Publications by authors named "Stefano Merigliano"

63 Publications

Laparoscopic Revisional Surgery After Failed Heller Myotomy for Esophageal Achalasia: Long-Term Outcome at a Single Tertiary Center.

J Gastrointest Surg 2021 Jun 7. Epub 2021 Jun 7.

Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Via Giustiniani, 2, 35128, Padova, Italy.

Background: Laparoscopic Heller myotomy (HM) has gained acceptance as the gold standard of treatment for achalasia. However, 10-20% of the patients will experience symptom recurrence, thus requiring further treatment including pneumodilations (PD) or revisional surgery. The aim of our study was to assess the long-term outcome of laparoscopic redo HM.

Methods: Patients who underwent redo HM at our center between 2000 and 2019 were enrolled. Postoperative outcomes of redo HM patients (redo group) were compared with that of patients who underwent primary laparoscopic HM in the same time span (control group). For the control group, we randomly selected patients matched for age, sex, FU time, Eckardt score (ES), previous PD, and radiological stage. Failure was defined as an Eckardt score > 3 or the need for re-treatment.

Results: Forty-nine patients underwent laparoscopic redo HM after failed primary HM. A new myotomy on the right lateral wall of the EGJ was the procedure of choice in the majority of patients (83.7%). In 36 patients (73.5%) an anti-reflux procedure was deemed necessary. Postoperative outcomes were somewhat less satisfactory, albeit comparable to the control group; the incidence of postoperative GERD was higher in the redo group (p < 0.01). At a median 5-year FU time, a good outcome was obtained in 71.4% of patients in the redo group; further 5 patients (10.2%) obtained a long-term symptom control after complementary PD, thus bringing the overall success rate to 81.6%. Stage IV disease at presentation was independently associated with a poor outcome of revisional LHD (p = 0.003).

Conclusions: This study reports the largest case series of laparoscopic redo HM to date. The procedure, albeit difficult, is safe and effective in relieving symptoms in this group of patients with a highly refractory disease. The failure rate, albeit not significantly, and the post-operative reflux are higher than after primary HM. Patients with stage IV disease are at high risk of esophagectomy.
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http://dx.doi.org/10.1007/s11605-021-05041-xDOI Listing
June 2021

Laparoscopic Heller-Dor Is an Effective Treatment for Esophageal-Gastric Junction Outflow Obstruction.

J Gastrointest Surg 2021 May 6. Epub 2021 May 6.

Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, School of Medicine, Clinica Chirurgica 3, Azienda Ospedale Università di Padova, Padova, Italy.

Background: The treatment of esophagogastric junction outflow obstruction (EGJOO) currently mirrors that of achalasia, but this is based on only a few studies on small case series. The aim of this prospective, controlled study was to assess the outcome of laparoscopic Heller-Dor (LHD) in patients with EGJOO, as compared with patients with esophageal achalasia.

Materials And Methods: Between 2016 and 2019, patients with manometric diagnosis of idiopathic EGJOO and patients with radiological stage I achalasia, both treated with LHD, were compared. The achalasia group was further analyzed by subgrouping the patients based on the manometric pattern. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score > 3 or the need for retreatment.

Results: During the study period, 150 patients were enrolled: 25 patients had EGJOO and 125 had radiological stage I achalasia (25 pattern I, 74 pattern II, and 26 pattern III). The median follow-up was 24 months (IQR: 34-16). Treatment was successful in 96% of patients in the EGJOO group and in 96% of achalasia patients with pattern I, 98.7% in those with pattern II, and 96.2% of those with pattern III (p=0.50). High-resolution manometry showed a reduction in the LES resting pressure and integrated relaxation pressure for all patients in all 4 groups (p<0.001).

Conclusion: This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. LHD emerged as an effective treatment for EGJOO, with an excellent success rate, comparable with the procedure's efficacy in treating early-stage achalasia.
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http://dx.doi.org/10.1007/s11605-021-05021-1DOI Listing
May 2021

Pharyngo-Esophageal Perforation Following Anterior Cervical Spine Surgery: A Single Center Experience and a Systematic Review of the Literature.

Global Spine J 2021 Apr 23:21925682211005737. Epub 2021 Apr 23.

Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Clinica Chirurgica 3°, Via Giustiniani 2, Padova, Italy.

Study Design: Case series and systematic review of the Literature.

Objectives: Pharyngo-esophageal perforation (PEP) is a rare, life-threatening complication of anterior cervical spine surgery (ACSS). Best management of these patients remains poorly defined. The aim of this study is to present our experience with this entity and to perform a systematic Literature review to better clarify the appropriate treatment of these patients.

Methods: Patients referred to our center for PEP following ACSS (January 2002-December 2018) were identified from our database. Moreover, an extensive review of the English Literature was conducted according to the 2009 PRISMA guidelines.

