Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study.

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Colonic Resection, Stoma, or Self-expanding Metal Stents for Obstructive Left Colon Cancer: the CROSCO-1 study protocol.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. There are several causes of a mechanical left bowel obstructive but CRC accounts for approximately 50% of cases and in 10-30% of whom it is the presenting syndrome. In most cases, the left colon is involved. At present, the range of therapeutic alternatives in the management of obstructive left CRC in emergency conditions (primary resection vs. staged resection with applied self-expanding metallic stents) is broad, whereas internationally validated clinical recommendations in each condition are still lacking. This enormous variability affects the scientific evidence on both the immediate and long-term surgical and oncological outcomes. METHODS: CROSCO-1 (Colonic Resection, Stoma or Self-expanding Metal Stents for Obstructive Left Colon Cancer) study is a national, multi-center, prospective observational study intending to compare the clinical results of all these therapeutic regimens in a cohort of patients treated for obstructive left-sided CRC. RESULTS: The primary aim of the CROSCO-1 study is the 1-year stoma rate of patients undergoing primary emergency surgical resection (Hartmann procedure or primary resection and anastomosis) compared with patients undergoing staged resection. Secondary outcomes are 30-day and 90-day major morbidity and mortality, 1-year quality of life and the timing of chemotherapy initiation in the two groups. Future CROSCO studies will follow in which, instead, we will evaluate the long-term oncological outcomes of the two treatment strategies. CONCLUSIONS: The results of a large prospective cohort study which will analyze what really happens in the common clinical practice of managing patients with obstructive left CRC will have the aim of understanding which is the best strategy in terms of surgical and oncological outcomes. Indeed, the CROSCO-1 study will analyze the early surgical outcomes for patients with obstructed left CRC. Future CROSCO studies will follow in which, instead, we will evaluate the long-term oncological outcomes of the two treatment strategies.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study.

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients: the Italian Society of Emergency Surgery and Trauma (SICUT) guidelines.

Dealing with acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients is frequent during daily practice and requires complex management. Several procedures exist to postpone and/or prevent surgical intervention in those patients who temporarily or definitively cannot undergo surgery. After a systematic review of the literature, an expert panel from the Italian Society of Emergency Surgery and Trauma (SICUT) discussed the different issues and statements in subsequent rounds. The final version of the statements was discussed during the annual meeting in Rome (September 2022). The present paper presents the definitive conclusions of the discussion. Fifteen statements based on the literature evidence were provided. The statements gave precise indications regarding the decisional process and the management of patients who cannot temporarily or definitively undergo cholecystectomy for acute cholecystitis. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients should be multidisciplinary. The different gallbladder drainage methods must be tailored according to each patient and based on the expertise of the hospital. Percutaneous gallbladder drainage is recommended as the first choice as a bridge to surgery or in severely physiologically deranged patients. Endoscopic gallbladder drainage (cholecystoduodenostomy and cholecystogastrostomy) is suggested as a second-line alternative especially as a definitive procedure for those patients not amenable to surgical management. Trans-papillary gallbladder drainage is the last option to be reserved only to those unfit for other techniques. Delayed laparoscopic cholecystectomy in patients with percutaneous gallbladder drainage is suggested in all those patients recovering from the conditions that previously discouraged surgical intervention after at least 6 weeks from the gallbladder drainage.

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.

The burden of the knowledge-to-action gap in acute appendicitis.

BACKGROUND: The burden of emergency general surgery (EGS) is higher compared to elective surgery. Acute appendicitis (AA) is one of the most frequent diseases and its management is dictated by published international clinical practice guidelines (CPG). Adherence to CPG has been reported as heterogeneous. Barriers to clinical implementation were not studied. This study explored barriers to adherence to CPG and the clinico-economic impact of poor compliance. METHODS: Data were extracted from the three-year data lock of the REsiDENT-1 registry, a prospective resident-led multicenter trial. We identified 7 items from CPG published from the European Association of Endoscopic Surgery (EAES) and the World Society of Emergency Surgery (WSES). We applied our classification proposal and used a five-point Likert scale (Ls) to assess laparoscopic appendectomy (LA) difficulty. Descriptive analyses were performed to explore compliance and group comparisons to assess the impact on outcomes and related costs. We ran logistic regressions to identify barriers and facilitators to implementation of CPG. RESULTS: From 2019 to 2022, 653 LA were included from 24 centers. 69 residents performed and coordinated data collection. We identified low compliance with recommendations on peritoneal irrigation (PI) (25.73%), abdominal drains (AD) (34.68%), and antibiotic stewardship (34.17%). Poor compliance on PI and AD was associated to higher infectious complications in uncomplicated AA. Hospitalizations were significantly longer in non-compliance except for PI in uncomplicated AA, and costs significantly higher, exception made for antibiotic stewardship in complicated AA. The strongest barriers to CPG implementation were complicated AA and technically challenging LA for PI and AD. Longer operative times and the use of PI negatively affected antibiotic stewardship in uncomplicated AA. Compliance was higher in teaching hospitals and in emergency surgery units. CONCLUSIONS: We confirmed low compliance with standardized items influenced by environmental factors and non-evidence-based practices in complex LA. Antibiotic stewardship is sub-optimal. Not following CPG may not influence clinical complications but has an impact in terms of logistics, costs and on the non-measurable magnitude of antibiotic resistance. Structured educational interventions and institutional bundles are required.

Guidelines for the Treatment of Abdominal Abscesses in Acute Diverticulitis: An Umbrella Review.

BACKGROUND: This systematic umbrella review aims to investigate and provide an analysis of guidelines regarding the treatment of diverticular abscesses. MATERIAL AND METHODS: A systematic literature search was performed using the Cochrane Overviews of Reviews model and the 'Clinical Practice Guidelines'; at the end of initial search, only 12 guidelines were included in this analysis. The quality of the guidelines was assessed by adopting the "Appraisal of Guidelines for Research and Evaluation II" (AGREE II). The comparative analysis of these guidelines has highlighted the presence of some differences regarding the recommendations on the treatment of diverticular abscesses. In particular, there are some controversies about the diameter of abscess to be used in order to decide between medical treatment and percutaneous drainage. Different guidelines propose different abscess diameter cutoffs, such as 3 cm, 4-5 cm, or 4 cm, for distinguishing between small and large abscesses. CONCLUSIONS: Currently, different scientific societies recommend that diverticular abscesses with diameters larger than 3 cm should be considered for percutaneous drainage whereas abscesses with diameters smaller than 3 cm could be appropriately treated by medical therapy with antibiotics; only a few guidelines suggest the use of percutaneous drainage for abscesses with a diameter greater than 4 cm. The differences among guidelines are the consequence of the different selection of scientific evidence. In conclusion, our evaluation has revealed the importance of seeking new scientific evidence with higher quality to either confirm, reinforce or potentially weaken the existing recommendations from different societies.

Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study.

Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.

A Hypothetical New Challenging Use for Indocyanine Green Fluorescence during Laparoscopic Appendectomy: A Mini-Series of Our Experience and Literary Review.

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department with an usual range of symptoms for acute appendicitis. The patients were successfully managed by fully LA with the help of a new hypothetical challenging use of ICG-FA.

Management of Acute Cholecystitis in High-Risk Patients: Percutaneous Gallbladder Drainage as a Definitive Treatment vs. Emergency Cholecystectomy-Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review aims to investigate whether percutaneous transhepatic gallbladder biliary drainage (PTGBD) is superior to emergency cholecystectomy (EC) as a definitive treatment in high-risk patients with acute cholecystitis (AC). MATERIAL AND METHODS: A systematic literature search was performed until December 2022 using the Scopus, Medline/PubMed and Web of Science databases. RESULTS: Seventeen studies have been included with a total of 783,672 patients (32,634 treated with PTGBD vs. 4663 who underwent laparoscopic cholecystectomy, 343 who had open cholecystectomy and 746,032 who had some form of cholecystectomy, but without laparoscopic or open approach being specified). An analysis of the results shows that PTGBD, despite being less invasive, is not associated with lower morbidity with respect to EC (RR 0.77 95% CI [0.44 to 1.34]; I2 = 99%; p = 0.36). A lower postoperative mortality was reported in patients who underwent EC (2.37%) with respect to the PTGBD group (13.78%) (RR 4.21; 95% CI [2.69 to 6.58]; p < 0.00001); furthermore, the risk of hospital readmission for biliary complications (RR 2.19 95% CI [1.72 to 2.79]; I2 = 48%; p < 0.00001) and hospital stay (MD 4.29 95% CI [2.40 to 6.19]; p < 0.00001) were lower in the EC group. CONCLUSIONS: In our systematic review, the majority of studies have very low-quality evidence and more RCTs are needed; furthermore, PTGBD is inferior in the treatment of AC in high-risk patients. The definition of high-risk patients is important in interpreting the results, but the methods of assessment and definitions differ between studies. The results of our systematic review and meta-analysis failed to demonstrate any advantage of using PTGBD over ER as a definitive treatment of AC in critically ill patients, which suggests that EC should be considered as the treatment of choice even in very high-risk patients. Most likely, the inferiority of PTGBD versus early LC for high-risk patients is related to an association of various patient-side factor conditions and the severity of acute cholecystitis.

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.

Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study.

INTRODUCTION: Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. MATERIALS AND METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. RESULTS: Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). CONCLUSION: In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy.

Discontinuity of marginal artery at splenic flexure and rectosigmoid junction: A systematic review and meta-analysis.

AIM: The aim of this study was to provide comprehensive evidence-based assessment of the discontinuity of the marginal artery at the splenic flexure (SF) and the rectosigmoid junction (RSJ). METHOD: A systematic review was conducted of literature published to 26 December 2022 in the electronic databases PubMed, SCOPUS and Web of Science to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using the Metafor package in R. The primary outcomes were the pooled PPEs of the marginal artery at the SF and the RSJ. The secondary outcome was the size of vascular anastomoses. RESULTS: A total of 21 studies (n = 2,864 patients) were included. The marginal artery was present at the splenic flexure in 82% (95% CI: 62-95) of patients. Approximately 81% (95% CI: 63-94%) of patients had a large macroscopic anastomosis, while the remainder (19%) had small bridging ramifications forming the vessel. The marginal artery was present at the RSJ in 82% (95% CI: 70-91%) of patients. CONCLUSION: The marginal artery may be absent at the SF and the RSJ in up to 18% of individuals, which may confer a higher risk of ischaemic colitis. As a result of high interstudy heterogeneity noted in our analysis, further well-powered studies to clarify the prevalence of the marginal artery at the SF and the RSJ, as well as its relationship with other complementary colonic collaterals (intermediate and central mesenteric), are warranted.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

Cortical atrophy in chronic subdural hematoma from ultra-structures to physical properties.

Several theories have tried to elucidate the mechanisms behind the pathophysiology of chronic subdural hematoma (CSDH). However, this process is complex and remains mostly unknown. In this study we performed a retrospective randomised analysis comparing the cortical atrophy of 190 patients with unilateral CSDH, with 190 healthy controls. To evaluate the extent of cortical atrophy, CT scan images were utilised to develop an index that is the ratio of the maximum diameter sum of 3 cisterns divided by the maximum diameter of the skull at the temporal lobe level. Also, we reported, for the first time, the ultrastructural analyses of the CSDH using a combination of immunohistochemistry methods and transmission electron microscopy techniques. Internal validation was performed to confirm the assessment of the different degrees of cortical atrophy. Relative Cortical Atrophy Index (RCA index) refers to the sum of the maximum diameter of three cisterns (insular cistern, longitudinal cerebral fissure and cerebral sulci greatest) with the temporal bones' greatest internal distance. This index, strongly related to age in healthy controls, is positively correlated to the preoperative and post-operative maximum diameter of hematoma and the midline shift in CSDH patients. On the contrary, it negatively correlates to the Karnofsky Performance Status (KPS). The Area Under the Receiver Operating Characteristics (AUROC) showed that RCA index effectively differentiated cases from controls. Immunohistochemistry analysis showed that the newly formed CD-31 positive microvessels are higher in number than the CD34-positive microvessels in the CSDH inner membrane than in the outer membrane. Ultrastructural observations highlight the presence of a chronic inflammatory state mainly in the CSDH inner membrane. Integrating these results, we have obtained an etiopathogenetic model of CSDH. Cortical atrophy appears to be the triggering factor activating the cascade of transendothelial cellular filtration, inflammation, membrane formation and neovascularisation leading to the CSDH formation.

High-resolution anoscopy predictive modeling of anal canal cancer response after definitive chemoradiotherapy in COVID19 era.

PURPOSE: To develop a predictive index model, integrating both clinical and high-resolution anoscopy (HRA) features to further personalize the decision making process in anal canal carcinoma in COVID19 era. METHODS AND MATERIALS: We assess HRA parameters after definitive chemoradiotherapy in patients with anal canal malignant lesions. RESULTS: HRA features could be important to assess the effect of CRT and a risk stratification system should be introduced in clinical practice to better allocate therapeutic interventions. CONCLUSION: To our knowledge this is the first proposal for HRA findings in anal canal cancer after definitive CRT. We believe that a risk score can be useful to estimate the risk of treatment failure (in term of persistence disease and/or recurrence) and its clinical relevance should not to be underestimated.

Percutaneous cholecystostomy as bridge to surgery vs surgery in unfit patients with acute calculous cholecystitis: A systematic review and meta-analysis.

BACKGROUND: Acute cholecystitis is one of the most common causes of acute abdomen. Early laparoscopic cholecystectomy is the gold standard treatment, still burdened by a risk of intraoperative biliary duct injury. An alternative strategy to manage patients with severe acute cholecystitis is the percutaneous gallbladder drainage (PGBD). METHODS: The Italian Society of Emergency Surgery and Trauma performed a systematic review and meta-analysis with the aim to clarify controversies about the preoperative use of PGBD. We extracted 32 studies: 9 Randomized Control Trial Studies (RCTs) and 23 no RCTs. RESULTS OF CRITICAL OUTCOMES: The incidence of post-operative complications was lower in the PGBD associated at LC than in the LC alone (RCTs: RR 0.28, 95% CI 0.14 to 0.56, I2 = 63%). The incidence of the post-operative biliary leakage was higher in late PGBD' group (RCTs: RR 0.18, 95% CI 0.04 to 0.80). RESULTS OF OTHER OUTCOMES: The incidence of intraabdominal abscess, blood loss, conversion to open, subtotal cholecystectomy, operative time and wound infection was lower in PGBD' group. The total hospital stay was the same. CONCLUSION: A strong recommendation is performed to the use of the PGBD + LC than upfront LC to reduce biliary leakage (recommendation "strong positive") in high risk acute cholecystitis especially in patients with higher perioperative risks or longstanding acute cholecystitis. For post-operative complications a recommendation "positive weak" suggests that PGBD + LC could be used than upfront LC to reduce the rate of post-operative complications.

Regenerative Medicine to Improve Outcomes of Ventral Hernia Reconstruction (REPAIR Study) Phase 1: Find the Best Decellularization Protocol for the Human Dermis.

Background: Tissue regeneration is a complex process that allows wounds to heal. Many options are currently available to help human skin repair and to reduce the recurrence of hernias. The aim of this study is to analyze the best decellularization protocol for allogenic human dermal tissues. Methods: Dermal flaps from donors were used and compared with a control group. Each flap was subjected to seven different decellularization protocols and washed with a sequence of five solutions. The samples were then subjected to four control tests (such as Nile Red), and long-term contacts were analyzed to assess whether the decellularized dermis samples could support the growth of human fibroblasts. Results: All the samples had an average residual viability of 60%. Except for one sample, the decellularization treatments were able to reduce cell viability significantly. The Nile Red test showed a significant reduction in phospholipid content (mean 90%, p-value < 0.05) in all treatments. The cell growth increased in a linear manner. As described in the literature, sodium-dodecyl-sulfate (SDS) caused an interference between the test and the detergent. Conclusions: This paper shows the first step to finding the best decellularization protocol for allografting human dermal tissues. Further biocompatibility tests and DNA quantification are necessary.

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.