Hepatic Artery Anomalies in Pancreaticoduodenectomy: Outcomes from a High-Volume Center.

INTRODUCTION: Hepatic artery anomalies (HAA) may have an impact on surgical and oncological outcomes of patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at our institution between July 2015 and January 2020 were retrospectively reviewed and classified into two groups: group 1, with presence of HAA, and group 2, with no HAA. A weighted logistic regression model was employed to assess the association between HAA and postoperative complications, and to assess the association between HAA and R status in patients with pancreatic cancer. RESULTS: 502 patients were considered for analysis, with 75 (15%) of them in group 1. They had either an accessory (n = 28, 40.8%) or replaced (n = 26, 36.6%) right hepatic artery. Most patients underwent surgery for a malignancy (n = 451; 90%); among them, vascular resection was performed in 69 cases (15%). The presence of a HAA was reported at preoperative imaging only in 4 cases (5%) and the aberrant vessel was preserved in 72% of patients. At weighted multivariable logistic regression analysis, HAA were not associated to higher odds of morbidity (odds ratio [OR]: 0.753, 95% confidence interval [CI]: 0.543-1.043) nor to R1 status in case of pancreatic cancer (OR: 1.583, 95% CI: 0.979-2.561). CONCLUSION: At our institution, the presence of HAA does not have an impact on postoperative outcomes or affects oncological clearance after PD. Hospitals', surgeons', volume and systematic review of preoperative imaging are all factors that help reduce possible adverse events.

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Prognostic Factors After Pancreatectomy for Pancreatic Cancer Initially Metastatic to the Liver.

BACKGROUND: Resection of initially oligometastatic pancreatic ductal adenocarcinoma (PDAC) following response to first-line chemotherapy is controversial. We herein updated a previous case series to investigate the oncologic outcomes and preoperative factors that could drive the decision-making process. METHODS: This retrospective analysis was limited to patients with liver-only synchronous metastases who experienced complete regression of the metastatic component and underwent pancreatectomy between October 2008 and July 2020 at two high-volume institutions. Clinical-pathologic variables were captured, and inflammation-based prognostic scores were calculated. Recurrence and survival analyses were performed using standard statistical methods. RESULTS: Overall, 52 patients were included. FOLFIRINOX was the most employed chemotherapy regimen (63.5%). Post-treatment tumor size, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly decreased relative to baseline evaluation. The median time from diagnosis to pancreatectomy was 10.2 months, while the median time from chemotherapy completion to pancreatectomy was 2 months. Major postoperative complications occurred in 26.9% of patients, while postoperative mortality was nil. The median disease-free survival (DFS) and overall survival (OS) from pancreatectomy were 16.5 and 23.0 months, respectively, and the median OS from diagnosis was 37.2 months. At multivariable analysis, vascular resection, operative time, prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were associated with OS. Operative time, platelet × neutrophil/lymphocyte count (SII), and PNI were associated with DFS. CONCLUSIONS: We confirm promising outcomes of selected patients who underwent pancreatectomy following downstaging of liver metastases. The absence of vascular involvement of the primary tumor, good nutritional status, and low inflammatory index scores could be useful to select candidates for resection.

401 consecutive minimally invasive distal pancreatectomies: lessons learned from 20 years of experience.

BACKGROUND: This study aimed to discuss and report the trend, outcomes, and learning curve effect after minimally invasive distal pancreatectomy (MIDP) at two high-volume centres. METHODS: Patients undergoing MIDP between January 1999 and December 2018 were retrospectively identified from prospectively maintained electronic databases. The entire cohort was divided into two groups constituting the "early" and "recent" phases. The learning curve effect was analyzed for laparoscopic (LDP) and robotic distal pancreatectomy (RDP). The follow-up was at least 2 years. RESULTS: The study population included 401 consecutive patients (LDP n = 300, RDP n = 101). Twelve surgeons performed MIDP during the study period. Although patients were more carefully selected in the early phase, in terms of median age (49 vs. 55 years, p = 0.026), ASA class higher than 2 (3% vs. 9%, p = 0.018), previous abdominal surgery (10% vs. 34%, p < 0.001), and pancreatic adenocarcinoma (PDAC) (7% vs. 15%, p = 0.017), the recent phase had similar perioperative outcomes. The increase of experience in LDP was inversely associated with the operative time (240 vs 210 min, p < 0.001), morbidity rate (56.5% vs. 40.1%, p = 0.005), intra-abdominal collection (28.3% vs. 17.3%, p = 0.023), and length of stay (8 vs. 7 days, p = 0.009). Median survival in the PDAC subgroup was 53 months. CONCLUSION: In the setting of high-volume centres, the surgical training of MIDP is associated with acceptable rates of morbidity. The learning curve can be largely achieved by several team members, improving outcomes over time. Whenever possible resection of PDAC guarantees adequate oncological results and survival.

A randomized controlled trial of stapled versus ultrasonic transection in distal pancreatectomy.

BACKGROUND: The pancreatic transection method during distal pancreatectomy is thought to influence postoperative fistula rates. Yet, the optimal technique for minimizing fistula occurrence is still unclear. The present randomized controlled trial compared stapled versus ultrasonic transection in elective distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy from July 2018 to July 2020 at two high-volume institutions were considered for inclusion. Exclusion criteria were contiguous organ resection and a parenchymal thickness > 17 mm on intraoperative ultrasound. Eligible patients were randomized in a 1:1 ratio to stapled transection (Endo GIA Reinforced Reload with Tri-Staple Technology®) or ultrasonic transection (Harmonic Focus® + or Harmonic Ace® + shears). The primary endpoint was postoperative pancreatic fistula. Secondary endpoints included overall complications, abdominal collections, and length of hospital stay. RESULTS: Overall, 72 patients were randomized in the stapled transection arm and 73 patients in the ultrasonic transection arm. Postoperative pancreatic fistula occurred in 23 patients (16%), with a comparable incidence between groups (12% in stapled transection versus 19% in ultrasonic dissection arm, p = 0.191). Overall complications did not differ substantially (35% in stapled transection versus 44% in ultrasonic transection arm, p = 0.170). There was an increased incidence of abdominal collections in the ultrasonic dissection group (32% versus 14%, p = 0.009), yet the need for percutaneous drain did not differ between randomization arms (p = 0.169). The median length of stay was 8 days in both groups (p = 0.880). Intraoperative blood transfusion was the only factor independently associated with postoperative pancreatic fistula on logistic regression analysis (OR 4.8, 95% CI 1.2-20.0, p = 0.032). CONCLUSION: The present randomized controlled trial of stapled versus ultrasonic transection in elective distal pancreatectomy demonstrated no significant difference in postoperative pancreatic fistula rates and no substantial clinical impact on other secondary endpoints.

US-Guided Percutaneous Radiofrequency Ablation of Locally Advanced Pancreatic Adenocarcinoma: A 5-Year High-Volume Center Experience.

PURPOSE: The aim of this study was to investigate the safety and effectiveness of percutaneous radiofrequency ablation (RFA) in locally advanced pancreatic cancer (LAPC) of the pancreatic body by assessing the overall survival of patients and evaluating the effects of the procedure in the clinical and radiological follow-up. MATERIALS AND METHODS: Patients with unresectable LAPC after failed chemoradiotherapy for at least six months were retrospectively included. Percutaneous RFA was performed after a preliminary ultrasound (US) feasibility evaluation. Contrast-enhanced computed tomography (CT) and CA 19.9 sampling were performed before and 24 hours and 30 days after the procedure to evaluate the effects of the ablation. Patients were followed-up after discharge considering the two main endpoints: procedure-related complications and death. RESULTS: 35 patients were included, 5 were excluded. All patients underwent RFA with no procedure-related complications reported. The mean size of tumors was 49 mm before treatment. The mean dimension of the ablated necrotic zone was 32 mm, with a mean extension of 65 % compared to the whole tumor size. Tumor density was statistically reduced one day after the procedure (p < 0.001). The mean CA 19.9 levels before and 24 hours and 30 days after the procedure were 285.8 U/mL, 635.2 U/mL, and 336.0 U/mL, respectively, with a decrease or stability at the 30-day evaluation in 80 % of cases. The mean survival was 310 (65-718) days. CONCLUSION: Percutaneous RFA of LAPC is a feasible technique in patients who cannot undergo surgery, with great debulking effects and a very low complication rate.

Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial.

BACKGROUND: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. METHODS: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. RESULTS: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). CONCLUSIONS: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients.

BACKGROUND: Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment. METHODS: This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments. Detected alterations were described according to ESMO Scale of Clinical Actionability for molecular Targets (ESCAT). RESULTS: NGS analysis was performed in 68 patients affected by PDC. At least one alteration ranking tier I, II, III, or IV according to ESCAT classification was detected in 8, 1, 9, and 12 patients respectively (44.1%). Ten of them (33.3%) received a matched therapy. Patients with ESCAT tier I to IV were generally younger than the overall population (median = 54, range = 26-71 years), had an EGOG performance status score = 0 (83.3%), and an uncommon histological or clinical presentation. The most common mutations with clinical evidence of actionability (ESCAT tier I-III) involved genes of the RAF (10.3%), BRCA (5.9%) or FGFR pathways (5.9%). We present the activity of the RAF kinases inhibitor sorafenib in patients with RAF-mutated advanced PDC. CONCLUSIONS: In advanced PDC, NGS is a feasible and valuable method for enabling precision oncology. This genomic profiling method might be considered after standard treatments failure, especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches.

Resectability of Pancreatic Cancer Is in the Eye of the Observer: A Multicenter, Blinded, Prospective Assessment of Interobserver Agreement on NCCN Resectability Status Criteria.

Objectives: To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background: The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods: Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed. Results: Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss' k range: 0.282-0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196-0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement. Conclusions: There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.

Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review.

The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138-0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.

Polyester sutures for pancreaticojejunostomy protect against postoperative pancreatic fistula: a case-control, risk-adjusted analysis.

BACKGROUND: There is wide variability in the use of suture material for pancreatic anastomosis after pancreaticoduodenectomy (PD). This study evaluates the role of suture material on clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticojejunostomy (PJ) in a risk-adjusted setting. METHODS: A retrospective study comparing (polyester) PE with polydioxanone (PDO) in 520 PDs. Patients were matched for risk for CR-POPF according to the fistula risk score (FRS) with the propensity score. RESULTS: The matched PE and PDO groups consisted of 232 patients. The incidence of CR-POPF was lower for PE group (11.6 vs. 22%, p<0.01), with a lower rate of grade B (10.3 vs. 15.5%, p<0.01) and C (1.3 vs. 6.5%, p<0.01). After stratifying by fistula risk zone, PE suture remained associated with a reduced incidence of CR-POPF (9.4 vs. 15.6% low-, p = 0.04; 15.6 vs. 28.1% intermediate-, p = 0.02; 16.7 vs. 83.3% high-risk zone, p<0.01, respectively). Multivariable analysis demonstrated that pancreatic texture, preoperative diagnosis, FRS and the use of PE sutures were independent predictors of CR-POPF. CONCLUSIONS: In the setting of a case-control matched for risk analysis, the use of PE suture for PJ is associated with a significant reduction of CR-POPF.

Technique, safety, and feasibility of EUS-guided radiofrequency ablation in unresectable pancreatic cancer.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is a well-recognized local ablative technique applied in the treatment of different solid tumors. Intraoperative RFA has been used for non-metastatic unresectable pancreatic ductal adenocarcinoma (PDAC), showing increased overall survival in retrospective studies. A novel RFA probe has recently been developed, allowing RFA under endoscopic ultrasound (EUS) guidance. Aim of the present study was to assess the feasibility and safety of EUS-guided RFA for unresectable PDACs. METHODS: Patients with unresectable non-metastatic PDAC were included in the study following neoadjuvant chemotherapy. EUS-guided RFA was performed using a novel monopolar 18-gauge electrode with a sharp conical 1 cm tip for energy delivery. Pre- and post-procedural clinical and radiological data were prospectively collected. RESULTS: Ten consecutive patients with unresectable PDAC were enrolled. The procedure was successful in all cases and no major adverse events were observed. A delineated hypodense ablated area within the tumor was observed at the 30-day CT scan in all cases. CONCLUSIONS: EUS-guided RFA is a feasible and safe minimally invasive procedure for patients with unresectable PDAC. Further studies are warranted to demonstrate the impact of EUS-guided RFA on disease progression and overall survival.

Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients.

PURPOSE: SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.

Immunomodulation after radiofrequency ablation of locally advanced pancreatic cancer by monitoring the immune response in 10 patients.

OBJECTIVE/BACKGROUND: RFA of pancreatic cancer has been demonstrated to be feasible and safe with a positive impact on survival. The aim was to investigate whether an immune reaction is activated after locally advanced pancreatic cancer (LAPC) ablation. METHODS: Peripheral Blood samples were obtained preoperatively and on post-operative days 3-30. Evaluated parameters were: cells [CD4+, CD8+ and activated subsets, T-Reg, Monocytes, myeloid and plasmocytoid Dendritic cells (mDC and pDC)] and cytokines [Interleukin (IL)-6, Stromal-cells derived factor (SDF)-1, IL-1ß, Tumour-Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Vascular Endothelial Growth Factor (VEGF), chemokine (C-C motif) ligand 5 (CCL-5), Transforming-Growth Factor (TGF)-ß]. RESULTS: Ten patients were enrolled. CD4+, CD8+ and TEM increased from day 3 suggesting the activation of the adaptive response. Immunosuppressive T-Reg cells were stable despite the possibility that laparotomy and heating might favour their expansion. Myeloid DCs, that present tumour-associated antigens, increased at day 30. RFA dramatically increased circulating IL-6 at day 3 but this decreased to baseline by day 30, consistent with the supposed anti-tumour effect. RFA did not significantly modulate essential chemokines, such as CCL-5 and SDF1, VEGF, TGF-ß and TNF-α, that favour tumour-growth by sustaining cancer angiogenesis and fuelling tumour-associated inflammation. CONCLUSIONS: This study provides the first evidence of RFA-based immunomodulation in LAPC. We observed a general activation of adaptive response along with a decrease of immunosuppression. Furthermore, most cells showed prolonged activation some weeks after the procedure, suggesting true immunomodulation rather than a normal inflammatory response.

Downstaging in Stage IV Pancreatic Cancer: A New Population Eligible for Surgery?

BACKGROUND: Recent papers consider surgery as an option for synchronous liver oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)]. In this study, we present our series of resected mPDACs after neoadjuvant chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: Overall, 24 of 535 patients (4.5%) observed with mPDAC were included. These patients received gemcitabine alone (5/24), gemcitabine + nanoparticle albumin-bound (nab)-paclitaxel (3/24), and FOLFIRINOX (16/24). Primary tumor size decreased from 31 to 19 mm (p < 0.001), and serum CA19-9 decreased from 596 to 18 U/mL (p < 0.001). In 14/24 patients, the tumor was located in the head. Median interval nCT surgery was 2 months, there were no mortalities, and the postoperative course was uneventful in 34% of cases. Grade B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4, and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was achieved in 88% of cases, with 17% complete pathological response. Positive nodes were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was 56 and 27 months, respectively. CONCLUSIONS: Patients with mPDAC who were fully responsive to nCT may be cautiously considered for surgery, with potential benefit in survival compared with palliative chemotherapy alone. This is supported by results of our retrospective study, which is the largest ever reported.

Pleural mesothelioma in doll manufacture: possible asbestos exposure. / Mesoteliomi pleurici in addette alla fabbricazione di bambole: esposizione ad amianto?

BACKGROUND: The occurrence of malignant mesothelioma is almost always causally associated to asbestos exposure but, considering women occurrences, this association is often difficult to demonstrate and consequently the asbestos exposure is defined as 'unknown'. OBJECTIVES: To describe the working activity and to give occupational asbestos exposure probability estimation related to an uncommon and poorly investigated productive sector: doll manufacture. METHODS: From the Province of Brescia Mesothelioma Registry, established in 1993 on population-based criteria, we have extracted the certified mesothelioma diagnosis cases, related to patients who were employed for some time in doll manufacture. RESULTS: Among the 757 total cases of malignant mesothelioma registered and studied up to 2016, we found 3 cases of pleural epithelial mesothelioma histologically diagnosed in young women who had worked in two doll manufacturing companies and whose asbestos exposure had been initially defined as 'unknown', because an environmental, family or extra-professional asbestos exposure was considered unlikely. However, the judicial autopsy performed on one of the 3 women had allowed examining lung tissue samples with Scanning Electron Microscopy. This technique showed a concentration of amphiboles fibers of about 12,000,000 per gram of dry lung tissue, with a consequent re-classification of asbestos exposure from 'unknown' to 'occupational certified'. DISCUSSION: Mesotheliomas in women with no apparent occupational asbestos exposure are normally referred to life or family environmental exposure. Moreover, it is known that occupational asbestos exposure in women is difficult to recognize. Previously, only one publication had reported two cases of mesothelioma in cloth doll manufacture. The occurrence of two mesothelioma cases in the same company out of the three here presented was suggesting an occupational exposure. The finding of a high amphibole fibers lung concentration confirmed the previous hypothesis, despite the impossibility to determine the circumstances with good evidence. CONCLUSION: The three cases of mesothelioma in doll production workers suggest that also in this restricted manufacturing sector had occurred an occupational asbestos exposure, which is up to now unknown and isn't due only to the use of sewing or ironing machines. The lung asbestos fibers burden analysis is confirmed to be a decisive factor in the assessment of mesothelioma cases with 'unknown' exposure.

Pancreatic neuroendocrine neoplasms: Magnetic resonance imaging features according to grade and stage.

AIM: To describe magnetic resonance (MR) imaging features of pancreatic neuroendocrine neoplasms (PanNENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior. METHODS: This study was approved by our institutional review board; requirement for informed patient consent was waived due to the retrospective nature of the study. Preoperative MR examinations of 55 PanNEN patients (29 men, 26 women; mean age of 57.6 years, range 21-83 years) performed between June 2013 and December 2015 were reviewed. Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis. RESULTS: Ill defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors (P < 0.001); this feature had high specificity in the identification of G2-3 and stage III-IV tumors (90.3% and 96%, 95%CI: 73.1-97.5 and 77.7-99.8). The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors (1.09 × 10-3 mm2/s vs 1.45 × 10-3 mm2/s and 1.10 × 10-3 mm2/s vs 1.53 × 10-3 mm2/s, P = 0.003 and 0.001). Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28 × 10-3 mm2/s for the identification of G2-3 and stage III-IV tumors, with sensitivity and specificity values of 70.8/80.7% and 64.5/64% (95%CI: 48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3). CONCLUSION: MR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.

Percutaneous ablation of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review.