs. 3.1%; p = 0.536), reoperations (0.8% vs. 4.2%; p = 0.136) and postoperative mortality (0% vs. 2.0%; p = 0.200) was lower in pmMG. Additionally, the postoperative outcomes were better: the times to first flatus, to first stool and to oral feeding were shorter (1 vs. 2, 2 vs. 3 and 2 vs. 3 days, respectively; p < 0.001). The postoperative recovery was faster, with a shorter time to discharge (5 vs. 6 days; p < 0.001). The MIRACLe protocol was confirmed to be safe and significantly able to reduce anastomotic leaks in patients receiving elective laparoscopic colorectal surgery for cancer.

The role of transanal total mesorectal excision in the treatment of rectal cancer: a systematic review.

INTRODUCTION: Total mesorectal excision (TME) during rectal resection is considered the gold standard for the treatment of rectal cancer. Transanal total mesorectal excision (TaTME) was first described in 2010 and has been applied to humans since 2012 to overcome some of the technical difficulties associated with minimally invasive TMEs. EVIDENCE ACQUSITION: A systematic review of the literature was conducted, and it focused on articles published between 2012 and 2022 to analyze the state of the art of surgical techniques and indications, as well as potential technical, oncological, and functional benefits. EVIDENCE SYNTHESIS: The indications for TaTME are not yet standardized, and structured training programs are necessary to complete a safe learning curve for this new technique. The procedure, when compared with conventional open or minimally invasive TME, is feasible and safe with similar intraoperative and postoperative complications. On the other hand, some new specific complications of this new approach have been described. The short-term pathological and oncologic results are encouraging, especially in terms of the mesorectal specimen quality, distal resection margin and conversion rate. Also, the functional results seem encouraging when compared with other minimally invasive techniques. CONCLUSIONS: Long-term follow-up and ongoing RCT trials are fundamental to evaluate the possible benefits in terms of local recurrence and survival. This will facilitate the comparison with other minimally invasive rectal resections.

Colorectal Cancer: Current Updates and Future Perspectives.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC.

Impact of the COVID-19 Pandemic on Enhanced Recovery After Surgery (ERAS) Application and Outcomes: Analysis in the "Lazio Network" Database.

BACKGROUND: The aim of this study was to investigate how the COVID-19 pandemic influenced ERAS program application in colorectal surgery across hospitals in the Lazio region (central district in Italy) participating in the "Lazio Network" project. METHODS: A multi-institutional database was constructed. All patients included in this study underwent elective colorectal surgery for both malignant and benign disease between January 2019 and December 2020. Emergency procedures were excluded. The population was divided into 2 groups: a pre-COVID-19 group (PG) of patients operated on between February and December 2019 and a COVID-19 group (CG) of patients operated on between February and December 2020, during the first 2 waves of the pandemic in Italy. RESULTS: The groups included 622 patients in the PG and 615 in the CG treated in 8 hospitals of the network. The mean number of items applied was higher in the PG (65.6% vs. 56.6%, p < 0.001) in terms of preoperative items (64.2% vs. 50.7%, p < 0.001), intraoperative items (65.0% vs. 53.3%, p < 0.001), and postoperative items (68.8% vs. 63.2%, p < 0.001). Postoperative recovery was faster in the PG, with a shorter time to first flatus, first stool, autonomous mobilization and discharge (6.82 days vs. 7.43 days, p = 0.021). Postoperative complications, mortality and reoperations were similar among the groups. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the application of ERAS in the centers of the "Lazio Network" study group, with a reduction in adherence to the ERAS protocol in terms of preoperative, intraoperative and postoperative items. In addition, in the CG, the patients had worse postoperative outcomes with respect to recovery and discharge.

Nutritional Support in Cancer patients: update of the Italian Intersociety Working Group practical recommendations.

Malnutrition is a frequent problem in cancer patients, which leads to prolonged and repeated hospitalizations, increased treatment-related toxicity, reduced response to cancer treatment, impaired quality of life, a worse overall prognosis and the avoidable waste of health care resources. Despite being perceived as a limiting factor in oncologic treatments by both oncologists and patients, there is still a considerable gap between need and actual delivery of nutrition care, and attitudes still vary considerably among health care professionals. In the last 5 years, the Italian Intersociety Working Group for Nutritional Support in Cancer Patients (WG), has repeatedly revisited this issue and has concluded that some improvement in nutritional care in Italy has occurred, at least with regard to awareness and institutional activities. In the same period, new international guidelines for the management of malnutrition and cachexia have been released. Despite these valuable initiatives, effective structural strategies and concrete actions aimed at facing the challenging issues of nutritional care in oncology are still needed, requiring the active participation of scientific societies and health authorities. As a continuation of the WG's work, we have reviewed available data present in the literature from January 2016 to September 2021, together with the most recent guidelines issued by scientific societies and health authorities, thus providing an update of the 2016 WG practical recommendations, with suggestions for new areas/issues for possible improvement and implementation.

Enhanced recovery after surgery (ERAS) program in octogenarian patients: a propensity score matching analysis on the "Lazio Network" database.

PURPOSE: The aim of this study was to evaluate the safety and compliance with the enhanced recovery after surgery (ERAS) protocol in octogenarian patients undergoing colorectal surgery in 12 Italian high-volume centers. METHODS: A retrospective analysis was conducted in a consecutive series of patients who underwent elective colorectal surgery between 2016 and 2018. Patients were grouped by age (≥ 80 years vs < 80 years), propensity score matching (PSM) analysis was performed, and the groups were compared regarding clinical outcomes and the mean number of ERAS items applied. RESULTS: Out of 1646 patients identified, 310 were octogenarians. PSM identified 2 cohorts of 125 patients for the comparison of postoperative outcomes and ERAS compliance. The 2 groups were homogeneous regarding the clinical variables and mean number of ERAS items applied (11.3 vs 11.9, p-ns); however, the application of intraoperative items was greater in nonelderly patients (p 0.004). The functional recovery was similar between the two groups, as were the rates of postoperative severe complications and 30-day mortality rate. Elderly patients had more overall complications. Furthermore, the mean hospital stay was higher in the elderly group (p 0.027). Multivariable analyses documented that postoperative stay was inversely correlated with the number of ERAS items applied (p < 0.0001), whereas age ≥ 80 years significantly correlated with the overall complication rate (p 0.0419). CONCLUSION: The ERAS protocol is safe in octogenarian patients, with similar levels of compliance and surgical outcomes. However, octogenarian patients have a higher rate of overall complications and a longer hospital stay than do younger patients.

Implementation of the gut microbiota prevents anastomotic leaks in laparoscopic colorectal surgery for cancer:the results of the MIRACLe study.

The aim of this pilot study was to evaluate the effects of a novel perioperative treatment for the implementation of the gut microbiota, to prevent anastomotic fistula and leakage (AL) in patients undergoing laparoscopic colorectal resections for cancer. A series of 60 patients who underwent elective colorectal surgery at S. Eugenio Hospital (Rome-Italy) between December 1, 2020 and November 30, 2021 and received a novel perioperative preparation following the MIRACLe (Microbiota Implementation to Reduce Anastomotic Colorectal Leaks) protocol (oral antibiotics, mechanical bowel preparation and perioperative probiotics), was compared to a group of 500 patients (control group) operated on between March 2015 and November 30, 2020, who received a standard ERAS protocol. In the MIRACLe Group only 1 anastomotic leak was registered. In this group the incidence of AL was just 1.7% vs. 6.4% in the control group (p = 0.238) and the incidence of surgical site infections (1.7% vs. 3.6%; p = 0.686), reoperations (1.7% vs. 4.2%; p = 0.547) and postoperative mortality (0% vs. 2.2%; p = 0.504) were lower. The postoperative outcomes were also better: the times to first flatus, to first stool and to oral feeding were shorter (1 vs. 2, 2 vs. 3 and 2 vs. 3 days, respectively; p < 0.001). Additionally, the postoperative recovery was faster, with a shorter time to discharge (4 vs. 6 days; p < 0.001). In this pilot study, the MIRACLe protocol appeared to be safe and considerably reduced anastomotic leaks in elective laparoscopic colorectal surgery for cancer, even if not statistically significant, due to the small number of cases.

Nutritional support in surgical oncology: A survey by SICO in collaboration with the Intersociety Italian Working Group for Nutritional Support in Cancer Patients.

PURPOSE: Nutritional support is a keystone component in perioperative care in patients undergoing oncological surgery with a direct impact on surgical outcomes. This study aimed to evaluate how nutritional support in the surgical setting is managed and applied in Italian hospitals. METHODS: A national survey was designed by the Italian Society of Surgical Oncology (SICO) and disseminated in early 2021. The results were analyzed for the entire population and for comparing the following different subgroups: northern vs. southern regions; high-volume vs. low-volume centers; and junior vs. senior surgeons. RESULTS: Out of the 141 responses collected from all Italian regions, 43.2% of the participants worked in a surgical unit where nutritional status evaluations and interventions were not routinely practiced, although the key features (nutritional counseling, oral supplementation, enteral and parenteral nutrition) were available in 77.3% of the hospitals. Among the participating centers, the ERAS protocol was systematically applied in only 29.5% of cases, and in 25.5% of cases, most of the items were followed, although not systematically. Among the surgeons who practiced in compliance with the ERAS pathways, almost half of the participants declared that the protocol was applied only for low-risk patients. No significant differences were documented when comparing Italian regions, high-volume vs. low-volume institutions or junior vs. senior participants. CONCLUSION: Nutritional support in oncological surgery is frequently neglected in Italian hospitals, regardless of the geographic distribution and volumes of the institutions. A cultural change and an improvement in the availability of nutritional services are needed for widespread implementation.

Laparoscopic right colectomy: changes in surgical technique and perioperative management allow better postoperative results in a comparative series of 361 patients.

To compare the short-term outcomes in patients who underwent laparoscopic right colectomy with a traditional minimally invasive approach versus patients who underwent a laparoscopic colectomy with an enhanced perioperative pathway. A retrospective analysis was conducted on a consecutive series of patients who underwent elective laparoscopic right colectomy for neoplastic disease between January 1, 2011 and December 31, 2020. The patients were divided into two groups: the first cohort (FC), who underwent a traditional laparoscopic colectomy, mainly with extracorporeal anastomosis, between January 1, 2011 and December 31, 2015 and the second cohort (SC), who underwent a laparoscopic colectomy with an enhanced intraoperative (intracorporeal anastomosis) and perioperative pathway (ERAS protocol) between January 1, 2016 and December 31, 2020. There were a total of 361 patients, including 177 in the FC and 184 in the SC. In the SC a higher number of intracorporeal anastomoses was performed (91.8% vs. 19.2%, p < 0.001), drains were placed in 42 patients only (22.8% vs. 100% in the FC) and nasogastric tubes were placed in 21 patients only (11.4% vs. 100% in the FC). In the initial period of the SC. the procedures required a slightly longer operative time (median 105 vs. 95 min; p = 0.002), but postoperative surgical complications were lower (12% vs. 17.4%, p = 0.179). Postoperative recovery was faster in SC along with time to discharge (4 vs. 7 days; p < 0.001). Intraoperative anastomosis and enhanced pathways in right laparoscopic colectomy seem to guarantee better results with lower surgical complications and faster postoperative recovery.

Surgical Training for Transanal Total Mesorectal Excision in a Live Animal Model: A Preliminary Experience.

Background: In this preliminary experience, the feasibility and effectiveness of surgical training with an animal model for transanal total mesorectal excision (TaTME) were evaluated. Methods: The training was conducted in two experimental animal laboratories in Italy authorized by the Italian Ministry of Health, using female Danish Landrace pigs under the supervision of surgeons with extensive experience in TaTME, animal laboratory training and cadaver laboratory training. The procedure was divided into separate steps, and all the participants were guided step-by-step throughout the entirety of the procedure. Results: During all the editions of the animal laboratory, all the procedures were completed with no major damage to the anatomical structures or intraoperative death of the animals. Live animal tissue is very similar to human tissue, helping trainees improve their tactile feedback. The bleeding effect improved the value of the training and taught the participants how to address this complication. The lack of mesorectal tissue in pigs compared with humans was the main difference. Animal laboratories should not be considered alternatives to cadaver laboratories but as complementary training activities due to their effectiveness and lower costs. Conclusions: Surgical training in animal models for TaTME seems to be effective and could be an opportunity to improve training alongside the use of a cadaver laboratory and proctoring.

Dynamics and genetic regulation of leaf nutrient concentration in barley based on hyperspectral imaging and machine learning.

Biofortification, the enrichment of nutrients in crop plants, is of increasing importance to improve human health. The wild barley nested association mapping (NAM) population HEB-25 was developed to improve agronomic traits including nutrient concentration. Here, we evaluated the potential of high-throughput hyperspectral imaging in HEB-25 to predict leaf concentration of 15 mineral nutrients, sampled from two field experiments and four developmental stages. Particularly accurate predictions were obtained by partial least squares regression (PLS) modeling of leaf concentrations for N, P and K reaching coefficients of determination of 0.90, 0.75 and 0.89, respectively. We recognized nutrient-specific patterns of variation of leaf nutrient concentration between developmental stages. A number of quantitative trait loci (QTL) associated with the simultaneous expression of leaf nutrients were detected, indicating their potential co-regulation in barley. For example, the wild barley allele of QTL-4H-1 simultaneously increased leaf concentration of N, P, K and Cu. Similar effects of the same QTL were previously reported for nutrient concentrations in grains, supporting a potential parallel regulation of N, P, K and Cu in leaves and grains of HEB-25. Our study provides a new approach for nutrient assessment in large-scale field experiments to ultimately select genes and genotypes supporting plant biofortification.

INDICATIONS FOR LIMITATIONS OF THE OMENTAL PEDICLE FLAP IN IMMEDIATE BREAST RECONSTRUCTION - SURGICAL RESULTS EVALUATION AND BREAST-Q© 2.0 SURVEY.

