Publications by authors named "Gianluca Sampietro"

61 Publications

Poorly Cohesive Carcinoma of the Nonampullary Small Intestine: A Distinct Histologic Subtype With Prognostic Significance.

Am J Surg Pathol 2021 Oct 11. Epub 2021 Oct 11.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia Anatomic Pathology, Fondazione IRCCS San Matteo Hospital Clinical Epidemiology & Biometry Unit, Fondazione IRCCS San Matteo Hospital Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, Pavia Pathology Unit, Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua Veneto Institute of Oncology, IOV-IRCCS, Padua Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese Gatroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital Department of Biochemical and Clinical Sciences, University of Milan, Milan Division of General and HPB Surgery, ASST Rhodense, Rho Gatroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for >50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixed-poorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of <10% of signet-ring cells, and all but 1 SB-PCCs exhibited loss of membranous expression of E-cadherin. Compared with SBAs-NOS, SB-PCCs showed a significantly younger patient age at diagnosis, and a stronger association with Crohn disease, and both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs featured a higher rate of lymphovascular and perineural invasion and a lower percentage of mismatch repair-deficient cases. Importantly, the cancer-specific survival of SB-PCC (hazard ratio: 3.81; 95% confidence interval: 1.90-7.64; P<0.001) and mixed-poorly-cohesive-glandular-SBA (4.12; 2.20-7.71; P<0.001) patients was significantly worse compared with SBAs-NOS cases. This study provides objective evidence to the World Health Organization (WHO) 2019 introduction of SB-PCC as a distinctive subtype of nonampullary SBA, by virtue of its unique clinical and histologic features, and suggests that both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs should be separated from SBAs-NOS.
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http://dx.doi.org/10.1097/PAS.0000000000001821DOI Listing
October 2021

Circulating Fibroblast Activation Protein as Potential Biomarker in Patients With Inflammatory Bowel Disease.

Front Med (Lausanne) 2021 21;8:725726. Epub 2021 Sep 21.

Nanomedicine and Molecular Imaging Lab, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

A major concern in the management of Inflammatory Bowel Disease (IBD) is the absence of accurate and specific biomarkers to drive diagnosis and monitor disease status timely and non-invasively. Fibroblast activation protein (FAP) represents a hallmark of IBD bowel strictures, being overexpressed in stenotic intestinal myofibroblasts. The present study aimed at evaluating the potential of circulating FAP (cFAP) as an accessible blood biomarker of IBD. Quantitative determination of cFAP was performed by enzyme-linked immunosorbent assay on plasma samples prospectively collected from patients with IBD and control subjects. A discrimination model was established on a training set of 50% patients and validated on independent samples. Results showed that cFAP concentration was reduced in patients with IBD when compared to controls ( < 0.0001). Age, sex, smoking, disease location and behavior, disease duration and therapy were not associated with cFAP. The sensitivity and specificity of cFAP in discriminating IBD from controls were 70 and 84%, respectively, based on the optimal cutoff (57.6 ng mL, AUC = 0.78). Predictions on the test set had 57% sensitivity, 65% specificity, and 61% accuracy. There was no strong correlation between cFAP and routine inflammatory markers in the patients' population. A subgroup analysis was performed on patients with Crohn's disease undergoing surgery and revealed that cFAP correlates with endoscopic mucosal healing. In conclusion, cFAP deserves attention as a promising blood biomarker to triage patients with suspected IBD. Moreover, it might function as a biomarker of post-operative remission in patients with Crohn's disease.
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http://dx.doi.org/10.3389/fmed.2021.725726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490650PMC
September 2021

Acute severe ulcerative colitis: How to reduce operating time under 150 min for emergency laparoscopic colectomy - A video vignette.

Colorectal Dis 2021 Sep 29. Epub 2021 Sep 29.

Division of Surgery, ASST Rhodense, Rho Memorial Hospital, Milano, Italy.

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http://dx.doi.org/10.1111/codi.15928DOI Listing
September 2021

Prevalence and significance of mesentery thickening and lymph nodes enlargement in Crohn's disease.

Dig Liver Dis 2021 Jul 19. Epub 2021 Jul 19.