Results: Twelve patients were referred to our Institution for PEP following ACSS. Indications for ACSS were trauma (n = 10), vertebral metastases (n = 1) and disc herniation (n = 1). All patients underwent hardware placement at the time of ACSS. There were 6 early and 6 delayed PEP. Surgical treatment was performed in 11 patients with total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement, anatomical suture of the fistula and suture line reinforcement with myoplasty. Complete resolution of PEP was observed in 6 patients. Five patients experienced PEP persistence, requiring further surgical management in 2 cases. At a median follow-up of 18.8 months, all patients exhibited permanent resolution of the perforation.

Conclusions: PEP following ACSS is a rare but dreadful complication. Partial or total removal of the fixation devices, direct suture of the esophageal defect and coverage with tissue flaps seems to be an effective surgical approach in these patients.
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http://dx.doi.org/10.1177/21925682211005737DOI Listing
April 2021

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

Cancers (Basel) 2021 Feb 7;13(4). Epub 2021 Feb 7.

Department of Surgery, European Institute of Oncology IRCCS, 20141 Milan, Italy.

After the results reported by the "Chemoradiotherapy for esophageal Cancer Followed by Surgery Study" (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively ( ≦ 0.001). Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.
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http://dx.doi.org/10.3390/cancers13040666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915215PMC
February 2021

Foodborne botulism presenting as small bowel obstruction: a case report.

BMC Infect Dis 2021 Jan 12;21(1):55. Epub 2021 Jan 12.

Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, via Giustiniani 2, 35128, Padova, Italy.

Background: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment.

Case Presentation: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution.

Conclusions: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.
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http://dx.doi.org/10.1186/s12879-020-05759-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801865PMC
January 2021

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.

Dis Esophagus 2020 Nov 27. Epub 2020 Nov 27.

General, Esophageal and Gastric Surgery Unit, University Hospital of Verona, Verona, Italy.

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.
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http://dx.doi.org/10.1093/dote/doaa124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717178PMC
November 2020

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

Eur J Haematol 2021 Feb 2;106(2):281-289. Epub 2020 Dec 2.

Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.

Objective: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome.

Methods: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance.

Results: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome.

Conclusion: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.
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http://dx.doi.org/10.1111/ejh.13547DOI Listing
February 2021

Labelled micelles for the delivery of cytotoxic Cu(II) and Ru(III) compounds in the treatment of aggressive orphan cancers: Design and biological in vitro data.

J Inorg Biochem 2020 12 2;213:111259. Epub 2020 Oct 2.

Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy. Electronic address:

A recent study on our metal-dithiocarbamato complexes pointed out the antiproliferative properties and the druglikeness of some new patented derivatives. In this work, the best compounds have been encapsulated in micellar nanocarriers, being also carbohydrate-functionalized on their hydrophilic surface to investigate the possibility of a cancer-selective delivery. In particular, the nonionic block copolymer Pluronic® F127 (PF127) has been chemically modified with sugars and the derivatives characterized by means of NMR spectroscopy and FT-IR spectrophotometry. Then, the two selected complexes (β-[Ru(PipeDTC)]Cl (PipeDTC = piperidine dithiocarbamate) and [Cu(ProOMeDTC)] (ProOMeDTC = L-proline methyl ester dithiocarbamate)), have been loaded into the hydrophobic core of PF127 micelles and cancer-targeting counterparts. These nanoformulations have been studied for their dimensions (DLS, TEM) and stability, and tested for their cytotoxicity against aggressive human cancer cell lines. The in vitro results were paralleled with mechanistic studies through Confocal Laser Scanning Microscopy and xCELLigence analysis.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111259DOI Listing
December 2020

COVID-19 challenge: proactive management of a Tertiary University Hospital in Veneto Region, Italy.

Pathog Glob Health 2020 09 23;114(6):309-317. Epub 2020 Aug 23.

Department of Directional Hospital Management, Azienda Ospedale Università Padova , Padua, Italy.

Background: The aim of this study is to describe the successful emergency plan implemented by Padova University Hospital (AOUP) during the COVID-19 pandemic.

Methods: The emergency plan included early implementation of procedures aimed at meeting the increasing demand for testing and care while ensuring safe and timely care of all patients and guaranteeing the safety of healthcare workers.

Results: From 21 February to 1 May 2020, there were 3,862 confirmed cases of SARS-CoV-2 infection in the Province of Padua. A total of 485 patients were hospitalized in AOUP, of which 91 were admitted to the ICU; 12 .6% of admitted patients died. The average bed occupancy rate in the ICU was 61.1% (IQR 43.6%:77.4%). Inpatient surgery and inpatient admissions were kept for 76% and 74%, respectively, compared to March 2019. A total of 123,077 swabs were performed, 19.3% of which (23,725 swabs) to screen AOUP workers. The screening of all staff showed that 137 of 7,649 (1.8%) hospital workers were positive. No healthcare worker died.

Discussion: AOUP strategy demonstrated effective management of the epidemic thanks to the timely implementation of emergency procedures, a well-coordinated effort shared by all hospital Departments, and their continuous adjustment to the ongoing epidemic. Timely screening of all hospital workers proved to be particularly important to defend the hospital, avoiding epidemic clusters due to unknown positive cases.
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http://dx.doi.org/10.1080/20477724.2020.1806614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480614PMC
September 2020

Endoscopic diode laser therapy for gastric hyperplastic polyps in cirrhotic patients.

Lasers Med Sci 2020 Aug 19. Epub 2020 Aug 19.

Department of Surgery, Oncology and Gastroenterology, Third Surgical Unit, University of Padova, Padua, Italy.

Purpose Endoscopic polypectomy to remove gastric hyperplastic polyps in cirrhotic patients is associated to a high risk of postprocedural bleeding. The current study set out to examine the effect of diode laser therapy used to treat this type of polyps in cirrhotic patients. Methods This single-center study retrospectively examined the data of cirrhotic patients with macroscopic bleeding or anemia who underwent diode laser therapy (940 nm wave length, 30-W power setting in continuous mode) to remove histology-confirmed hyperplastic gastric polyps. Results A total of 222 polyps (mean diameter 10 ± 8 mm) were treated in 55 patients who were included in the study. No complications such as bleeding or perforations were reported. After a mean of 5 ± 4 sessions, 31 patients (56%) were completely healed. In 16 patients (29%), there was only a partial response (mean polyp reduction diameter of 64 ± 15%), while 8 (15%) patients did not respond to treatment. Statistically significant better results were noted in the patients who underwent ≥ 2 laser sessions. Hemoglobin levels and number of blood transfusions required were not statistically different after treatment. After a mean study period of 21 ± 17 months, polyp recurrences were noted in 11 patients (20%), but none of the polyps had degenerated. Conclusion Diode laser therapy was found to be a safe treatment for hyperplastic polyps in cirrhotic patients. Due to the presence of others bleeding lesions in cirrhotic patients, this treatment did not have an impact on anemia and transfusion requirements.
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http://dx.doi.org/10.1007/s10103-020-03127-7DOI Listing
August 2020

Esophageal perforation due to difficult intubation: our experience and review of literature.

Minerva Surg 2021 02 6;76(1):97-98. Epub 2020 Aug 6.

Unit of Endocrine Surgery, Department of Surgery, Istituto Oncologico Veneto (IOV), Padua, Italy.

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http://dx.doi.org/10.23736/S0026-4733.20.08422-9DOI Listing
February 2021

Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.

Nature 2020 08 30;584(7821):425-429. Epub 2020 Jun 30.

School of Medicine, University of Padova, Padua, Italy.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.
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http://dx.doi.org/10.1038/s41586-020-2488-1DOI Listing
August 2020

International guidelines and recommendations for surgery during Covid-19 pandemic: A Systematic Review.

Int J Surg 2020 Jul 23;79:180-188. Epub 2020 May 23.

Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Clinica Chirurgica 3, Via Giustiniani 2, 35128, Padova, Italy.

Background: During the COVID-19 pandemic, surgical departments were forced to re-schedule their activity giving priority to urgent procedures and non-deferrable oncological cases. There is a lack of evidence-based literature providing clinical and organizational guidelines for the management of a general surgery department. Aim of our study was to review the available recommendations published by general Surgery Societies and Health Institutions and evaluate the underlying Literature.

Materials And Methods: A review of the English Literature was conducted according to the AMSTAR and to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results: After eligibility assessment, a total of 22 papers and statements were analyzed. Surgical societies have established criteria for triage and prioritization in order to identify procedures that can be postponed after the pandemic and those that should not. Prioritization among oncologic cases represents a difficult task: clinicians have to balance a possible delay in cancer diagnosis or treatment against the risk for a potential COVID-19 exposure. There is broad agreement among guidelines that indication to proceed with surgery should be discussed in virtual Tumor Boards taking into consideration alternative therapeutic approaches. Several guidelines deal with the role of laparoscopic surgery during the pandemic: a tailored approach is currently suggested, with a case-by-case evaluation provided that appropriate personal protective equipment is available in order to minimize the potential risk of transmission. Finally, there is a considerable agreement in the published Literature concerning the management of the personnel during the peri- and intraoperative phase and on the technical advices regarding the induction, operative and recover maneuvers in COVID-19 cases.

Conclusions: During COVID-19 pandemic, it is of paramount importance to face the emergency in the most effective and efficient manner, retrieving resources from non-essential settings and, at the same time, providing care to high priority non-COVID-19 related diseases.
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http://dx.doi.org/10.1016/j.ijsu.2020.05.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245259PMC
July 2020

An evaluation of trans-anal rectoscopic-assisted minimally invasive surgery (ARAMIS): a new platform for transanal surgery.

Int J Colorectal Dis 2020 Sep 24;35(9):1681-1687. Epub 2020 May 24.

Department of Surgery, Oncology and Gastroenterology, Section of Surgery, University of Padova, Clinica Chirurgica 3^, Sesto Piano Policlinico, Via Giustiniani 2, 35128, Padova, Italy.

