Publications by authors named "Fausto Rosa"

103 Publications

Pancreaticoduodenectomy in octogenarians: The importance of "biological age" on clinical outcomes.

Surg Oncol 2021 Nov 24;40:101688. Epub 2021 Nov 24.

Gemelli Pancreatic Center, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy; CRMPG (Advanced Pancreatic Research Center), Largo Agostino Gemelli, 8, 00168, Rome, Italy; Università Cattolica del Sacro Cuore di Roma, Largo Francesco Vito 1, 00168, Rome, Italy.

Introduction: With the prolongation of life expectancy, an increasing number of elderly patients are evaluated for pancreatic surgery. However, the influence of increasing age on outcomes after pancreaticoduodenectomy (PD) is still unclear, especially in octogenarians. Aim of this study is to evaluate the perioperative characteristics and outcomes of octogenarians undergoing PD.

Methods: Data for 812 patients undergoing PD between 2019 and 2020 in 10 referral centers in Italy were reviewed. Patients aged 80 years or older were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients younger than 80 years. Propensity scores were calculated using 7 perioperative variables including gender, ASA score, neoadjuvant treatment (NAT), biliary stent positioning, type of surgical approach (open, laparoscopic, robot-assisted), associated vascular resections, type of lesion. Perioperative characteristics and short-term postoperative outcomes were compared before and after matching.

Results: Overall, 81 (10%) patients had 80 years or more. Before matching, octogenarians had a higher rate of ASA score≥ 3 (n = 35, 43.2% vs. n = 207, 28.3%; p = 0.005) and less frequently underwent NAT (n = 11, 13.6% vs. n = 213, 29.1%; p = 0.003). Matching was successfully performed for 70 octogenarians. After matching, no differences in preoperative and intraoperative characteristics were found. Postoperatively, ICU admission was more frequent in octogenarians (50% vs 30%; p = 0.01). Although in-hospital mortality was higher in octogenarians before matching (7.4% vs 2.9% in the younger cohort; p = 0.03), no difference was noted between the matched cohorts (p = 0.36). Postoperative morbidity was comparable between groups in the whole and selected populations. At the multivariate analysis, chronological age was not recognized as a prognostic factor for cumulative major complications, while ASA ≥3 was the only confirmed influencing feature (OR 2.98; 95%CI: 1.6-6.8; p = 0.009).

Conclusio: In high-volume centers, PD in octogenarians shows similar outcomes than younger patients. Age itself should not be considered an exclusion criterion for PD, but a focused preoperative assessment is essential for adequate patient selection.
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http://dx.doi.org/10.1016/j.suronc.2021.101688DOI Listing
November 2021

Quantitative assessment of the impact of COVID-19 pandemic on pancreatic surgery: an Italian multicenter analysis of 1423 cases from 10 tertiary referral centers.

Updates Surg 2021 Nov 24. Epub 2021 Nov 24.

Department of Surgery, Gemelli Pancreatic Center, Fondazione Policlinico Universitario "Agostino Gemelli", IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.

Few evidences are present on the consequences of coronavirus disease 2019 (COVID-19) pandemic on pancreatic surgery. Aim of this study is to evaluate how COVID-19 influenced the diagnostic and therapeutic pathways of surgical pancreatic diseases. A comparative analysis of surgical volumes and clinical, surgical and perioperative outcomes in ten Italian referral centers was conducted between the first semester 2020 and 2019. One thousand four hundred and twenty-three consecutive patients were included in the analysis: 638 from 2020 and 785 from 2019. Surgical volume in 2020 decreased by 18.7% (p < 0.0001). Benign/precursors diseases (- 43.4%; p < 0.0001) and neuroendocrine tumors (- 33.6%; p = 0.008) were the less treated diseases. No difference was reported in terms of discussed cases at the multidisciplinary tumor board (p = 0.43), mean time between diagnosis and neoadjuvant treatment (p = 0.91), indication to surgery and surgical resection (p = 0.35). Laparoscopic and robot-assisted procedures dropped by 45.4% and 61.9%, respectively, during the lockdown weeks of 2020. No difference was documented for post-operative intensive care unit accesses (p = 0.23) and post-operative mortality (p = 0.06). The surgical volume decrease in 2020 will potentially lead, in the near future, to the diagnosis of a higher rate of advanced stage diseases. However, the reassessment of the Italian Health Service kept guarantying an adequate level of care in tertiary referral centers. Clinicaltrials.gov ID: NCT04380766.
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http://dx.doi.org/10.1007/s13304-021-01171-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611384PMC
November 2021

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases: analysis of short- and long-term outcomes.

Langenbecks Arch Surg 2021 Oct 18. Epub 2021 Oct 18.

Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer (CRC) metastases. In recent years, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with limited peritoneal involvement. We report the evolution of CRS and HIPEC for colorectal peritoneal metastases at a tertiary referral center over a 10-year period.

Methods: Patients with colorectal peritoneal metastases undergoing CRS and HIPEC were included and retrospectively analyzed at a tertiary referral center from January 2006 to December 2015. Main outcomes included evaluation of grade III/IV complications, mortality rate, overall and disease-free survival, and prognostic factors influencing survival on a Cox multivariate analysis.

Results: Sixty-seven CRSs were performed on 67 patients during this time for colorectal peritoneal metastases. The median patient age was 57 years with 55.2% being female. The median peritoneal carcinomatosis index (PCI) was 7, with complete cytoreduction achieved in 65 (97%) cases. Grade > 2 complications occurred in 6 cases (8.9%) with no mortality. The median overall survival for the entire cohort was 41 months, with a 3-year overall survival of 43%. In case of complete cytoreduction, median overall and disease-free survival were 57 months and 36 months respectively, with a 3-year disease-free survival of 62%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival.

Conclusions: CRS and HIPEC for limited peritoneal metastases from CRC are safe and effective, with acceptable morbidity. In selected patients, it offers a highly favorable long-term outcomes.
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http://dx.doi.org/10.1007/s00423-021-02353-zDOI Listing
October 2021

The impact of gastrojejunostomy orientation on delayed gastric emptying after pancreaticoduodenectomy: a single center comparative analysis.

HPB (Oxford) 2021 Sep 24. Epub 2021 Sep 24.

Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center) Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS; Largo Agostino Gemelli, 8, 00168, Rome, Italy; Università Cattolica Del Sacro Cuore di Roma, Largo Francesco Vito 1, 00168, Rome, Italy.

Background: Delayed gastric emptying (DGE) represents the most frequent complication after pancreaticoduodenectomy (PD). Aim of this study was to evaluate the impact of gastrojejunostomy (GJ)orientation on DGE incidence after PD.

Methods: One-hundred and twenty-one consecutive PDs were included in the analysis and divided in the horizontal (H-GJ group) and vertical GJ anastomosis groups (V-GJ group). Postoperative data and the value of the flow angle between the efferent jejunal limb and the stomach of the GJ anastomosis at the upper gastrointestinal series were registered.

Results: Seventy-five patients (62%)underwent H-GJ, while 46 patients (38%)underwent V-GJ. The incidence of DGE was significantly lower in the V-GJ group as compared to the H-GJ group (23.9%vs45.3%; p = 0.02). V-GJ was also associated to a less severe DGE manifestation (p = 0.006). The flow angle was significantly lower in case of V-GJ as compared to H-GJ (24.5°vs37°; p = 0.002). At the multivariate analysis, ASA score≥3 (p = 0.02), H-GJ (p = 0.03), flow angle>30°(p = 0.004) and Clavien-Dindo≥3 (p = 0.03) were recognized as independent prognostic factors for DGE. These same factors were independent prognostic features also for a more severe DGE manifestation.

Conclusion: VGJ and the more acute flow angle appear to be associated to a lower incidence rate and severity of DGE. This modified technique should be considered by surgeons in order to reduce postoperative DGE occurrence.
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http://dx.doi.org/10.1016/j.hpb.2021.09.015DOI Listing
September 2021

Role of serum procalcitonin in predicting the surgical outcomes of acute calculous cholecystitis.

Langenbecks Arch Surg 2021 Nov 2;406(7):2375-2382. Epub 2021 Jul 2.

Emergency Surgery and Trauma, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, 00168, Rome, Italy.

Background: Acute calculous cholecystitis (AC) is a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation. In the preoperative planning, the severity of AC should be considered as well as time of onset of symptoms and patient comorbidities. The aim of the present study was to investigate the role of an early PCT assessment in the emergency department in predicting the outcomes of laparoscopic surgery for AC.

Study Design: Retrospective, mono-centric study conducted in a teaching urban hospital. We evaluated all patients admitted to our ED from January 1st, 2015, to December 31st, 2019, underwent laparoscopic cholecystectomy for AC having a preoperative PCT determination in ED.

Results: A total of 2285 patients in our ED were admitted for AC. Among them 822 patients were treated surgically, 174 had a PCT determination in ED. Median age was 63 [50-74]. Overall, 33 patients (19.0%) had major complications (MC): 32 needed an open surgery conversion, and 3 among them deceased. Multivariate analysis demonstrated that PCT, WBC, BUN, and CCI were significantly associated to MC in our cohort. When we calculated the area under the ROC curve with regard to MC, a procalcitonin value > 0.09 at admission had sensitivity = 84.8% [68.1-94.9] and specificity = 51.8% [43.2-60.3] for the occurrence of MC.

Conclusion: Our results, suggest that a PCT > 0.09 ng/mL at ED admission, could be associated to a poor surgical outcome in patients treated by laparoscopic surgery for AC.
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http://dx.doi.org/10.1007/s00423-021-02252-3DOI Listing
November 2021

Laparoscopic vs. open resection of gastrointestinal stromal tumors (GISTs) from gastric origin: different approaches for different diseases.

Minerva Surg 2021 Aug 28;76(4):372-381. Epub 2021 May 28.

Department of Digestive Surgery, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

Background: Although minimally-invasive techniques are currently recognized as effective and validated treatment for small gastric gastrointestinal stromal tumors (GISTs), the role of laparoscopy is not yet established. The aim of this study was to evaluate the outcomes of laparoscopic treatment of gastric GISTs compared to the results obtained in a group of patients treated with conventional surgery.

Methods: A retrospective analysis was performed, using a prospectively maintained comprehensive database of 100 patients treated for gastric GIST in the period from 2000 to 2015. Thirty-six patients were treated laparoscopically, and 64 patients underwent conventional surgery. The analyzed medical data included clinical and pathological features of removed tumors, perioperative parameters as well as short and long-term results of surgical treatment.

Results: Histopathological examination confirmed radical resections for all patients. No deaths were reported in the 90-day postoperative period. Patients in laparoscopic group had significantly shorter length of hospital stay (5.5 vs. 7 days, P<0.0001), fewer extended and combined surgical procedures (11.2% vs. 34.4% and 2.8% vs. 39%; P=0.02 and P<0.001, respectively), and a smaller tumor size compared to laparotomic group (3 vs. 6 cm, P<0.0001). The median postoperative follow-up for the entire study population was 42 months. During this period, 11 patients died and 4 of them developed a tumor recurrence. None of them was in the laparoscopic group.

Conclusions: Laparoscopy in the treatment of gastric GISTs has unquestionable advantages, but its choice is strictly related to tumor features.
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http://dx.doi.org/10.23736/S2724-5691.21.08574-9DOI Listing
August 2021

Adhesive small bowel obstruction in elderly patients: a single-center analysis of treatment strategies and clinical outcomes.

Scand J Gastroenterol 2021 Jul 7;56(7):784-790. Epub 2021 May 7.

Digestive Surgery Unit, Fondazione Policlinico Agostino Gemelli IRCCS di Roma, Rome, Italy.

Introduction: The incidence of adhesive bowel obstruction (ASBO) progressively increases with age. Strong evidences on the influencing role of age on ASBO clinical course and management are still lacking. Aim of this study is to retrospectively analyze the clinical outcomes of patients older than 65 years of age admitted to a tertiary referral Emergency Department with a diagnosis of ASBO.

Materials And Methods: We reviewed the clinical records of patients admitted for ASBO in the period 2014-2019. Patients were divided in elderly (≥65 years) and non-elderly (<65 years). Primary endpoint was to compare the all-cause in-hospital mortality and the occurrence of major complications in the two groups. Secondary endpoint was a comparison of clinical presentation, clinical course and management.

Results: We enrolled 285 elderly and 492 non-elderly patients. Vomit was more frequent in the elderly (51.9% vs 34.6%;  < .001), while no difference was evidenced for the remaining symptoms of ASBO presentation. A higher rate of non-operative management (NOM) (26.3% vs 16.5%;  = .010), ICU admission (16% vs 0.6%;  < .001), mortality (2.1% vs 0.2%;  = .007) and cumulative major complications (8.8% vs 3.3%;  = .001), as well as a prolonged hospitalization (8.2 vs 5.4 days;  < .001) was evidenced in the ≥65 years group. Multivariate analysis identified increasing age (OR:2.8; 95%CI:1.09-7.2;  = .040) and Charlson comorbidity index ≥ 2 (OR:2.5; 95% CI:1.2-6.4;  = .050) as the only independent predictors of cumulative major complications.

Conclusions: Despite the similarity in terms of clinical presentation, elderly patient present higher mortality rate and occurrence of major complications. A comprehensive geriatric assessment is recommended to optimize the diagnostic and clinical strategies in case of ASBO.
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http://dx.doi.org/10.1080/00365521.2021.1921256DOI Listing
July 2021

The role of mesopancreas excision for ampullary carcinomas: a single center propensity-score matched analysis.

HPB (Oxford) 2021 Oct 18;23(10):1557-1564. Epub 2021 Apr 18.

Pancreatic Surgery Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; CRMPG (Advanced Pancreatic Research Center), Largo A. Gemelli, 8, 00168, Roma, Italy; Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Roma, Italy.

Background: Few evidences are available on the prognostic role of mesopancreas excision(MPe) for ampullary cancers(ACs). Aim of this study was to compare the long-term outcomes between pancreaticoduodenectomy(PD) with(PD-MPe group) and without(sPD group) MP.

Methods: Thirty-seven sPDs were matched and compared to 37 PD-MPes for perioperative outcomes, recurrence rate, disease-free(DFS) and overall survival(OS).

Results: The PD-MPe technique related to a significantly higher number of harvested lymph nodes[16 (±6)] as compared to the sPD [10 (±5); p < 0.0001]. Tumor recurrence was more frequent in the sPD cohort[21 (56.8%) vs 12 (32.4%) in the PD-MPe population; p = 0.03]. Although not statistically different, PD-MPe was associated with a better DFS(40% vs 35.7% for sPD; p = 0.08) and OS(59.3% vs 39.1% for sPD; p = 0.07). At the multivariate analysis, a higher number of lymph nodes retrieved and a more extensive lymphovascular clearance reached with the MPe technique, together with lymph nodes metastases, were recognized as independent prognostic factors for a worse OS and DFS.

Conclusion: The PD-MPe technique is associated with a better oncological radicality thanks to the higher number of retrieved lymph nodes and to the more appropriate tumor clearance. This reflects in a lower incidence of tumor relapse and in improved outcomes in terms of OS and DFS.
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http://dx.doi.org/10.1016/j.hpb.2021.03.011DOI Listing
October 2021

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

Langenbecks Arch Surg 2021 Sep 11;406(6):1847-1857. Epub 2021 Mar 11.

Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent.

Methods: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed.

Results: A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05).

Conclusions: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.
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http://dx.doi.org/10.1007/s00423-021-02102-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481141PMC
September 2021

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

Langenbecks Arch Surg 2021 Jun 21;406(4):1071-1080. Epub 2021 Feb 21.

Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent.

Methods: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed.

Results: A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05).

Conclusions: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.
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http://dx.doi.org/10.1007/s00423-021-02137-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208915PMC
June 2021

Challenges in Crohn's Disease Management after Gastrointestinal Cancer Diagnosis.

Cancers (Basel) 2021 Feb 2;13(3). Epub 2021 Feb 2.

Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.
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http://dx.doi.org/10.3390/cancers13030574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867285PMC
February 2021

Early Procalcitonin Assessment in the Emergency Department in Patients with Intra-Abdominal Infection: An Excess or a Need?

Surg Infect (Larchmt) 2021 Oct 2;22(8):787-796. Epub 2021 Feb 2.

Emergency Surgery and Trauma, Fondazione Policlinico Universitario A, Gemelli, IRCCS, Rome, Italy.

Intra-abdominal infection (IAI) is a wide range of intra-abdominal disease. Management involves empirical therapy and source control. Procalcitonin (PCT) has been suggested to assist in defining individual infection status and delivering individualized therapy. The aim of this study was to investigate the effects on patient outcomes of an early procalcitonin (PCT) assessment (in the emergency department [ED]) in patients with IAI. This was a retrospective, mono-centric study evaluating consecutive patients admitted to the ED from 2015 to 2019 with diagnosis of IAI. According to whether there had been PCT determination in the ED, patients were divided into no ePCT determination (no-ePCT) and early PCT determination in the ED (ePCT). The primary endpoint was the intra-hospital mortality rate. Secondary endpoints were occurrence of major complications and length of hospital stay (LOS). The propensity score match (PSM) was generated using a logistic regression model on the baseline covariates considered to be potentially influencing the decision to determine PCT in the ED and confounding factors identified as significant at a preliminary statistical analysis with respect to in-hospital death. A series of 3,429 patients were included. The ePCT group consisted to 768 (22.4%), whereas the no-ePCT group contained 2,661 patients (77.6%). When the PSM was matched to the two groups, no significant difference was observed. Considering patients with uncomplicated infections, the PCT determination was associated with a higher mortality rate. We found no significant differences regarding outcomes with the exception of LOS, which was slightly longer in the ePCT group. However, we observed a tendency toward a minor difference in the number of complications in the ePCT group, in particular a reduced rate of progression to sepsis. Early PCT determination could be irrelevant in IAIs. The PCT value may be cost-effective and possibly improve the prognosis in cIAIs. Further research is needed to understand the optimal use of PCT, including in combination with other emerging diagnostic tests.
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http://dx.doi.org/10.1089/sur.2020.373DOI Listing
October 2021

Management of acute cholecystitis in elderly patients: A propensity score-matched analysis of surgical vs. medical treatment.

Dig Liver Dis 2021 Dec 23;53(12):1620-1626. Epub 2021 Jan 23.

Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Acute cholecystitis (AC) is a life-threatening emergency in elderly patients.

Aims: To compare the commonly used management strategies for elderly patients with AC as well as resulting morbidity, mortality and length of hospital stay (LOS).

Methods: All patients ≥ 65 years admitted to our emergency department for AC between January 1st, 2014 and December 31st, 2018 were included in the study. We compared patients that received medical treatment to patients who received operative procedures. In order to correct for baseline covariates and factors associated to clinical management, we used a 1:1 propensity score matching (PSM) analysis. The primary outcome was the overall in-hospital mortality. Secondary outcomes included occurrence of major complications and LOS.

Results: A total of 1075 patients were enrolled: 483 patients received a medical treatment and 592 patients underwent interventional procedures. After PSM, 770 patients (385 for each treatment group) were included in the analysis. The analysis revealed that both mortality and cumulative major complications were similar in medical and interventional group. We found that among comorbidities, Charlson comorbidity index and congestive heart failure were significantly higher in the medical treatment group (5 [4-6] vs. 4 [3-6] and 11.7% vs. 4.7%, respectively; p<0.001). LOS was slightly lower in the medical treatment group (7.0 days [4.9-11.1] vs. 7.9 [4.9-13.5]; p = 0.046).

Conclusion: Medical management outcomes for AC in elderly patients were similar to operative treatments in terms of mortality and cumulative major complications. A conservative approach should always be considered.
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http://dx.doi.org/10.1016/j.dld.2021.01.011DOI Listing
December 2021

EUS-guided fine needle tattooing (EUS-FNT) for preoperative localization of small pancreatic neuroendocrine tumors (p-NETs): a single-center experience.

Surg Endosc 2021 01 21;35(1):486-492. Epub 2020 Sep 21.

Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: and study aims Pancreatic neuroendocrine tumors (pNETs) can be difficult to detect intra-operatively. The aim of this paper is to evaluate the safety and efficacy of preoperative endoscopic ultrasound guided fine needle tattooing (EUS-FNT) to facilitate intra-operative detection of pNETs.

Patients And Methods: Sixteen patients with pNETs (8 insulinoma and 8 non-functional pancreatic neuroendocrine tumors) underwent EUS-FNT. The procedure was carried out using the conventional curvilinear EUS. Tattooing was performed by intralesional injection of 1-2 mL of Spot® ink (Spot®, GI Supply, Comp Hill, PA, US) using a standard 22 gauge EUS-FNA needle.

Results: All identified pNETs could be tattooed in one session. The procedure was well tolerated in all patients without any complication. The time interval between tattooing and surgery was between 1 and 565 days (mean of 52 days). Nine patients underwent open and seven laparoscopic surgery. The tattooed lesions could be recognized in all but one patient. In one patient, a small hematoma secondary to the EUS-FNT was observed. Pathological examination of the resection specimen showed local R0 resection in all cases, and no interference with the specimen evaluation was encountered.

Conclusions: Our results suggest that EUS-guided FNT is a safe and useful method to mark preoperatively small (≤ 2 cm) pNETs.
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http://dx.doi.org/10.1007/s00464-020-07996-5DOI Listing
January 2021

From biology to surgery: One step beyond histology for tailored surgical treatments of gastric cancer.

Surg Oncol 2020 Sep 5;34:86-95. Epub 2020 Apr 5.

Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore di Roma, Italy.

Gastric cancer is the third most common cause of cancer related death. Although its incidence is globally declined, prognosis remains dismal in the Western hemisphere, while better outcomes are evidenced in Asian countries. Endoscopic or surgical resection with or without lymphadenectomy represents the only chance of cure, with limited improvements of the prognosis in case of associated chemotherapy in a neoadjuvant or adjuvant setting. This could be mainly attributed to the uniform fashion of treatment of gastric cancer, mainly based on the histological features, that usually do not reflect the complexity of the disease. With the recent introduction of genomic technologies and new generation sequencing techniques, gastric cancer biology is now investigated in great details. This has brought to the publication of three main molecular classifications, based on the underlying molecular biology of gastric cancer. Although only few clinical reports are currently present in literature, the identification of gastric cancer molecular subtypes has shown interesting findings that may pave the way to a tailored clinical and surgical management. The aim of this review is, thus, to give a comprehensive overview of the current molecular classifications as compared to the available histopathological ones, also focusing on the potential clinical and surgical benefits and the future perspectives for a more personalized treatment of gastric cancer.
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http://dx.doi.org/10.1016/j.suronc.2020.04.004DOI Listing
September 2020

Possible impact of COVID-19 on gastric cancer surgery in Italy.

Minerva Chir 2020 10 6;75(5):380-381. Epub 2020 Aug 6.

Department of Digestive Surgery, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

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http://dx.doi.org/10.23736/S0026-4733.20.08381-9DOI Listing
October 2020

Acute Diverticulitis in Elderly Patients: Does Age Really Matter?

Dig Dis 2021 2;39(1):33-41. Epub 2020 Jun 2.

Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Objective: Contrasting results are reported on the clinical course of acute diverticulitis (AD) in the geriatric population. The aim of this study is to compare the AD clinical outcomes between patients aged up to 80 years and those ≥80 years.

Methods: A total of 1,139 patients were enrolled: 276 patients aged ≥80 years were compared with a group of 863 patients aged <80 years. The primary outcome was to compare the overall mortality. Secondary outcomes included major complications, in-hospital length of stay (LOS), and need for surgical procedures.

Results: Patients ≥80 years with AD had different clinical presentation compared with younger patients: they had less fever (21.4 vs. 35.2%; p < 0.001) and abdominal pain (47.8 vs. 65.6%; p < 0.001) rates, but a higher digestive tract bleeding (31.5 vs. 12.3%; p < 0.001) and fatigue (12.7 vs. 7.1%; p = 0.004) rates. Median LOS, cumulative major complications, and mortality rates were higher for patients ≥80 years.Multivariate analysis identified age, absence of abdominal pain, and dyspnea at presentation as independent predictors of intrahospital death or major complications.

Conclusions: Patients with AD and age ≥80 years have a higher mortality rate and cumulative major complications as compared with younger patients. Invasive treatments were associated to a poor prognosis in this group.
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http://dx.doi.org/10.1159/000509049DOI Listing
February 2021

Propensity score-matched comparison of short- and long-term outcomes between surgery and endoscopic submucosal dissection (ESD) for intestinal type early gastric cancer (EGC) of the middle and lower third of the stomach: a European tertiary referral center experience.

Surg Endosc 2021 06 1;35(6):2592-2600. Epub 2020 Jun 1.

Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00166, Rome, Italy.

Background: Despite the comparable results between ESD and gastrectomy reported in multiple Asiatic studies, limited data are currently present on the long-term efficacy of ESD for EGC in Western countries. The aim of this study was to compare the short- and long-term outcomes of the endoscopic submucosal dissection and surgery for non-diffuse early gastric cancer treatment in a Western cohort of patients.

Methods: All patients with a diagnosis of intestinal type EGC located in the middle and lower third of the stomach from 2005 to 2015 were enrolled in the study. All patients completed a 5-year follow-up. Patients were divided according to the procedure performed (ESD/subtotal gastrectomy). The two groups were matched for age, gender, ASA score, tumor dimension, and grade of infiltration (mucosa/submucosa).

Results: After matching, 84 patients (42 per group) were included in the analysis. Peri-procedural morbidity rate was 7.1% and no difference was observed between the two groups (4.8% vs 9.5% for ESD and STG groups, respectively; p = 0.3). Similar results in terms of 5-year OS and DFS were observed for ESD and STG (77.7% vs 71.8% ; p = 0.78 and 74.9% vs 72% ; p = 0.7, respectively). At the multivariate analysis, ASA3 score was recognized as the only negative predictor factor for the 5-year OS (OR 6.2; 95% CI 2.2-16.8; p < 0.001). Regarding the DFS, both ASA3 score (OR 4.4; 95% CI 1.7-10.9; p < 0.001) and submucosal infiltration(OR 5.1; 95% CI 1.2-22.4 ; p = 0.02) were identified as independent risk factors for a worse outcome.

Conclusions: Our results confirm the safety and feasibility ESD for EGC treatment in a Western setting. In addition, this is one of the few reports showing comparable results both in terms of short- and long-term outcomes between ESD and surgery for intestinal type ECG treatment in Western countries.
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http://dx.doi.org/10.1007/s00464-020-07677-3DOI Listing
June 2021

Total mesopancreas excision for periampullary malignancy: a single-center propensity score-matched comparison of long-term outcomes.

Langenbecks Arch Surg 2020 May 24;405(3):303-312. Epub 2020 Apr 24.

Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Purpose: Few comparative studies are available on the long-term prognostic role of mesopancreas (MP) excision after pancreaticoduodenectomy (PD). We compared the long-term outcomes of patients undergoing standard PD (sPD) and PD with MP excision (PD-MPe).

Methods: Sixty sPDs were compared to 60 matched PD-MPe patients for intraoperative and postoperative data, histopathological findings, and long-term outcomes.

Results: R0 rate was similar in the two groups (p = 0.17). However, PD-MPe related to a lower rate of MP resection margin positivity (16.7% vs 5%; p = 0.04) and to a higher harvested lymph nodes number (19.8 ± 7.6 vs 10.1 ± 5.1; p < 0.0001). Local tumor recurrence was more frequent in the sPD cohort (55.5% vs 26.8% in the PD-MPe group; p = 0.002), with a consequent worse disease-free survival (DFS) (14.8% vs 22.3%; p = 0.04). An inferior 5-year overall survival (OS) was noted in case of MP margin positivity compared with MP margin negativity (0% vs 29%; p < 0.0001). MP positivity resulted as an independent prognostic factor for both a worse OS and DFS at the multivariate analysis.

Conclusion: PD-MPe offers clinical advantages in terms of MP resection margin status, local recurrence, long-term mortality, and DFS. The lower MP positivity rate, achieved with PD-MPe, leads to better outcomes both in terms of OS and DFS.
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http://dx.doi.org/10.1007/s00423-020-01873-4DOI Listing
May 2020

Laparoscopic Gastrectomy After Neoadjuvant Chemotherapy: Still Far From Solid Conclusions.

JAMA Surg 2020 05;155(5):449-450

Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.1001/jamasurg.2019.5943DOI Listing
May 2020

Postoperative hyperglycemia affects survival after gastrectomy for cancer: A single-center analysis using propensity score matching.

Surgery 2020 05 3;167(5):815-820. Epub 2019 Dec 3.

Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Background: No data are present currently on the potential correlation between postoperative hyperglycemia and long-term outcomes after gastric surgery for cancer. The aim of this study was to investigate the effects of postoperative hyperglycemia on survival after curative gastrectomy for cancer.

Methods: All patients who underwent gastric surgery for cancer with curative intent were reviewed retrospectively. Diabetic patients and patients who needed pancreatic resection were excluded. In all patients, a prepared intravenous infusion of NaCl and carbohydrates (Isolyte Baxter 2,000 mL/day; glucose 50.0 g/L;Ringers lactate 1,000 mL/day) was used, and the patients were kept nil by mouth until the fourth postoperative day. The glucose levels were monitored during the first 72 hours. The study population was divided into normoglycemic and hyperglycemic patients according to the blood glucose level (<140 mg/dL and ≥140 mg/dL, respectively). The 2 groups were matched for age, sex, type of operative procedure, TNM status, and lymph node status.

Results: After matching, 104 patients were included for the analysis. Perioperative morbidity accounted for 18.3% with a greater rate for hyperglycemic patients (12% vs 31%; P = .018). When compared with normoglycemic patients, hyperglycemic patients had worse overall survival (45% vs 57%; P = .05) and worse disease-free survival (46% vs 68%; P = .02). On the multivariate analysis, hyperglycemia was an independent risk factor for a worse overall and disease-free survival.

Conclusion: Postoperative hyperglycemia owing to surgical stress conditions can affect postoperative outcomes. Additionally, hyperglycemia may be a factor that promotes gastric cancer progression.
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http://dx.doi.org/10.1016/j.surg.2019.11.006DOI Listing
May 2020

How Should We Measure the Quality of Lymphadenectomy for Gastric Cancer? Anatomical Versus Numerical Criterion.

J Gastrointest Cancer 2020 Sep;51(3):887-892

Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy.

Aim: To compare anatomical with numerical criterion to measure the quality of lymphadenectomy for gastric cancer.

Patients And Methods: We analyzed 447 gastric cancer patients with resectable tumor stage (R0 resection) with at least 16 examined lymph nodes.

Results: Of 447 patients, 82.6% underwent D2 lymphadenectomy for a median of total examined lymph nodes of 28. The 7-year disease-specific survival rate for the whole sample was 71.4%. Survival was significantly different between patients treated with D2 and D1 lymphadenectomy (77.4% versus 44.3%; p < 0.001) and between patients with total examined lymph nodes ≥ 28 and < 28 (74.5% versus 62.3%; p = 0.041). Anatomical criterion significantly differentiated 7-year survival in patients stratified according to a numerical parameter.

Conclusion: We should still consider the anatomical criterion as the best item to measure the quality of lymphadenectomy for gastric cancer.
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http://dx.doi.org/10.1007/s12029-019-00321-xDOI Listing
September 2020

Extended Lymphadenectomy for Gastroesophageal Carcinoma in Western Patients.

J Am Coll Surg 2019 11;229(5):520

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1016/j.jamcollsurg.2019.06.003DOI Listing
November 2019

Acute pancreatitis in oldest old: a 10-year retrospective analysis of patients referred to the emergency department of a large tertiary hospital.

Eur J Gastroenterol Hepatol 2020 02;32(2):159-165

Digestive Surgery Unit, Department of Surgery, CRMP (Gemelli Pancreatic Advanced Research Center).

Objective: Contrasting results are reported on the clinical course of acute pancreatitis (AP) in the geriatric population. The aim of this study is to compare the AP clinical outcomes between patients aged from 65 to 79 years and those over 80 years.

Methods: A total of 115 patients over 80 years (oldest old) were compared to a group of 236 patients aged 65-79 years (elderly). Clinicodemographic, biochemical, and radiological data were reviewed. The primary outcome was to compare the overall mortality. Secondary outcomes included intensive care unit (ICU) admission, in-hospital length of stay (LOS), and need for surgical procedures.

Results: Laboratory values at admission were similar between the two groups. Over 80 patients presented a lower rate of abdominal symptoms (68.7% vs. 81.4%; P = 0.008), a higher mortality (14.8% vs. 3.5%; P = 0.003), and ICU admission (13.9% vs. 3.8%; P = 0.001) rates. Median LOS was comparable between the two groups. Multivariate analysis identified age [odds ratio (OR): 3.56; 95% confidence interval (CI): 1.502-8.46; P = 0.004], a higher Ranson score (OR: 3.22; 95% CI: 1.24-8.39; P = 0.016), and the absence of abdominal pain (OR: 2.94; 95% CI: 1.25-6.87; P = 0.013) as independent predictors of mortality. Conversely, only age (OR: 3.83; 95% CI: 1.55-9.44; P = 0.003) and a more severe AP (OR: 3.56; 95% CI: 1.95-6.89; P = 0.041) were recognized as influencing ICU admission. Only the operative treatment (OR: 2.805; 95% CI: 1.166-5.443; P = 0.037) was evidenced as independent risk factor for LOS (OR: 3.74; 95% CI: 1.031-6.16; P = 0.003).