Department of Biomedical and Clinical Science "Luigi Sacco", University of Milan, Italy.

Background: Mesentery thickening and enlarged lymphnodes are typical findings of Crohn's disease (CD), but their role is unknown. Aim of the present study was to evaluate their prevalence and significance on postoperative complications and long-term surgical recurrence after CD surgery.

Methods: 1272 consecutive, unselected patients were retrospectively reviewed, divided into 4 groups based on the presence or absence of a thickened mesentery and enlarged lymphnodes, and stratified for primary or recurrent surgical procedure. In all patients but those treated with strictureplasty the mesentery and lymphnodes were removed. Patients' characteristics, peri-operative findings, and long-term recurrence were compared by univariate and multivariate analysis.

Results: Thickened mesentery and enlarged lymphnodes were not present in all cases, were typical of ileal location and penetrating behaviour, had a constant decrease over recurrences, were independent of either pre-operative medical therapy or surgical approach, did not increase the duration of surgery and complications, presented similar 20-years recurrence rate to normal mesentery and lymphnodes. Lymphopathy was associated to a worst nutritional status during disease recurrences. At multivariate analysis, age, location, and behaviour, but not mesenteric characteristics, were related to an increased risk of surgical recurrence.

Conclusions: This study provides new information on mesentery and lymphnodes in CD patients. Further studies are needed to clarify the appropriate surgical approach.
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http://dx.doi.org/10.1016/j.dld.2021.06.030DOI Listing
July 2021

Inflammatory Bowel Disease patients requiring surgery can be treated in referral centres regardless of the COVID-19 status of the hospital: results of a multicentric European study during the first COVID-19 outbreak (COVIBD-Surg).

Updates Surg 2021 Oct 26;73(5):1811-1818. Epub 2021 Jun 26.

Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Outcomes of inflammatory bowel disease (IBD) patients requiring surgery during the outbreak of Coronavirus disease 19 (COVID-19) are unknown. Aim of this study was to analyse the outcomes depending on the COVID-19 status of the centre. Patients undergoing surgery in six COVID-19 treatment and one COVID-free hospitals (five countries) during the first COVID-19 peak were included. Variables associated with risk of moderate-to-severe complications were identified using logistic regression analysis. A total of 91 patients with Crohn's disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in one of the COVID-19-treatment hospitals, while 25 (27.5%) in the COVID-19-free centre. More COVID-19-treatment patients required urgent surgery (48.4% vs. 24%, p = 0.035), did not discontinue biologic therapy (15.1% vs. 0%, p = 0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p = 0.0033), and required intensive care admission (10.6% vs. 0%, p = 0.032). Three patients (4.6%) had a SARS-CoV-2 infection postoperatively. Postoperative complications were associated with the use of steroids at surgery (Odds ratio [OR] = 4.10, 95% CI 1.14-15.3, p = 0.03), presence of comorbidities (OR = 3.33, 95% CI 1.08-11, p = 0.035), and Crohn's disease (vs. ulcerative colitis, OR = 3.82, 95% CI 1.14-15.4, p = 0.028). IBD patients can undergo surgery regardless of the COVID-19 status of the referral centre. The risk of SARS-CoV-2 infection should be taken into account.
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http://dx.doi.org/10.1007/s13304-021-01119-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235901PMC
October 2021

Laparoscopy and survival in colon cancer: A further step beyond the non-inferiority?

Dig Liver Dis 2021 Aug 8;53(8):935-936. Epub 2021 Jun 8.

Division of General and HPB Surgery, ASST Rhodense, Rho, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2021.05.008DOI Listing
August 2021

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn's disease-associated small bowel carcinoma.

Virchows Arch 2021 Oct 8;479(4):667-678. Epub 2021 May 8.

Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Via Carlo Forlanini 16 -, 27100, Pavia, Italy.

Most Crohn's disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.
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http://dx.doi.org/10.1007/s00428-021-03109-2DOI Listing
October 2021

Strictureplasties performed by laparoscopic approach for complicated Crohn's disease. A prospective, observational, cohort study.

Dig Liver Dis 2021 Oct 21;53(10):1286-1293. Epub 2021 Feb 21.

Department of Biomedical and Clinical Science "Luigi Sacco", University of Milan, Italy.

Background: Laparoscopy is considered the best surgical approach for Crohn's Disease (CD), and strictureplasty a reliable alternative to intestinal resection. Nevertheless, their association has never been evaluated.

Aim: To investigate feasibility and safety of conventional (SP) and non-conventional (NCSP) strictureplasties, using laparoscopy, for complicated CD.

Methods: Starting January 2008, a prospective cohort study was performed, in consecutive, unselected patients, undergoing primary surgery for CD (Group-A). The residential database (CD-CARD) was used for the retrospective extraction of control patients (Group-B). Univariate and multi-variate analysis of pre-operative characteristics, intra-operative findings, morbidity, and intra-abdominal septic complications (IASCs) was performed.

Results: Between January 2008 and December 2019, 331 patients received 162 SPs, 138 NCSPs, and 373 resections (Group-A). From the CD-CARD, 227 control patients received 159 SPs, 117 NCSPs, and 271 resections (Group-B) (ns). Preoperatively, Group-A presented batter nutritional status and received more biological therapies, Group-B more steroids. Group-A presented less abdominal abscesses, planned ostomies, minor complications, shorter operating time and hospitalization than Group-B, but similar major complications, IASCs and anastomotic leaks. IASCs were related to older age, elevated inflammatory indices, and preoperative treatment with high-risk drugs.

Conclusions: SP and NCSP are feasible by laparoscopy, with low morbidity rate, confirming the advantages of both minimally invasive and conservative surgery.
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http://dx.doi.org/10.1016/j.dld.2021.01.023DOI Listing
October 2021

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study.

Updates Surg 2021 Feb 6;73(1):149-156. Epub 2021 Jan 6.

Department of Advanced Medical and Surgical Science, Universita' degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD.
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http://dx.doi.org/10.1007/s13304-020-00918-zDOI Listing
February 2021

Single-incision laparoscopic surgery (SILS) for the treatment of ileocolonic Crohn's disease: a propensity score-matched analysis.

Int J Colorectal Dis 2021 Mar 23;36(3):605-608. Epub 2020 Dec 23.

Department of Advanced Medical and Surgical Sciences, Universita' degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Introduction: Single-incision laparoscopic surgery (SILS) aims to minimize the surgical access trauma by reducing the number of abdominal incisions to a single site, potentially offering better cosmetic results and decreased postoperative pain. In this study, we compare the results of SILS ileocolic resection for Crohn's disease (CD) to conventional laparoscopy and open surgery using a propensity score-matched analysis in a retrospective national multicentre study.

Methods: All consecutive patients undergoing elective SILS ileocaecal or redo ileocolic resection for primary and recurrent CD from 1 June 2018 to 31 May 2019 were included. Patients were matched 1:1:1 with laparoscopy and open surgery according to perianal disease, recurrent disease, penetrating phenotype of CD, history of previous abdominal surgery, preoperative medical treatment with steroids and anti-TNF. Postoperative morbidity within 30 days of surgery was the primary endpoint.

Results: Fifty-eight patients were included in each group, for a total of 174 patients. The conversion rate for SILS and laparoscopy was 10.3% and 12%, respectively, with no difference in the incidence of postoperative complications (13.8% and 12%, p = 0.77), whilst open surgery demonstrated a worse morbidity profile, with a complication rate of 25.9% (p < 0.0001). Median length of hospital stay following SILS ileocolic resection was 5 days, significantly shorter compared to 7 days for laparoscopy and 9 for open surgery (p < 0.0001).

Conclusions: SILS ileocolonic resection for CD demonstrated a comparable morbidity profile compared to laparoscopy in selected patients, with a reduced length of postoperative hospital stay.
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http://dx.doi.org/10.1007/s00384-020-03821-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895768PMC
March 2021

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall.

Cancers (Basel) 2020 Nov 19;12(11). Epub 2020 Nov 19.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy.

Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers ( = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.
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http://dx.doi.org/10.3390/cancers12113441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699330PMC
November 2020

Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease.

Int J Nanomedicine 2020 2;15:8537-8552. Epub 2020 Nov 2.

Department of Biomedical and Clinical Sciences "Luigi Sacco, Università degli studi di Milano, Milano, 20157, Italy.

Purpose: Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci.

Materials And Methods: We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots ([email protected] NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model.

Results: Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, [email protected] NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to [email protected] NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice.

Conclusion: [email protected] NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.
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http://dx.doi.org/10.2147/IJN.S264513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646444PMC
December 2020

Sequential Approach for a Critical-View COlectomy (SACCO): A Laparoscopic Technique to Reduce Operative Time and Complications in IBD Acute Severe Colitis.

J Clin Med 2020 Oct 21;9(10). Epub 2020 Oct 21.

Department of Biomedical and Clinical Sciences, University of Milano, 20157 Milano, Italy.

Acute severe colitis is the major indication for surgery in inflammatory bowel diseases (IBD), and in particular, in ulcerative colitis (UC). A laparoscopic approach for abdominal colectomy is recommended, due to better perioperative and long-term outcomes. However, costs, time-spending, and outcomes are still a topic of improvement. We designed a standardized 10-steps, sequential approach to laparoscopic colectomy, based on the philosophy of the "critical view of safety", with the aim to improve perioperative outcomes (operative duration, estimated blood loss, complications, readmissions, reoperations, and length of postoperative stay). We performed a retrospective cohort study using data from a prospectively maintained clinical database. We included all the consecutive, unselected patients undergoing laparoscopic subtotal colectomy (SCo) for IBD between 2008 and 2019 in a tertiary IBD Italian Centre. Starting from 2015, we regularly adopted the novel Sequential Approach for a Critical-View Colectomy (SACCo) technique. We included 59 (40.6%) patients treated with different laparoscopic approaches, and 86 patients (59.4%) operated on by the SACCo procedure. The mean operating time was significantly shorter for the SACCo group (144 vs. 224 min; < 0.0001). The SACCo technique presented a trend to fewer major complications (6.8% vs. 8.3%), less readmissions (2.3% vs. 13.5%; = 0.01), and shorter postoperative hospital stay (7.2 vs. 8.8 days; = 0.003). Laparoscopic SACCo-technique is a safe and reproducible surgical approach for acute severe colitis and may improve the outcomes of this demanding procedure.
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http://dx.doi.org/10.3390/jcm9103382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589891PMC
October 2020

Modified Kudo classification can improve accuracy of virtual chromoendoscopy with FICE in endoscopic surveillance of ulcerative colitis.

Endosc Int Open 2020 Oct 22;8(10):E1414-E1422. Epub 2020 Sep 22.

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Milan, Italy.

 Virtual chromoendoscopy with Fuji Intelligent Color Enhancement (FICE) has never been studied in prospective trials of endoscopic surveillance for ulcerative colitis (UC). We compared FICE and white light endoscopy (WLE) in differentiation of visible lesions in UC.  In a prospective parallel study, we compared consecutive outpatients with UC submitted to surveillance colonoscopy with FICE or WLE. At least one visible polypoid or non-polypoid lesion for each patient was required. Random biopsies from normal mucosa, targeted biopsies or removal of suspected neoplastic lesions and targeted biopsies of unsuspected lesions were performed. In the FICE arm, neoplasia was suspected according to a modified Kudo classification (FICE-KUDO/inflammatory bowel disease [IBD]). Sensitivity (SE), specificity (SP), positive and negative likelihood ratios (LR) and negative predictive value (NPV) were analyzed.  One hundred patients were submitted to FICE (n = 46) or WLE (n = 54). Twenty-two patients (11 in WLE, 11 in FICE) had a least one neoplastic lesion. No neoplasia was found in random biopsies. Among 275 lesions, 17 of 136 by FICE and 27 of 139 by WLE were suspected neoplasia, but 28 (14 in each arm) were true neoplastic lesions. The accuracy of FICE-KUDO/IBD vs WLE (per lesion) was: SE 93 % vs 64 % (  = 0.065), SP 97 % vs 86 % (  = 0.002), positive-LR 28.3 vs 4.5 (  = 0.001), negative-LR 0.07 vs 0.42 (  = 0.092), NPV 99 % vs 96 % (  = 0.083). FICE-KUDO/IBD detected more non-polypoid lesions than WLE (  = 0.016).  Targeted biopsies of polypoid and non-polypoid lesions, using the modified Kudo classification with FICE are more accurate than WLE in UC surveillance.
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http://dx.doi.org/10.1055/a-1165-0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508663PMC
October 2020

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

Ann Surg Oncol 2021 Feb 5;28(2):1167-1177. Epub 2020 Aug 5.