Purpose: The study aimed to evaluate the feasibility and safety of a new trans-anal rectoscopic-assisted minimally invasive surgery (ARAMIS) platform to treat rectal lesions.

Methods: ARAMIS was first compared with two transanal minimally invasive surgery platforms (SILS Port and GelPOINT Path) on human cadavers. Surgeons with different experience performed running sutures at different distances, at four quadrants, using the three platforms and gave a score to visibility, safety, and maneuverability. ARAMIS was then utilized on patients affected with rectal neoplasia who met the inclusion criteria. Patients and tumor characteristic and results were prospectively collected. The follow-up examinations included proctoscopy at 3, 6, and 12 months.

Results: According to surgeons' scores, ARAMIS improves visibility and safety with respect to other platforms for distances beyond 10 cm. The procedure, which lasted an average of 59 min, was successfully carried out in 14 patients. No intraoperative or postoperative complications were reported. The mean tumor size was 3 cm; they were located a mean of 11 cm from the anal verge. Complete removal of the lesion was possible in 13/14 patients. There was one case of adenoma recurrence at follow-up.

Conclusion: Study results showed that ARAMIS, which is equipped with an adjustable rectoscope, can be considered a safe, effective platform for transanal surgery. The rectoscope protects the rectum during the procedure, a particularly important consideration when proximal rectal lesions are being treated. Further clinical studies are warranted to confirm these encouraging results.
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http://dx.doi.org/10.1007/s00384-020-03641-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415033PMC
September 2020

Primary mesenteric vein thrombosis: a case series.

J Surg Case Rep 2020 Mar 24;2020(3):rjaa016. Epub 2020 Mar 24.

Department of Surgical, Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy.

Mesenteric vein thrombosis (MVT) is a rare condition, often misdiagnosed due to its vague and misleading clinical presentation. It can cause intestinal infarction, peritonitis, and consequently necessitate bowel resection. CT scanning with intravenous contrast enhancement is the gold standard for its diagnosis. Radiologists have an important role in defining the extent of thrombosis and identifying any signs of intestinal infarction influencing the decision whether or not to operate. In patients with no clinical signs of peritonitis or radiological evidence of intestinal infarction, the treatment can be exclusively medical, based on full anticoagulation (initially with low molecular weight heparin, followed by vitamin K antagonists or direct acting oral-anticoagulants). The duration of medical treatment depends on radiological evidence of resolution of thrombosis and the identification of pro-coagulant risk factors.
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http://dx.doi.org/10.1093/jscr/rjaa016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092682PMC
March 2020

Poem Versus Laparoscopic Heller Myotomy in the Treatment of Esophageal Achalasia: A Case-Control Study from Two High Volume Centers Using the Propensity Score.

J Gastrointest Surg 2020 03 17;24(3):505-515. Epub 2019 Dec 17.

Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Center for Endoscopic Research, Therapeutics and Training (CERTT), Rome, 00168, Italy.

Background: POEM has recently had a widespread diffusion, aiming at being the treatment of choice for esophageal achalasia. The results of ongoing RCTs against laparoscopic myotomy are not available, yet. We, therefore, designed this propensity score (PS) case-control study with the aim of evaluating how POEM compares to the long-standing laparoscopic Heller myotomy + Dor fundoplication (LHD) and verifying if it may really replace the latter as the first-line treatment for achalasia.

Methods: Two groups of consecutive patients undergoing treatment for primary achalasia from January 2014 to November 2017 were recruited in two high-volume centers, one with extensive experience with POEM and one with LHD. Patients with previous endoscopic treatment were included, whereas patients with previous LHD or POEM were excluded. A total of 140 patients in both centers were thus matched. LHD and POEM were performed following established techniques. The patients were followed with clinical (Eckardt score), endoscopic, and pH-manometry evaluations.

Results: The procedure was successfully completed in all the patients. POEM required a shorter operation time and postoperative stay compared to LHD (p < 0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (five mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p = 0.33). Two patients in the POEM group and one in the LHD were lost to follow-up. One patient in both groups died during the follow-up for unrelated causes. At a median follow-up of 24 months [15-30] for POEM and 31 months [15-41] for LHD (p < 0.05), 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p < 0.12). Four years after the treatment, the probability to have symptoms adequately controlled was > 90% for both groups (p = 0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; 24-h pH-monitoring showed however an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p < 0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p < 0.05).

Conclusion: POEM provides the same midterm results as LHD. This study confirms, however, a higher incidence of postoperative GERD with the former, even if its real significance needs to be further evaluated.
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http://dx.doi.org/10.1007/s11605-019-04465-wDOI Listing
March 2020

A Technical Modification to the Circular Stapling Anastomosis Technique During Minimally Invasive Ivor Lewis Procedure.

J Laparoendosc Adv Surg Tech A 2019 Dec 3;29(12):1585-1591. Epub 2019 Oct 3.

Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padova Center for Esophageal Diseases, University of Padova, Padova, Italy.

The circular stapled (CS) technique with transoral placement of the anvil is commonly used to perform the esophagogastric anastomosis during minimally invasive esophagectomy (MIE). The procedure is safe, efficient, and highly reproducible; however, the intersection between the circular plane of the stapler and the linear staple line of the esophageal stump can expose the anastomosis to the formation of dog-ears and, therefore, increase the risk of anastomotic leak (AL). We describe a simple modification of the CS technique that consists of folding the linear esophageal transection line with a stitch around the anvil shaft, to include the staple line in the resection during the EEA firing. We prospectively collected data on a small group of patients who underwent MIE for cancer using our modified CS technique. Feasibility has been evaluated as the percentage of cases in which the modified anastomosis technique has been carried out successfully with the formation of a complete anastomotic ring. Safety has been defined as the absence of procedure-related complications. MIE was performed in 10 patients using our modified CS technique. All the procedures were successfully completed with complete resection of the linear esophageal staple line and no intraoperative complications. Only one patient developed a postoperative AL that was only detected by barium swallow and did not cause any symptom or clinical sign. Our modified CS technique is feasible and did successfully prevent the occurrence of clinically relevant ALs in this small case series of patients.
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http://dx.doi.org/10.1089/lap.2019.0461DOI Listing
December 2019

Traction on the septum during transoral septotomy for Zenker diverticulum improves the final outcome.

Laryngoscope 2020 03 25;130(3):637-640. Epub 2019 Apr 25.

Department of Surgical, Oncological and Gastrointestinal Sciences, University of Padova, Clinica Chirurgica 3, Padova, Italy.

Objective: Transoral diverticulostomy/septotomy has become a popular treatment for patients with Zenker diverticulum (ZD). To improve the results of transoral stapler-assisted septotomy, a modification of the technique has been introduced. In this study, we aimed to compare the final outcome of such a modified transoral septotomy (MTS) with the results of traditional transoral septotomy (TTS) in patients with ZD.

Methods: Fifty-two consecutive patients with ZD underwent transoral stapler-assisted septotomy between 2010 and 2018. Symptoms were recorded and scored using a detailed questionnaire. Barium swallow, endoscopy, and manometry were performed before and after the procedure.

Results: Of the 52 patients forming the study population (male:female = 35:17), 25 had TTS and 27 had MTS. The patients' demographic and clinical parameters were similar in the two groups. No intraoperative mucosal lesions were detected, and the mortality was nil. The median time taken to complete the procedure was 25 minutes (interquartile range [IQR]: 22-35) for TTS, and 30 minutes (IQR: 25-36) for MTS (P < 0.07). The median follow-up was 69 months (IQR: 46-95) in the TTS group and 30 months (IQR: 25-35) in the MTS group. All patients in both groups had an improvement in their symptom score after the procedure, but the failure rates were 32% (8 of 25) after TTS and 3.7% (1 of 27) after MTS (P < 0.02). At univariate and multivariate analyses, the procedure was the only predictor of a positive final outcome.

Conclusion: Albeit with the intrinsic limitations of the study (retrospective, different time window, and different follow-up), traction on the septum during transoral septotomy improves the final outcome of this treatment in patients with ZD.

Level Of Evidence: 4 Laryngoscope, 130:637-640, 2020.
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http://dx.doi.org/10.1002/lary.28030DOI Listing
March 2020

Extending Myotomy Both Downward and Upward Improves the Final Outcome in Manometric Pattern III Achalasia Patients.

J Laparoendosc Adv Surg Tech A 2020 Feb 20;30(2):97-102. Epub 2019 Mar 20.

Department of Surgical, Oncological and Gastroenterological Sciences, School of Medicine, University of Padova, Padova, Italy.

Achalasia is currently classified in three manometric patterns. Pattern III is the least common pattern, and reportedly correlated with the worst outcome after all available treatments. We aimed to investigate the final outcome in pattern III achalasia patients after classic laparoscopic myotomy (CLM) as compared with a myotomy lengthened both downward and upward (long laparoscopic myotomy [LLM]). The study population consisted of 61 consecutive patients with a diagnosis of pattern III achalasia who underwent laparoscopic myotomy between 1997 and 2017. In CLM the total length of the myotomy was ≤9 cm, whereas myotomies extending both downward and upward to a length >9 cm were defined as LLM. Of the 61 patients considered, 24 had CLM and 37 had LLM. The postoperative improvement in symptom score differed between the two groups: it dropped from 22 (17-26) to 4 (0-8) in the CLM group and from 20 (17-24) to 3 (0-6) in the LLM group ( < .001). There were 8 of 24 failures (33.3%) in the former group and 4 of 37 (10.8%) in the latter group ( < .05). An abnormal acid exposure was detected after the treatment of CLM in 4 patients and after the treatment of LLM in 3 patients ( = n.s.). Although with the intrinsic limitations of this study (retrospective, different time windows of the two procedures, and different lengths of follow-up), the results indicate that extending the myotomy both downward and upward improves the final outcome of laparoscopic Heller-Dor surgery in pattern III achalasia patients. A longer myotomy does not affect any onset of postoperative gastroesophageal reflux.
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http://dx.doi.org/10.1089/lap.2019.0035DOI Listing
February 2020

A Thousand and One Laparoscopic Heller Myotomies for Esophageal Achalasia: a 25-Year Experience at a Single Tertiary Center.

J Gastrointest Surg 2019 01 20;23(1):23-35. Epub 2018 Sep 20.

Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università ed Azienda Ospedaliera di Padova, 2, via Giustiniani, 35128, Padua, Italy.

Background: The aim of this study was to assess the long-term outcome of laparoscopic Heller-Dor (LHD) myotomy to treat achalasia at a single high-volume institution in the past 25 years.

Methods: Patients undergoing LHD from 1992 to 2017 were prospectively registered in a dedicated database. Those who had already undergone surgical or endoscopic myotomy were ruled out. Symptoms were collected and scored using a detailed questionnaire; barium swallow, endoscopy, and manometry were performed before and after surgery; and 24-h pH monitoring was done 6 months after LHD.

Results: One thousand one patients underwent LHD (M:F = 536:465), performed by six staff surgeons. The surgical procedure was completed laparoscopically in all but 8 patients (0.8%). At a median of follow-up of 62 months, the outcome was positive in 896 patients (89.5%), and the probability of being cured from symptoms at 20 years exceeded 80%. Among the patients who had previously received other treatments, there were 25/182 failures (13.7%), while the failures in the primary treatment group were 80/819 (9.8%) (p = 0.19). All 105 patients whose LHD failed subsequently underwent endoscopic pneumatic dilations with an overall success rate of 98.4%. At univariate analysis, the manometric pattern (p < 0.001), the presence of a sigmoid megaesophagus (p = 0.03), and chest pain (p < 0.001) were the factors that predicted a poor outcome. At multivariate analysis, all three factors were independently associated with a poor outcome. Post-operative 24-h pH monitoring was abnormal in 55/615 patients (9.1%).

Conclusions: LHD can durably relieve achalasia symptoms in more than 80% of patients. The pre-operative manometric pattern, the presence of a sigmoid esophagus, and chest pain represent the strongest predictors of outcome.
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http://dx.doi.org/10.1007/s11605-018-3956-xDOI Listing
January 2019

Another Chapter of the : Is Primary Tumor Location a Prognostic Feature in Mutant Metastatic Colorectal Cancer?

Oncologist 2019 02 17;24(2):e77-e79. Epub 2018 Aug 17.

Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy.

Background: The prognostic value of primary tumor location (PTL) in patients with metastatic colorectal cancer (mCRC) was reported by recent analyses in wild-type patients. Here, we investigated the prognostic value of PTL in mutated mCRC patients.

Materials And Methods: PTL was defined as left or right if distal or proximal to the splenic flexure. Primary endpoint was overall survival (OS) according to PTL. Subgroup analyses were conducted according to time to metastases and mutation subtypes.

Results: Five hundred sixty-four patients were included. Left- and right-sided cases were 65% and 35%, respectively. No difference in OS was detected according to PTL (hazard ratio [HR] = 0.99, = .964). No difference in OS was observed in right versus left when looking at synchronous (HR 0.92, = .557) or metachronous (HR 1.07, = .807) patients.

Conclusion: No OS difference was detected in mutated mCRC. Molecular and clinical features able to improve prognosis and treatment strategies in this setting are needed.
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http://dx.doi.org/10.1634/theoncologist.2018-0180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369947PMC
February 2019

Cervical Esophageal Cancer Treatment Strategies: A Cohort Study Appraising the Debated Role of Surgery.

Ann Surg Oncol 2018 Sep 9;25(9):2747-2755. Epub 2018 Jul 9.

Department of Surgical, Oncological and Gastroenterological Sciences, Center for Esophageal Disease, University of Padova, Padua, Italy.

Background: Few studies have examined optimal treatment specifically for cervical esophageal carcinoma. This study evaluated the outcome of three common treatment strategies with a focus on the debated role of surgery.

Methods: All patients with cervical esophageal cancer treated at a single center were identified and their outcomes analyzed in terms of morbidity, mortality, and recurrence according to the treatment they received, i.e. surgery alone, definitive platinum-based chemoradiation (CRT), or CRT followed by surgery.

Results: The study population included 148 patients with cervical esophageal cancer from a prospective database of 3445 patients. Primary surgery was the treatment of choice for 56 (37.83%) patients, definitive CRT was the treatment of choice for 52 (35.13%) patients, and CRT followed by surgery was the treatment of choice for 40 (27.02%) patients. CRT-treated patients obtained 36.96% complete clinical response, with overall morbidity and mortality rates of 36.95 and 2.17%, respectively. Surgical complete resection was achieved in 71.88% of surgically treated cases, with morbidity and mortality rates of 52.17 and 6.25%, respectively. No significant survival difference existed among the three treatments, but patients who underwent surgery alone had a significantly lower stage of disease (p = 0.031). Compared with patients with complete response after CRT, surgery did not confer any significant survival benefit, and overall 5-year survival was lower than definitive CRT alone. In contrast, surgery improved survival significantly in patients with non-complete response after definitive CRT (p = 0.023).