BACKGROUND AND AIM: Immediate reconstruction with an omental flap is a recognized suitable method for a full-thickness breast reconstruction or implant coverage for well-selected cases of nipple or skin-sparing mastectomies as well as cases of skin-reducing mastectomies. The authors' aim is the evaluation of indications and limitations of this technique with an original approach and also based on the analysis of patients' global satisfaction using the BREAST-Q 2.0© survey. MATERIALS AND METHODS: From January 2014 to March 2018, 12 women aged between 29 to 67 years old (mean age: 49 years) underwent immediate breast reconstruction alone or with a definitive implant covered by a pedicled omental flap. All of them were asked to fill out the BREAST-Q© 2.0 survey. CONCLUSIONS: The careful analysis of the cases shows that the indications for the immediate breast reconstruction based on the omental flap with a minimal resulting donor-site morbidity are strictly linked to its limitations, which are correctly reported in the study, but in the same way, it suggests that patients who underwent implant-based immediate breast reconstruction with omental flap reported significant improvements in satisfaction and health-related quality of their life.

High-pressure CO2 insufflation is a risk factor for postoperative ileus in patients undergoing TaTME.

The aim of this study is to evaluate the influence of high-pressure CO2 insufflation during TaTME on the occurrence of postoperative ileus. All patients undergoing elective transanal total mesorectal excision (TaTME) between April 2015 and March 2019 were included in a prospective database. Eligible patients were adults with mid and low-level rectal cancer undergoing elective TaTME with colorectal anastomosis and diverting ileostomy, following a standardized ERAS pathway. Patients were divided into a low-pressure (LP) group, where surgery was performed with an intrabdominal CO2 pressure of 12 mmHg, and a high-pressure (HP) group, where the intrabdominal pressure reached 15 mmHg of CO2 once the two surgical fields were connected. Of 98 patients undergoing TaTME in the observed period, 74 met the inclusion criteria and were included in this study. There was no significant difference in postoperative complications between the LP and HP groups, except for postoperative ileus, which occurred in seven patients (13.2%) in the LP group and seven patients (33.3%) in the HP group (p value 0.046). The logistic multivariate analysis showed that a high intraabdominal CO2 pressure (OR 7040, 95% CI 1591-31,164, p value 0.01) and male sex (OR 10,343, 95% CI 1078-99,256, p value 0.043) were significantly associated with postoperative ileus after TaTME. Intraabdominal CO2 pressure should be carefully set, as it may represent a risk factor for postoperative ileus in patients undergoing TaTME.

Eccrine porocarcinoma: case report and review of the literature.

Eccrine porocarcinoma is a rare skin cancer that originates from the acrosyringium of eccrine sweat glands. From the clinical point of view the differential diagnosis with other skin cancers such as basal cell carcinoma and squamous cell carcinoma it is often impossible, only the histopathologic features can lead to the definitive diagnosis. Eccrine porocarcinoma can arise from a previous poroma or de novo, it may recur after surgical excision and cause lymph node and visceral metastasis. There are no international guidelines for treatment or follow-up of patients. The aim of this work was to present a rare case of eccrine porocarcinoma of the scalp successfully treated in our clinic and to extrapolate from the international literature the main clinical and histopathological features of eccrine porocarcinoma and the various experiences regarding the types of treatment.

Global updates in the treatment of gastric cancer: a systematic review. Part 2: perioperative management, multimodal therapies, new technologies, standardization of the surgical treatment and educational aspects.

Gastric cancer is the fifth malignancy and the third cause of cancer death worldwide, according to the global cancer statistics presented in 2018. Its definition and staging have been revised in the eight edition of the AJCC/TNM classification, which took effect in 2018. Novel molecular classifications for GC have been recently established and the process of translating these classifications into clinical practice is ongoing. The cornerstone of GC treatment is surgical, in a context of multimodal therapy. Surgical treatment is being standardized, and is evolving according to new anatomical concepts and to the recent technological developments. This is leading to a massive improvement in the use of mini-invasive techniques. Mini-invasive techniques aim to be equivalent to open surgery from an oncologic point of view, with better short-term outcomes. The persecution of better short-term outcomes also includes the optimization of the perioperative management, which is being implemented on large scale according to the enhanced recovery after surgery principles. In the era of precision medicine, multimodal treatment is also evolving. The long-time-awaited results of many trials investigating the role for preoperative and postoperative management have been published, changing the clinical practice. Novel investigations focused both on traditional chemotherapeutic regimens and targeted therapies are currently ongoing. Modern platforms increase the possibility for further standardization of the different treatments, promote the use of big data and open new possibilities for surgical learning. This systematic review in two parts assesses all the current updates in GC treatment.