Unit of Pathology, Cervello Hospital, Palermo, Italy.

Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer.

Patients And Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability.

Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status.

Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.
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http://dx.doi.org/10.1245/s10434-020-08926-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801310PMC
February 2021

Impact of COVID-19 Outbreak on the Management of Patients With Severe IBD: A Domino Effect.

Gastroenterology 2021 05 12;160(6):2196-2197. Epub 2020 May 12.

Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1053/j.gastro.2020.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214299PMC
May 2021

Raman Analysis Reveals Biochemical Differences in Plasma of Crohn's Disease Patients.

J Crohns Colitis 2020 Nov;14(11):1572-1580

Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

Backgrounds And Aims: There is no accurate and reliable circulating biomarker to diagnose Crohn's disease [CD]. Raman spectroscopy is a relatively new approach that provides information on the biochemical composition of samples in minutes and virtually without any sample preparation. We aimed to test the use of Raman spectroscopy analysis of plasma samples as a potential diagnostic tool for CD.

Methods: We analysed by Raman spectroscopy dry plasma samples obtained from 77 CD patients [CD] and 45 healthy controls [HC]. In the dataset obtained, we analysed spectra differences between CD and HC, as well as among CD patients with different disease behaviours. We also developed a method, based on principal component analysis followed by a linear discrimination analysis [PCA-LDA], for the automatic classification of individuals based on plasma spectra analysis.

Results: Compared with HC, the CD spectra were characterised by less intense peaks corresponding to carotenoids [p <10-4] and by more intense peaks corresponding to proteins with β-sheet secondary structure [p <10-4]. Differences were also found on Raman peaks relative to lipids [p = 0.0007] and aromatic amino acids [p <10-4]. The predictive model we developed was able to classify CD and HC subjects with 83.6% accuracy [sensitivity 80.0% and specificity 85.7%] and F1-score of 86.8%.

Conclusions: Our results indicate that Raman spectroscopy of blood plasma can identify metabolic variations associated with CD and it could be a rapid pre-screening tool to use before further specific evaluation.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa080DOI Listing
November 2020

Management of Rectal Stump During Laparoscopic Subtotal Colectomy for Inflammatory Bowel Disease: A Comparative Cohort Study from Six Referral Centres.

J Crohns Colitis 2020 Sep;14(9):1214-1221

Department of Colorectal Surgery, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris VII, Clichy, France.

Background And Aims: There is no consensus on the best management of the rectum after subtotal colectomy for refractory colitis complicating inflammatory bowel disease [IBD]. The objective was to evaluate the impact of rectal stump management during laparoscopic subtotal colectomy [LSTC] for IBD.

Methods: Patients who underwent LSTC with double-end ileo-sigmoidostomy [Gr.A] or end ileostomy with closed rectal stump [Gr.B] for IBD were included from a retrospective database of six European referral centres.

Results: In total, 314 patients underwent LSTC and were allocated to Gr.A [n = 102] and B [n = 212]. After LSTC, stoma-related complications occurred more frequently in Gr.A [12%] than in Gr.B [4%, p = 0.01]. Completion proctectomy with ileal pouch-anal anastomosis [IPAA] was performed as a three-stage procedure in all patients from Gr.A, and in 88 patients from Gr.B [42%; Gr.B1]. The other 124 patients from Gr.B underwent a modified two-stage procedure [58%; Gr.B2]. The second stage was performed laparoscopically in all patients from Gr.A compared with 73% of Gr.B1 [p < 0.0001] and 65% of Gr.B2 patients [p < 0.0001]. When laparoscopy was intended for 2nd stage IPAA, conversion to laparotomy occurred less frequently in Gr.A when compared with B1 [0 vs 5%, p = 0.06] or B2 [10%, p = 0.001]. When all surgical stages were included [LSCT and IPAA], cumulative stoma-related complications occurred more frequently in Gr.A [n = 19] than in Gr.B1 [n = 6, p = 0.02] and Gr.B2 [n = 6, p = 0.001].

Conclusion: This study suggests that both techniques of double-end ileosigmoidostomy and end ileostomy with closed rectal stump are safe and effective for rectal stump management after laparoscopic subtotal colectomy.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa046DOI Listing
September 2020

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Mod Pathol 2020 07 17;33(7):1398-1409. Epub 2020 Feb 17.

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
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http://dx.doi.org/10.1038/s41379-020-0497-0DOI Listing
July 2020

Torsion of wandering spleen involving the pancreatic tail.

Ann Med Surg (Lond) 2020 Feb 20;50:10-13. Epub 2019 Dec 20.

Department of Biomedical and Clinical Sciences, L. Sacco Hospital University of Milan, Italy.

Background: Wandering spleen (WS) is a rare clinical entity resulting from the absence or maldevelopment of the ligaments normally involved in the attachment of the spleen in its normal position. WS can be a cause of acute abdomen leading to different complications ranging from torsion of the vascular pedicle to spleen infarction. Often, in absence of symptoms, it is an occasional finding during radiological exams and surgery represents the gold standard in the management of this unusual condition.

Case Presentation: We present a case of wandering spleen in a young nulliparous female with an history of recurrent abdominal pain. A preoperative CT-scan of the abdomen showed the presence of a multi-infarcted spleen twisted several times around its vascular pedicle, involving the tail of pancreas. The patient was electively treated with laparoscopic splenectomy.

Conclusions: A laparoscopic approach is feasible in the treatment of this pathology. A correct and timely diagnosis of this condition is crucial to allow an organ preserving surgery. There are only few reported cases in literature describing an involvement of the tail of the pancreas in the torsion of the vascular pedicle. Complete excision of the ectasic veins tributaries of the splenic vein avoids the risk of postoperative vein thrombosis and bleeding.
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http://dx.doi.org/10.1016/j.amsu.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994766PMC
February 2020

Risk factors for locally advanced cancer associated with ulcerative colitis: Results of a retrospective multicentric study in the era of biologics.

Dig Liver Dis 2020 01 30;52(1):33-37. Epub 2019 Sep 30.

Surgery of the Alimentary Tract, Sant'Orsola Hospital, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Background: Patients affected by ulcerative colitis (UC) are more likely to develop colorectal cancer, and are often diagnosed with lymph node involvement (N+) at surgery.

Aim: To identify the risk factors for N+ cancer in UC patients.

Methods: Patients undergoing surgery from 2001 to 2018 in six European tertiary centres were included. N+ patients were compared to the control group (N-) for clinical variables. The evaluation of risk factors for N+ was assessed using univariate and multivariable logistic regression analyses.

Results: A total of 130 patients were included. Median duration of disease was 21 years (1-52). Forty patients (30.8%) were N+ at surgery. Eighteen (13.8%) developed cancer within 10 years from the onset of UC. Younger age at surgery (Odds ratio -OR- 0.96, p = 0.042), left colon location (OR 2.44, p = 0.045) and the presence of stricture (OR 5.07, p = 0.002) were associated with N+.

Conclusion: Location in the left colon, presence of strictures and younger age strongly correlated with a higher risk of N+ cancer, which could develop before the starting point of surveillance. Duration, extension and severity of disease were not associated with N+. These results should be considered in the evaluation of risk of advanced cancer in UC patients.
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http://dx.doi.org/10.1016/j.dld.2019.08.024DOI Listing
January 2020

Separation of Low- Versus High-grade Crohn's Disease-associated Small Bowel Carcinomas is Improved by Invasive Front Prognostic Marker Analysis.

J Crohns Colitis 2020 Mar;14(3):295-302

IBD, San Filippo Neri Hospital, Rome, Italy.

Background And Aims: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis.

Methods: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium.

Results: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months.

Conclusions: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.
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http://dx.doi.org/10.1093/ecco-jcc/jjz140DOI Listing
March 2020

Minimally invasive surgery and stoma-related complications after restorative proctocolectomy for ulcerative colitis. A two-centre comparison with open approach.

Am J Surg 2019 04 24;217(4):682-688. Epub 2018 Jul 24.

Luigi Sacco University Hospital, Department of Oncology, Gastroenterology and Surgery-University of Milan, Italy.

Background: Although the creation of a stoma reduces the risk of septic pouch complications following ileal pouch-anal anastomosis (IPAA), the stoma itself and its reversal can give rise to substantial morbidity during the two- or three-stage concept. Aim of study is to compare stoma-related complications in Ulcerative Colitis patients undergoing laparoscopic versus open IPAA.

Methods: We collected data on 250 IPAA patients from two Italian Centres between 2005 and 2015. We compared perioperative and postoperative events in 150 open vs 100 laparoscopic IPAA. We performed a case-matched analysis based on baseline differences among groups to compare the rate of mechanical complications.

Results: There were no significant differences between open and laparoscopic IPAA in overall stoma complications (complications during ileostomy: 11.3% vs 12%,p = 0.8; early complications: 10% vs 8%,p = 0.5; late complications: 12.6% vs 6%,p = 0.08). The case-matched analysis found a slightly reduced incidence of obstructive complications at any stage with laparoscopy.

Conclusions: Overall stoma related complications do not seem to be reduced by minimally-invasive approach itself, but patients might experience less mechanical problems with laparoscopy without conversion.
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http://dx.doi.org/10.1016/j.amjsurg.2018.07.028DOI Listing
April 2019

Totally laparoscopic, multi-stage, restorative proctocolectomy for inflammatory bowel diseases. A prospective study on safety, efficacy and long-term results.

Dig Liver Dis 2018 12 21;50(12):1283-1291. Epub 2018 May 21.

Division of General Surgery, ASST Fatebenefratelli - Sacco, Milan, Italy.

Background: Laparoscopic ileo-pouch-anal anastomosis (IPAA) has been reported as having low morbidity and several advantages.

Aims: To evaluate safety, efficacy and long-term results of laparoscopic IPAA, performed in elective or emergency settings, in consecutive unselected IBD patients.

Methods: All the patients received totally laparoscopic 2-stage (proctocolectomy and IPAA - stoma closure) or 3-stage (colectomy - proctectomy and IPAA - stoma closure) procedure according to their presentation.

Results: From July 2007 to July 2016, 160 patients entered the study. 50.6% underwent a 3-stage procedure and 49.4% a 2-stage procedure. Mortality and morbidity were 0.6% and 24.6%. Conversion rate was 3.75%. 8.7% septic complications were associated with steroids and Infliximab treatment (p = 0.0001). 3-stage patients were younger (p = 0.0001), with shorter disease duration (p = 0.0001), minor ASA scores of 2 and 3 (p = 0.0007), lower inflammatory index and better nutritional status (p = 0.003 and 0.0001), fewer Clavien-Dindo's grade II complications (p = .0001), reduced rates of readmission and reoperation at 90 days (p = 0.03), and shorter hospitalization (p = .0001), but with similar pouch and IPAA leakage, compared to 2-stage patients. 8 years pouch failure and definitive ileostomy were 5.1% and 3.7%.

Conclusion: A totally laparoscopic approach is safe and feasible, with very low mortality and morbidity rates and very low conversion rate, even in multi-stage procedures and high-risk patients.
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http://dx.doi.org/10.1016/j.dld.2018.05.009DOI Listing
December 2018

Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy.

Dig Liver Dis 2018 11 28;50(11):1205-1213. Epub 2018 Apr 28.

First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy. Electronic address:

Background: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia.

Aims: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis.

Methods: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants.

Results: A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8.

Conclusion: We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding.
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http://dx.doi.org/10.1016/j.dld.2018.04.021DOI Listing
November 2018

Virtual Chromoendoscopy With FICE for the Classification of Polypoid and Nonpolypoid Raised Lesions in Ulcerative Colitis.

J Clin Gastroenterol 2019 04;53(4):269-276

Gastroenterology Unit.

Goals: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC).

Background: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC.

Study: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored.

Results: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively.

Conclusions: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.
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http://dx.doi.org/10.1097/MCG.0000000000000974DOI Listing
April 2019
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