Conclusion: Oldest old patients have a higher mortality and ICU admission rate as compared to the other subgroups of elderly. Early diagnosis and prompt treatment are key elements to improve outcomes in this frailer population.
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http://dx.doi.org/10.1097/MEG.0000000000001570DOI Listing
February 2020

Full Robotic Distal Pancreatectomy: Safety and Feasibility Analysis of a Multicenter Cohort of 236 Patients.

Surg Innov 2020 Feb 9;27(1):11-18. Epub 2019 Aug 9.

Università Cattolica del Sacro Cuore of Rome, Fondazione Policlinico "A Gemelli" IRCCS of Rome, Rome, Italy.

. Despite the widespread use of the robotic technology, only a few studies with small sample sizes report its application to pancreatic diseases treatment. Our aim is to present the results of a multicenter study on the safety and feasibility of robot-assisted distal pancreatectomy (RDP). . All RDPs for benign, borderline, and malignant diseases performed in 5 referral centers from 2008 to 2016 were included. Perioperative outcomes were evaluated. . Two hundred thirty-six patients were included. Spleen preservation was performed in 114 cases (48.3%). Operative time was 277.8 ± 93.6 minutes. Progressive improvement in operative time was observed over the study period. Conversion rate was 6.3%. Morbidity occurred in 102 cases (43.2%), mainly due to grade A fistulas. Reoperation was required in 10 patients. Postoperatively, 2 patients died of sepsis due to a grade C fistula. Hospital readmission was necessary in 11 cases. A R0 resection was always achieved, with a mean number of 16.2 ± 15 harvested lymph nodes. . To our knowledge, this is one of the largest RDP series. Safety and feasibility including the low conversion rate, the high spleen preservation rate, the adequate operative time, and the acceptable morbidity and mortality rates confirm the validity of this technique. Appropriate oncological outcomes have been also obtained.
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http://dx.doi.org/10.1177/1553350619868112DOI Listing
February 2020

Short-term and long-term outcomes after robot-assisted versus laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors (pNETs): a multicenter comparative study.

Langenbecks Arch Surg 2019 Jun 4;404(4):459-468. Epub 2019 May 4.

Fondazione Policlinico "A.Gemelli" IRCCS of Rome, CRMPG (Gemelli Pancreatic Advanced Research Center), Università Cattolica del Sacro Cuore of Rome, Largo Agostino Gemelli 8, 00166, Rome, Italy.

Purpose: Minimally invasive surgery has increasingly gained popularity as a treatment of choice for pancreatectomy with encouraging initial results in robotic distal pancreatectomy (RDP). However, few data are available on the comparison between RDP and laparoscopic distal pancreatectomy (LDP) for pancreatic neuroendocrine tumors (pNETs). Our aim, thus, is to compare perioperative and long-term outcomes as well as total costs of RDP and LDP for pNETs.

Methods: All RDPs and LDPs for pNETs performed in four referral centers from 2008 to 2016 were included. Perioperative outcomes, histopathological results, overall (OS) and disease-free survival (DFS), and total costs were evaluated.

Results: Ninety-six RDPs and 85 LDPs were included. Demographic and clinical characteristics were comparable between the two cohorts. Operative time was 36.5 min longer in the RDP group (p = 0.009) but comparable to LDP after removing the docking time (247.9 vs 233.7 min; p = 0.6). LDP related to a lower spleen preservation rate (44.7% vs 65.3%; p < 0.0001) and higher blood loss (239.7 ± 112 vs 162.5 ± 98 cc; p < 0.0001). Advantages in operative time for RDP were documented in case of the spleen preservation procedures (265 ± 41.52 vs 291 ± 23 min; p = 0.04). Conversion rate, postoperative morbidity, and pancreatic fistula rate were similar between the two groups, as well as histopathological data, OS, and DFS. Significant advantages were evidenced for LDP regarding mean total costs (9235 (± 1935) € vs 11,226 (± 2365) €; p < 0.0001).

Conclusions: Both RDP and LDP are safe and efficacious for pNETs treatment. However, RDP offers advantages with a higher spleen preservation rate and lower blood loss. Costs still remain the main limitation of the robotic approach.
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http://dx.doi.org/10.1007/s00423-019-01786-xDOI Listing
June 2019

Acute pancreatitis in elderly patients: a single-center retrospective evaluation of clinical outcomes.

Scand J Gastroenterol 2019 Apr 24;54(4):492-498. Epub 2019 Mar 24.

b Medicina D'Urgenza , Fondazione Policlinico Universitario A. Gemelli IRCCS , Roma, Italia.

Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated. We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly  (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures. We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%;  < .001), ICU admission rate (18.9% vs 6.3%;  < .001) and prolonged length of hospital stay (9 (6-14) vs 7 (5-11.7) days;  = .01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645-7.555;  = .001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11-27.41; <.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46-30.27;  = .001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission. Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.
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http://dx.doi.org/10.1080/00365521.2019.1588369DOI Listing
April 2019

Billroth II reconstruction in gastric cancer surgery: A good option for Western patients.

Am J Surg 2019 11 13;218(5):940-945. Epub 2019 Mar 13.

Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: The aim of this study is to report the short and long-term results of a cohort of patients who underwent Billroth II (BII) Distal Gastrectomy (DG) for gastric cancer (GC), in a tertiary referral Western center.

Methods: From January 2005 to December 2015, a prospective observational study was conducted in candidate patients to elective gastrectomy for cancer.

Results: Among 514 patients observed with GC, a series of 258 patients underwent BII DG for middle/lower third GC. Postoperative mortality and complication rates were 1.5% and 12.4% respectively. The overall and disease-free 5-year survival rates were 78% and 69%, respectively. Young age, lymph nodes retrieved, radicality of resection, and early tumor stages were independent positive prognostic factors at multivariate analysis for 5-year overall survival. Abdominal complications and advanced tumor stages negatively influenced 5-year disease-free survival at multivariate analysis.

Conclusion: BII provides excellent results in terms of short and long-term prognosis and should be regarded as an acceptable reconstructive option following DG for GC.
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http://dx.doi.org/10.1016/j.amjsurg.2019.03.009DOI Listing
November 2019

Open versus minimally invasive surgery for rectal cancer: a single-center cohort study on 237 consecutive patients.

Updates Surg 2019 Sep 13;71(3):493-504. Epub 2019 Mar 13.

Digestive Surgery Unit of the Fondazione Policlinico "A.Gemelli", Catholic University of Sacred Heart, Largo Agostino Gemelli 8, 00166, Rome, Italy.

Minimally invasive surgery (MIS) is gaining popularity in rectal tumor treatment. However, contrasting data are available regarding its safety and efficacy. Our aim is to compare the open and MIS approaches for rectal cancer treatment. Two-hundred-thirty-seven patients were included: 113 open and 124 MIS rectal resections. After the propensity score matching analysis (PS), the cases were matched into 42 open and 42 MIS. Short- and long-term outcomes, and pathological findings were analyzed before and after PS. A further comparison of the same outcomes and costs was conducted between the laparoscopic and the robotic approaches. As a whole, a sphincter-preserving procedure was more frequently performed in the MIS group (110 vs 75 cases; p < 0.0001). The estimated blood loss during MIS was significantly lower than during open surgery [127 (± 92) vs 242 (± 122) mL; p < 0.0001], with clear advantages for the robotic approach over laparoscopy [113 (± 87) vs 147 (± 93) mL; p 0.01]. Complication rate was comparable between the two groups. A higher rate of CRM positivity was evidenced after open surgery (12.4% vs 1.7%; p 0.004). A higher number of lymph nodes was harvested in the MIS group [12.5 (± 6.4) vs 11 (± 5.6); p 0.04]. After PS, no difference in terms of perioperative outcomes was noted, with the only exception of a higher blood loss in the open approach [242 (± 122) vs 127 (± 92) mL; p < 0.0001]. For the matched cases, no difference in 5-year overall and disease-free survival was evidenced (p 0.50 and 0.88, respectively). Mean costs were higher for robotics as compared to laparoscopy [9812 (±1974)€ vs 9045 (± 1893)€; p 0.02]. MIS could be considered as a treatment option for rectal cancer. The PS study evidenced clear advantages in terms of estimated blood loss over the open surgery. Costs still remain the main limit for robotics.
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http://dx.doi.org/10.1007/s13304-019-00642-3DOI Listing
September 2019

Preferential MGMT methylation could predispose a subset of KIT/PDGFRA-WT GISTs, including SDH-deficient ones, to respond to alkylating agents.

Clin Epigenetics 2019 01 7;11(1). Epub 2019 Jan 7.

Department of Pathology, Università Cattolica del Sacro Cuore, Largo F.Vito 1, 00168, Rome, Italy.

Background: Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) constitute a small KIT/PDGFRA-WT GIST subgroup featuring DNA methylation which, although pervasive, appears nevertheless not randomly distributed. Although often indolent, these tumors are mostly chemorefractory in aggressive cases. Promoter methylation-induced O-methylguanine DNA methyltransferase (MGMT) inactivation improves the efficacy of alkylating agents in gliomas, colorectal cancer and diffuse large B cell lymphoma. MGMT methylation has been found in some GISTs, without determining SDH status. Thirty-six GISTs were enrolled in past sarcoma trials testing alkylating agents, with negative results. Nevertheless, a possible effect on MGMT-methylated GISTs could have escaped detection, since tested GISTs were neither selected by genotype nor investigated for SDH; MGMT was studied in two cases only, revealing baseline activity; these trials were performed prior to the adoption of Choi criteria, the most sensitive for detecting GIST responses to therapy. Under these circumstances, we investigated whether MGMT methylation is preferentially found in SDH-deficient cases (identified by SDHB immunohistochemistry) by analyzing 48 pathogenetically heterogeneous GISTs by methylation-specific PCR, as a premise for possible investigations on the use of alkylating drugs in these tumors.

Results: Nine GISTs of our series were SDH-deficient, revealing significantly enriched in MGMT-methylated cases (6/9-67%-, vs. 6/39-15%- of SDH-proficient GISTs; p = 0.004). The pathogenetically heterogeneous KIT/PDGFRA-WT GISTs were also significantly MGMT-methylated (11/24-46%-, vs. 1/24-4%- of KIT/PDGFRA-mutant cases, p = 0.002).

Conclusions: A subset of KIT/PDGFRA-WT GISTs, including their largest pathogenetically characterized subgroup (i.e., SDH-deficient ones), is preferentially MGMT-methylated. This finding could foster a reappraisal of alkylating agents for treating malignant cases occurring among these overall chemorefractory tumors.
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http://dx.doi.org/10.1186/s13148-018-0594-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322231PMC
January 2019
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