Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

Two Cases, Too Little, Too Late: Surveillance for Gastric Cancer in Patients with FAP.

Familial adenomatous polyposis is an autosomal dominant disease due to a mutation in the adenomatous polyposis coli (APC) gene. The disease, characterized by the development of adenomas throughout the colon and rectum, is also associated with extracolonic manifestations including gastric fundic polyps and cancer. In this report, we describe two patients with FAP with advanced gastric adenocarcinoma who received systemic chemotherapy. We reviewed the literature published over the past two decades on gastric cancer in FAP patients to assess the clinical course of this disease. Due to its recent increased incidence in Western countries, close endoscopic surveillance to detect early gastric neoplastic lesions is recommended.

Should EUS-FNA be considered also for the diagnosis of peripheral small pulmonary lesions?

Given the high rate of small lung nodules detected during the oncological follow up for various cancers, in the era of personalize medicine, the histological diagnosis is of paramount importance. Usually, the small peripheral lung nodules are historically reached using a CT guided biopsy but this technique is characterized by an high rate of pneumothorax. Endoscopic procedures were referred only for central tumor that occluded the mains bronchi. In the last few years, the spreading of EBUS-TBNA, EUS-FNA and the navigational bronchoscopy systems has increase the use of these technique also for the diagnosis of small lung nodules.

Transesophageal Endoscopic Ultrasound Fine Needle Biopsy for the Diagnosis of Mediastinal Masses: A Retrospective Real-World Analysis.

Background: Endoscopic ultrasound (EUS) plays an important role in the diagnosis and staging of thoracic disease. Our report studies the diagnostic performance and clinical impact of EUS fine needle aspiration (FNA) in a homogenous cohort of patients according to the distribution of the enlarged MLNs or pulmonary masses. Methods: We retrospectively reviewed the diagnostic performance of 211 EUS-FNA in 200 consecutive patients with enlarged or PET-positive MLNs and para-mediastinal masses who were referred to our oncological center between January 2019 and May 2020. Results: The overall sensitivity of EUS-FNA was 85% with a corresponding negative predictive value (NPV) of 56% and an accuracy of 87.5%. The sensitivity and accuracy in patients with abnormal MLNs were 81.1% and 84.4%, respectively. In those with para-mediastinal masses, sensitivity and accuracy were 96.4% and 96.8%. The accuracy for both masses and lymph nodes was 100%, and in the LAG (left adrenal gland), it was 66.6%. Conclusions: Our results show that, in patients with suspected mediastinal masses, EUS-FNA is an accurate technique to evaluate all reachable mediastinal nodal stations, including station 5.

Not enough can be enough: feasibility of the Idylla EGFR mutation test when reuse of stained tissue slides is the only option available.

AIMS: The minimally invasive procedures used in the diagnostic workup of patients with advanced non-small cell lung cancer (NSCLC) often provide poor yields of pathological material suitable for molecular analyses. Not infrequently, the DNA yield from small biopsies/cytological samples is insufficient for the assessment of genomic biomarkers that inform personalised therapies. The Idylla EGFR mutation test (IEMT) has been specifically designed to process formalin-fixed paraffin-embedded sections without requiring preliminary DNA extraction.This study aims to evaluate the diagnostic accuracy of IEMT when used to analyse archival histopathology material. More specifically, our objective was to establish whether or not different staining procedures could affect assay performance. METHODS: Twenty NSCLC samples were selected accordingly to EGFR mutational status. To mimic archived stained material, sections were subjected to H&E staining, fluorescent in situ hybridisation analyses or immunodetection by immunohistochemistry before being processed for IEMT. RESULTS: Parallel assessment of EGFR mutational status by IEMT on stained sections and next-generation sequencing on DNA yielded a concordant result in 50 out of 60 tests (83.3%). The discoloration of H&E of the archived sample was found to be the optimal procedure to highlight all the actionable alterations of EGFR. CONCLUSIONS: IEMT can provide remarkable diagnostic accuracy for the assessment of EGFR mutational status also when the only source of pathological material available for molecular analyses is represented by H&E stained sections. Ad hoc supervision by a qualified molecular biologist is in any case recommended.

Mediastinal lymph node metastasis as a single expression of disease relapse in Ewing's sarcoma: multidisciplinary approach of two consecutive cases.

Ewing's sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. Progress in the treatment of Ewing's sarcoma has improved survival from about 10%, before the introduction of chemotherapy, to about 75% today for patients with localized tumors. On the contrary, metastatic disease still has a poor prognosis, and a multidisciplinary approach is essential to improve the outcome. Molecular techniques and new imaging modalities are affecting the diagnosis and classification of patients with Ewing's sarcoma. The most frequent sites of metastases in Ewing's sarcoma include lungs, bones and bone marrow. Lymph nodes are a rare site of metastatic spread, particularly in the mediastinum. In this report, we present two consecutive cases of patients with Ewing's Sarcoma, diagnosed, and treated at our institute. We focused particularly on the rarity of the atypical presentation of the disease and on the synergistic strategy to adopt as a model of networking in treating patients with rare diseases.

Five years of thoracic endoscopy unit activity on lung cancer staging: how teamwork can improve the outcomes.

BACKGROUND: Regarding the staging of mediastinal lymph nodes before lung cancer surgery, Endobronchial Ultrasound Transbronchial Needle Aspirations (EBUS-TBNA) have proven to be highly sensitive and specific as well as safe. Endoscopic Ultrasound Fine Needle Aspirations (EUS-FNA) plays an important role in the diagnosis and staging of thoracic diseases, including lung cancer. In this study we analysed all patients underwent endoscopic procedures in our endoscopic mediastinal ultrasound unit. METHODS: Between January 2013 and February 2018, we performed a total of 929 endoscopic procedures, 432 EBUS-TBNA and 497 EUS-FNA. Biopsy was performed at the following mediastinal sites: station 7 in 642 cases, at stations 8 and 9 in 211 cases; at station 3P and 4L in 27 and 114 cases respectively; with EUS we were able to perform biopsy at station 5 in 52 cases. RESULTS: A total of 841 patients showed a diagnosis of cancer: non-small cell lung cancer (NSCLC) in 645 patients, SCLC in 190 patients, neuroendocrine tumour in 5 patients and one patient with mesothelioma. 88 patients were negative for cancer. In terms of sensitivity, specificity and accuracy, the association between EUS-FNAb and EBUS-TBNAb showed a better quality on diagnosis compared to single procedures. EUS-FNA and EBUS-TBNA are safe, feasible, and highly sensitive techniques. CONCLUSIONS: An endoscopic mediastinal ultrasound unit allows to perform a higher number of endoscopic procedures and improved the sensitivity and the accuracy of the minimally invasive hilar-mediastinal staging.

Tertiary stent-in-stent for obstructing colorectal cancer: A case report and literature review.

BACKGROUND: Self-expandable metal stents (SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer (CRC). Among possible complications of SEMS positioning, re-obstruction is the most frequent. