HOSPITAL ADMISSION, MEDICAL, AND SURGICAL PROCEDURES FOR ACUTE DIVERTICULITIS ARE MORE APPROPRIATE WHEN USING A DIAGNOSTIC AND THERAPEUTIC ASSISTANCE PATHWAY: AN EXPERIENCE FROM A REFERRAL CENTRE.

IIntroduction: Our aim was to assess the impact of the Diagnostic and Therapeutic Assistance Pathway (PDTA) developed for acute diverticulitis (AD) on the management of patients with AD and referring to the emergency Room (ER) in a referral centre. METHODS: This retrospective study includes all patients diagnosed with AD and referring to the ER between January 1st 2021 and December 31st 2022 (after approval of PDTA), compared to the same period of 2015-2019. Length of stay in ER, medical and surgical management, and lenght in hospital stay (in days) were also measured according to the type of disease (uncomplicated vs. complicated). RESULTS: ER admission due to AD during the period 2015-2019 was 240±13 cases per year, while it was 290 cases in 2022 (p=0.05). After adopting the PDTA, the rate of lenght of stay in ER >24h for AD was significantly reduced (p=0.01); the median rate of hospital admission for AD was significantly reduced (p<0.05); the rate of medical treatment of uncomplicated disease was increased (p=0.01), while the rate of surgical management was decreased (p=0.05); the rate of medical treatment of complicated disease was increased (p=0.01), while the rate of surgical management was decreased (p=0.001); the hospital stay was significantly reduced both in uncomplicated (p=0.05) and uncomplicated (p=0.05) AD. CONCLUSIONS: The development and the routinely use of a PDTA dedicated to AD has significantly improved the management of these patients, reducing the ER stay, the surgical procedures and the overall hospital stay.

The Impact of Post-Pancreatectomy Acute Pancreatitis (PPAP) on Long-Term Outcomes after Pancreaticoduodenectomy: A Single-Center Propensity-Score-Matched Analysis According to the International Study Group of Pancreatic Surgery (ISGPS) Definition.

Post-pancreatectomy acute pancreatitis (PPAP) is a potentially life-threating complication. Although multiple authors demonstrated PPAP as a predisposing feature for a more detrimental clinical course, no evidence is currently present on its potential impact on long-term outcomes. The aim of this study is to evaluate how PPAP onset may influence overall (OS) and disease-free survival (DSF) after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Patients who underwent PD for PDAC from 2006 to 2021 were enrolled. PPAP was defined according to the International Study Group of Pancreatic Surgery (ISGPS) definition. Propensity score matching (PSM) was performed in order to reduce potential selection biases. After PSM, 32 patients out of 231 PDs who developed PPAP (PPAP group) were matched to 32 patients who did not present PPAP (no-PPAP group). PPAP patients more frequently presented major post-operative complications (p = 0.02) and post-operative pancreatic fistula (POPF) (p = 0.003). Median follow-up was 26.2 months, with no difference between the two groups (p = 0.79). A comparable rate of local or distant metastases was noted in the two cohorts (p = 0.2). Five-year OS was comparable between the two populations (39.3% and 35.7% for the no-PPAP and PPAP populations, respectively; p = 0.53). Conversely, despite not being statistically significant, a worse 5-year DFS was evidenced in the case of PPAP (23.2%) as compared to the absence of PPAP (37.4%) (p = 0.51). With the limitations due to the small sample size, PPAP may potentially relate to worse long-term outcomes in terms of DFS. However, further studies with wider study populations are still needed in order to better clarify the prognostic role of PPAP.

The Role of Microbiota in Pancreatic Cancer.

Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients' responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota-including the gut, pancreatic, and oral microbiota-in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease.

The role of the multidisciplinary tumor board (MDTB) in the assessment of pancreatic cancer diagnosis and resectability: A tertiary referral center experience.

Background: The introduction of multidisciplinary tumor boards (MDTBs) for the diagnostic and therapeutic pathway of several oncological disease significantly ameliorated patients' outcomes. However, only few evidences are currently present on the potential impact of the MDTB on pancreatic cancer (PC) management. Aim of this study is to report how MDTB may influence PC diagnosis and treatment, with particular focus on PC resectability assessment and the correspondence between MDTB definition of resectability and intraoperative findings. Methods: All patients with a proven or suspected diagnosis of PC discussed at the MDTB between 2018 and 2020 were included in the study. An evaluation of diagnosis, tumor response to oncological/radiation therapy and resectability before and after the MDTB was conducted. Moreover, a comparison between the MDTB resectability assessment and the intraoperative findings was performed. Results: A total of 487 cases were included in the analysis: 228 (46.8%) for diagnosis evaluation, 75 (15.4%) for tumor response assessment after/during medical treatment, 184 (37.8%) for PC resectability assessment. As a whole, MDTB led to a change in treatment management in 89 cases (18.3%): 31/228 (13.6%) in the diagnosis group, 13/75 (17.3%) in the assessment of treatment response cohort and 45/184 (24.4%) in the PC resectability evaluation group. As a whole, 129 patients were given indication to surgery. Surgical resection was accomplished in 121 patients (93.7%), with a concordance rate of resectability between MDTB discussion and intraoperative findings of 91.5%. Concordance rate was 99% for resectable lesions and 64.3% for borderline PCs. Conclusions: MDTB discussion consistently influences PC management, with significant variations in terms of diagnosis, tumor response assessment and resectability. In this last regard, MDTB discussion plays a key role, as demonstrated by the high concordance rate between MDTB resectability definition and intraoperative findings.

Ulcerative Colitis After Complicated Diverticulitis.

It has been recently shown that inflammatory bowel disease may follow an episode of acute complicated diverticulitis. We report 3 cases of ulcerative colitis after acute complicated diverticulitis that required surgery. All cases occurred in elderly patients with moderate-to-severe disease and 1 individual who also received treatment with biologics. These cases highlight the need for older patients to be strictly monitored after an episode of perforated diverticulitis requiring surgery because of the risk of developing ulcerative colitis.

Acute pancreatitis after pancreatoduodenectomy: clinical outcomes and predictive factors analysis according to the International Study Group of Pancreatic Surgery definition.

BACKGROUND: Post-pancreatectomy acute pancreatitis (PPAP) is an increasingly described complication after pancreatic resection. No uniform definition criteria were present in the literature until the recent proposal of the International Study Group of Pancreatic Surgery (ISGPS). Aim of this study is to evaluate the clinical significance of the novel ISGPS definition of PPAP. METHODS: Patients who underwent pancreatoduodenectomy (PD) between 2006 and 2022 were enrolled. PPAP was defined and graded according to the ISGPS criteria. RESULTS: Among 520 PDs, 120 (23%)patients developed post-operative hyperamylasemia (POH), while PPAP occurred in 63(12.1%) cases. PPAP occurrence related to a higher rate of more severe complications (48-76.1%vs118-25.8%; p < 0.0001), delayed gastric emptying (DGE) (27-42.9%vd114-24.9%; p = 0.003) and post-operative pancreatic fistula (POPF) (57-90.5%vs186-40.8%; p < 0.0001). When stratified for PPAP severity, grade B and C patients more frequently developed major complications (p < 0.0001), POPF (p < 0.0001), DGE (p = 0.02) and post-operative hemorrhage (p < 0.0001) as compared to POH. At the multivariable analysis, soft pancreatic texture (p = 0.01)and a Wirsung diameter ≤3 mm (p = 0.01) were recognized as prognostic factors for PPAP onset, while a pancreatic duct ≤3 mm was the only feature significantly influencing a more severe course of PPAP (p = 0.01). CONCLUSION: The ISGPS classification is confirmed as a valuable method for a uniform definition and clinical course evaluation. Further studies in a prospective manner are still needed for a further confirmation.

Microbiota Composition in Diverticular Disease: Implications for Therapy.

Gut microbiota (GM) composition and its imbalance are crucial in the pathogenesis of several diseases, mainly those affecting the gastrointestinal tract. Colon diverticulosis and its clinical manifestations (diverticular disease, DD) are among the most common digestive disorders in developed countries. In recent literature, the role of GM imbalance in the onset of the different manifestations within the clinical spectrum of DD has been highlighted. This narrative review aims to summarize and critically analyze the current knowledge on GM dysbiosis in diverticulosis and DD by comparing the available data with those found in inflammatory bowel disease (IBD). The rationale for using probiotics to rebalance dysbiosis in DD is also discussed.

Preliminary evaluation of two-row versus three-row circular staplers for colorectal anastomosis after rectal resection: a single-center retrospective analysis.

PURPOSE: Circular staplers for colorectal anastomoses significantly ameliorated post-operative outcomes after rectal resection. The more recent three-row technology was conceived to improve anastomotic resistance and, thus, lower the incidence of anastomotic complications. The aim of this study was to evaluate potential advantages of three-row circular staplers (Three-CS) on anastomotic leakage (AL), stenosis (AS), and hemorrhage (AH) rates after rectal resection as compared to two-row circular staplers (Two-CS). METHODS: All rectal resections for rectal cancer between 2016 and 2021 were retrospectively included. Patients were classified according to the circular stapler employed in Two-CS and Three-CS cohorts. AL, AS, and AH rates were compared between the two populations. Additionally, the prognostic role of the type of circular stapler on AL onset was evaluated. RESULTS: Three-hundred and seventy-five patients underwent a rectal resection with an end-to-end anastomosis during the study period: 197 constituted the Two-CS group and 178 the Three-CS cohort. AL rate was 6.7%, significantly higher in the Two-CS group (19-9.6%) as compared to the Three-CS cohort (6-3.4%) (p = 0.01). No difference was noted in terms of AL severity. Although not statistically significant, a lower incidence rate of AL was evidenced even in the subset of patients with low rectal cancers (4.5% vs 12.5% in the two-row cohort; p = 0.33). At the multivariate analysis, Two-CS was a negative prognostic factor for AL onset (OR: 2.63; p = 0.03). No difference was noted between the two groups in terms of AS and AH. CONCLUSION: Three-row CSs significantly decrease the rate of AL after rectal resection. Further multicenter controlled trials are still needed to confirm the advantages of three-row CSs on anastomotic complications.

The Role of Surgery in the Management of Gastric Cancer: State of the Art.

Surgery still represents the mainstay of treatment of all stages of gastric cancer (GC). Surgical resections represent potentially curative options in the case of early GC with a low risk of node metastasis. Sentinel lymph node biopsy and indocyanine green fluorescence are novel techniques which may improve the employment of stomach-sparing procedures, ameliorating quality of life without compromising oncological radicality. Nonetheless, the diffusion of these techniques is limited in Western countries. Conversely, radical gastrectomy with extensive lymphadenectomy and multimodal treatment represents a valid option in the case of advanced GC. Differences between Eastern and Western recommendations still exist, and the optimal multimodal strategy is still a matter of investigation. Recent chemotherapy protocols have made surgery available for patients with oligometastatic disease. In this context, intraperitoneal administration of chemotherapy via HIPEC or PIPAC has emerged as an alternative weapon for patients with peritoneal carcinomatosis. In conclusion, the surgical management of GC is still evolving together with the multimodal strategy. It is mandatory for surgeons to be conscious of the current evolution of the surgical management of GC in the era of multidisciplinary and tailored medicine.

When to Perform a Colonoscopy in Diverticular Disease and Why: A Personalized Approach.

Colonoscopy is a crucial diagnostic tool in managing diverticular disease (DD). Diverticulosis can often be an unexpected diagnosis when colonoscopy is performed in asymptomatic subjects, generally for colorectal cancer screening, or it could reveal an endoscopic picture compatible with DD, including acute diverticulitis, in patients suffering from abdominal pain or rectal bleeding. However, alongside its role in the differential diagnosis of colonic diseases, particularly with colon cancer after an episode of acute diverticulitis or segmental colitis associated with diverticulosis, the most promising use of colonoscopy in patients with DD is represented by its prognostic role when the DICA (Diverticular Inflammation and Complication Assessment) classification is applied. Finally, colonoscopy plays a crucial role in managing diverticular bleeding, and it could sometimes be used to resolve other complications, particularly as a bridge to surgery. This article aims to summarize "when" to safely perform a colonoscopy in the different DD settings and "why".

Artificial Intelligence in Colorectal Cancer Surgery: Present and Future Perspectives.

Artificial intelligence (AI) and computer vision (CV) are beginning to impact medicine. While evidence on the clinical value of AI-based solutions for the screening and staging of colorectal cancer (CRC) is mounting, CV and AI applications to enhance the surgical treatment of CRC are still in their early stage. This manuscript introduces key AI concepts to a surgical audience, illustrates fundamental steps to develop CV for surgical applications, and provides a comprehensive overview on the state-of-the-art of AI applications for the treatment of CRC. Notably, studies show that AI can be trained to automatically recognize surgical phases and actions with high accuracy even in complex colorectal procedures such as transanal total mesorectal excision (TaTME). In addition, AI models were trained to interpret fluorescent signals and recognize correct dissection planes during total mesorectal excision (TME), suggesting CV as a potentially valuable tool for intraoperative decision-making and guidance. Finally, AI could have a role in surgical training, providing automatic surgical skills assessment in the operating room. While promising, these proofs of concept require further development, validation in multi-institutional data, and clinical studies to confirm AI as a valuable tool to enhance CRC treatment.

Development and Validation of Predictive Assessment of Complicated Diverticulitis Score.

The prevalence of acute diverticulitis (AD) has progressively increased in recent decades, with correspondingly greater morbidity and mortality. The aim of the study is to develop a predictive score to identify patients with the highest risk of complicated AD. The clinical records of 1089 patients referred to the emergency department (ED) over a five-year period were reviewed. In multivariate analysis, male sex (p < 0.001), constipation (p = 0.002), hemoglobin < 11.9 g/dL (p < 0.001), C reactive protein > 80 mg/L (p < 0.001), severe obesity (p = 0.049), and no proton pump inhibitor treatment (p = 0.003) were independently associated with complicated AD. The predictive assessment of complicated (PACO)-diverticulitis (D) score, including these six variables, was applied to the retrospective cohort and then validated prospectively in a cohort including 282 patients. It categorized patients into three risk classes for complicated AD. The PACO-D score showed fair discrimination for complicated AD with an area under the receiver operating characteristic curve of 0.674 and 0.648, in the retrospective and prospective cohorts, respectively. The PACO-D score could be a practical clinical tool to identify patients at highest risk for complicated AD referred to the ED so that appropriate diagnostic and therapeutic resources could be appropriately allocated. Further external validation is needed to confirm these results.

Covid-19 and the management of patients with inflammatory bowel disease: a practical decalogue for the post-pandemic phase.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised several concerns for patients with chronic immune-mediated diseases, including inflammatory bowel disease (IBD). As the outbreak appears to be in the descending phase, at least in some part of the world, as in most European countries, guidance is urgently needed to provide optimal care for our IBD patients in order to gradually and safely reduce the gap in care that has been accumulated in the months of lockdown and to face all the backlogs. Therefore, we have provided a decalogue of practical recommendations for gastroenterologists to manage patients with IBD in the post-peak phase of the COVID-19 pandemic. They include all the aspects of IBD care, not only pharmacological ones but also endoscopy, surgery, psychological treatment, telemedicine, diagnostics and educational tasks provided by doctors and patient associations.

A modern multidisciplinary approach to the treatment of enterocutaneous fistulas in Crohn's disease patients.

INTRODUCTION: Enterocutaneous fistulas (ECFs) is a manifestation of penetrating Crohn's disease (CD) that is challenging to treat and has considerable morbidity and mortality rates. AREAS COVERED: This review aims to explore the practical and updated principles for the optimal treatment of ECFs in CD patients. EXPERT OPINION: Optimal ECF management requires a multidisciplinary approach. Treatment first includes fluid resuscitation and electrolyte rebalancing with control of sepsis by means of antibiotics and, when indicated, drainage of infected collections. Subsequent therapeutic steps include nutritional support, control of the fistula output and treatment of peristomal skin. Anti-TNF-α therapy seems to have limited utility only after sepsis is resolved and intestinal stenosis excluded. However, ECFs heal in only approximately one-third of cases without surgical intervention. Thus, correct surgical timing combined with adequate nutritional support, sepsis resolution and skin care is considered the appropriate preoperative setting.

Venous Thromboembolism in Patients with Inflammatory Bowel Disease: The Role of Pharmacological Therapy and Surgery.

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE). Alongside the traditional acquired and genetic risk factors for VTE, patients with IBD have pathogenic and clinical peculiarities that are responsible for the increased number of thromboembolic events occurring during their life. A relevant role in modifying this risk in a pro or antithrombotic manner is played by pharmacological therapies and surgery. The availability of several biological agents and small-molecule drugs with different mechanisms of action allows us to also tailor the treatment based on the individual prothrombotic risk to reduce the occurrence of VTE. Available review articles did not provide sufficient and updated knowledge on this topic. Therefore, we assessed the role of each single treatment, including surgery, in modifying the risk of VTE in patients with IBD to provide physicians with recommendations to minimize VTE occurrence. We found that the use of steroids, particularly if prolonged, increased VTE risk, whereas the use of infliximab seemed to reduce such risk. The data relating to the hypothesized prothrombotic risk of tofacitinib were insufficient to draw definitive conclusions. Moreover, surgery has an increased prothrombotic risk. Therefore, implementing measures to prevent VTE, not only with pharmacological prophylaxis but also by reducing patient- and surgery-specific risk factors, is necessary. Our findings confirm the importance of the knowledge of the effect of each single drug or surgery on the overall VTE risk in patients with IBD, even if further data, particularly regarding newer drugs, are needed.

Human herpesvirus 8-associated colonic Kaposi's sarcoma during vedolizumab treatment in ulcerative colitis: a case report and review of the literature.

BACKGROUND: Kaposi's sarcoma (KS) is a rare vascular tumor associated with human herpesvirus (HHV)-8 infection. One of the variants of KS is defined iatrogenic and is overall reported in transplanted patient but also, although less frequently, in patients treated with long-standing immunosuppressive therapy, such as in inflammatory bowel disease including ulcerative colitis and Crohn's disease. CASE PRESENTATION: Herein, we report the first case of KS in a human immunodeficiency virus (HIV)-negative 47-year old male with UC after treatment with the α4-ß7 integrin inhibitor vedolizumab (VDZ). The patient underwent to colectomy for a medical refractory disease and the histological examination of the surgical specimen showed the typical findings of KS together with the HHV-8 positivity. The patient achieved a good health status, without any sign of disease recurrence. CONCLUSIONS: In the present case, we can assume that VDZ may have promoted the reactivation of a latent HHV-8 infection endowed with oncogenic potentialities and, in turn, the onset of KS. We also briefly reviewed all the cases of KS in HIV-negative patients with inflammatory bowel disease.

Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies.

BACKGROUND: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. METHODS AND FINDINGS: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). INTERPRETATION: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. FUND: This work was financially supported by grants from "Ministero della Salute Italiano"(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from "Associazione Italiana Cancro" (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

Course of the Diverticular Disease: What is changing?

In this session several critical issues in diverticular disease were considered, including "It is Symptomatic Diverticular Disease or Irritable Bowel Syndrome?", "What do determine evolution to diverticulitis, bowel habits alteration or inflammation?", and "Prevention of acute diverticulitis: Is it at all possible?". The first talking compared symptoms and laboratory findings between Symptomatic Uncomplicated Diverticular Disease  (SUDD) and Irritable Bowel Syndrome (IBS). Although both disease share some symptoms, and although IBS can occur in patients having diverticulosis,  SUDD and IBS can be differentiate using a combination of symptoms and laboratory tools. The second talking debated what are the most important risk factors for the evolution towards acute diverticulitis. Current data seem to exclude a significant role of bowel habits alteration, while inflammation seems to have a stronger role, especially in causing acute diverticulitis recurrence. The third talking analyzed about the acute diverticulitis prevention. Primary prevention seem to be little better when using mesalazine, while no definite conclusion can be drawn about the use of fiber and rifaximin. About the secondary prevention, no drugs can be currently advised due to lacking of definite results. At the same time, surgery should be advised on case-by-case basis.

Can We Predict the Efficacy of Anti-TNF-α Agents?

The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNF-α therapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

The Economic Burden of Diverticular Disease.

Diverticular disease (DD) of the colon represents a common clinical condition affecting from one-fourth to one-third of the population in developed countries. Several epidemiological studies have clearly shown that in the last decades the rates of clinic visits and hospital admissions for DD and its complications are progressively increased. In addition, complications of DD are associated to a high mortality rate that continues unabated despite advances in surgery and intensive care. As consequence, the burden on health care resources has significantly increased over time, leading DD among the main causes of health spending for gastrointestinal diseases. In this review the most important data regarding health care resources utilization and costs for DD are analyzed and some proposals for reducing the burden on health care systems are hypothesized.