Conclusions: Definitive platinum-based CRT should be the treatment of choice for cervical esophageal cancer. Surgery has a role for patients with non-complete response as it adds significant survival benefit, with acceptable morbidity and mortality.
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http://dx.doi.org/10.1245/s10434-018-6648-6DOI Listing
September 2018

Quality of life after laparoscopic sigmoid resection for uncomplicated diverticular disease.

Int J Colorectal Dis 2018 May 10;33(5):513-523. Epub 2018 Mar 10.

Department of Surgery, Oncology and Gastroenterology, Padova University, Padova, Italy.

Purpose: The study aimed to evaluate the QoL in patients who underwent elective surgery for uncomplicated diverticulitis using a recently developed diverticulitis quality of life questionnaire (DV-QoL).

Methods: All consecutive patients who underwent surgery for uncomplicated diverticulitis or who were hospitalized and treated conservatively for acute uncomplicated diverticulitis episodes in three referral centers, in a 5-year period, were included in the study. The 36-Item Short Form Survey and the DV-QoL were administered to the patients to assess their QoL before and after treatment of diverticular disease.

Results: Ninety-seven patients who underwent surgery, 44 patients who were treated conservatively, and 44 healthy volunteers were included in the study. DV-QoL scores correlated with SF-36 scores (p < 0.0001). The surgically treated patients reported a worse quality of life before treatment with respect to the patients treated conservatively (mean 21.12 surgical vs 15.41 conservative, p = 0.0048). The surgically treated patients presented better post-treatment global scores with respect to the conservatively treated patients (mean: 6.90 surgical vs 10.61 conservative, p = 0.0186). Covariance analysis confirmed that the differences between the pre- and post-treatment DV-QoL scores were significantly higher in the surgical (p = 0.0002) with respect to the non-surgical patients. As far as single items were concerned, differences between the two groups were found in the pre- and post-treatment "concerns" and "behavioral changes" DV-QoL items.

Conclusions: Sigmoidectomy reduces concerns about diverticulitis and behavioral changes due to the disease. Quality of life should be considered when referring patients with uncomplicated diverticulitis to surgery. Prospective studies are required to confirm this result.
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http://dx.doi.org/10.1007/s00384-018-3005-yDOI Listing
May 2018

The natural history of achalasia: Evidence of a continuum-"The evolutive pattern theory".

Dig Liver Dis 2018 Apr 26;50(4):342-347. Epub 2017 Nov 26.

Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, School of Medicine, Padova, Italy.

Background: It is currently unclear if the three manometric patterns of esophageal achalasia represent distinct entities or part of a disease continuum. The study's aims were: a) to test the hypothesis that the three patterns represent different stages in the evolution of achalasia; b) to investigate whether manometric patterns change after Laparoscopic-Heller-Dor (LHD).

Methods: We assessed the patients diagnosed with achalasia who underwent LHD as their first treatment from 1992 to 2016. Their symptoms were scored using a detailed questionnaire for dysphagia, food-regurgitation, and chest pain. Barium-swallow, endoscopy, and esophageal-manometry were performed before and 6 months after surgery.

Results: The study population consisted of 511 patients (M:F=283:228). Patients' demographic and clinical data showed that those with pattern III had a shorter history of symptoms, a higher incidence of chest pain, and a less dilated gullet (p<0.001). All patients with a sigmoid-shaped mega-esophagus had pattern I achalasia. One patient with a diagnosis of pattern III achalasia developed pattern II at a follow-up manometry before surgery. At a median follow-up of 30 months (IQR 12-56), the outcome of surgery was positive in 479 patients (91.7%). All patients with pattern I preoperatively had the same pattern after LHD, whereas more than 50% of patients with pattern III before treatment showed pattern I or II after surgery.

Conclusions: This study supports the hypothesis/theory that the different manometric patterns represent different stages in the evolution of the disease-where pattern III is the earliest stage, pattern II an intermediate stage, and pattern I the final stage.
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http://dx.doi.org/10.1016/j.dld.2017.11.012DOI Listing
April 2018

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.

Nat Commun 2017 11 22;8(1):1707. Epub 2017 Nov 22.

Department of Biosciences, Universita' degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.
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http://dx.doi.org/10.1038/s41467-017-01645-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700099PMC
November 2017

Computational modeling of abdominal hernia laparoscopic repair with a surgical mesh.

Int J Comput Assist Radiol Surg 2018 Jan 3;13(1):73-81. Epub 2017 Nov 3.

Department of Industrial Engineering, Centre for Mechanics of Biological Materials, University of Padova, via Venezia 1, 35131, Padua, Italy.

Purpose: Although new techniques and prostheses have been introduced in ventral hernia surgery, abdominal hernia repair still presents complications, such as recurrence, pain, and discomfort. Thus, this work implements a computational method aimed at evaluating biomechanical aspects of the abdominal hernia laparoscopic repair, which can support clinical research tailored to hernia surgery.

Methods: A virtual solid model of the abdominal wall is obtained from MRI scans of a healthy subject. The mechanical behavior of muscular and fascial tissues is described by constitutive formulations with specific parameters. A defect is introduced to reproduce an incisional hernia. Laparoscopic repair is mimicked via intraperitoneal positioning of a surgical mesh. Numerical analyses are performed to evaluate the mechanical response of the abdominal wall in healthy, herniated and post-surgery configurations, considering physiological intra-abdominal pressures.

Results: During the deformation of the abdominal wall at increasing pressures, a percentage displacement increment up to 6% is found in the herniated condition, while the mechanical behavior of the repaired abdomen is similar to the healthy one. In the pressure range between 8 mmHg and 55 mmHg, the herniated abdomen shows an incremental stiffness differing of 7% with respect to the healthy condition, while the post-surgery condition shows an increase of the incremental stiffness up to 58%.

Conclusions: This computational approach may be exploited to investigate different aspects of abdominal wall surgical repair, including mesh mechanical characteristics and positioning. Numerical modeling offers a helpful support for selecting the best-fitting prosthesis for customize pre-surgery planning.
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http://dx.doi.org/10.1007/s11548-017-1681-7DOI Listing
January 2018

A Procedure for the Automatic Analysis of High-Resolution Manometry Data to Support the Clinical Diagnosis of Esophageal Motility Disorders.

IEEE Trans Biomed Eng 2018 07 2;65(7):1476-1485. Epub 2017 Oct 2.

Objective: Degenerative phenomena may affect esophageal motility as a relevant social-health problem. The diagnosis of such disorders is usually performed by the analysis of data from high-resolution manometry (HRM). Inter- and intraobserver variability frequently affects the diagnosis, with potential interpretative and thus therapeutic errors, with unnecessary or worse treatments. This may be avoided with automatic procedures that minimize human intervention in data processing.

Methods: In order to support the traditional diagnostic process, an automatic procedure was defined considering a specific physiomechanical model that is able to objectively interpret data from HRM. A training set (N = 226) of healthy volunteers and pathological subjects was collected in order to define the model parameters distributions of the different groups of subjects, providing a preliminary database. A statistical algorithm was defined for an objective identification of the patient's healthy or pathological condition by comparing patient parameters with the database.

Results: A collection of HRMs including subjects of the training set has been built. Statistical relationships between parameters and pathologies have been established leading to a preliminary database. An automatic diagnosis procedure has been developed to compare model parameters of a specific patient with the database. The procedure was able to match the correct diagnosis up to 86% of the analyzed subjects.

Conclusion: The success rate of the automatic procedure addresses the suitability of the developed algorithms to provide a valid support to the clinicians for the diagnostic activity.

Significance: The objectivity of developed tools increases the reliability of data interpretation and, consequently, patient acceptance.
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http://dx.doi.org/10.1109/TBME.2017.2758441DOI Listing
July 2018

Endoscopic diode laser therapy for chronic radiation proctitis.

Lasers Med Sci 2018 Jan 11;33(1):35-39. Epub 2017 Sep 11.

3rd Surgical Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy.

The purpose of this study is to determine the effectiveness of endoscopic diode laser therapy in patients presenting rectal bleeding due to chronic radiation proctitis (CRP). A retrospective analysis of CRP patients who underwent diode laser therapy in a single institution between 2010 and 2016 was carried out. The patients were treated by non-contact fibers without sedation in an outpatient setting. Fourteen patients (median age 77, range 73-87 years) diagnosed with CRP who had undergone high-dose radiotherapy for prostatic cancer and who presented with rectal bleeding were included. Six required blood transfusions. Antiplatelet (three patients) and anticoagulant (two patients) therapy was not suspended during the treatments. The patients underwent a median of two sessions; overall, a mean of 1684 J of laser energy per session was used. Bleeding was resolved in 10/14 (71%) patients, and other two patients showed improvement (93%). Only one patient, who did not complete the treatment, required blood transfusions after laser therapy; no complications were noted during or after the procedures. Study findings demonstrated that endoscopic non-contact diode laser treatment is safe and effective in CRP patients, even in those receiving antiplatelet and/or anticoagulant therapy.
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http://dx.doi.org/10.1007/s10103-017-2323-6DOI Listing
January 2018

Giant elephantiasis and inguino-scrotal hernia.

PLoS Negl Trop Dis 2017 Jun 15;11(6):e0005494. Epub 2017 Jun 15.

Operational Research Unit, Doctors with Africa Cuamm, Beira, Mozambique.

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http://dx.doi.org/10.1371/journal.pntd.0005494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472255PMC
June 2017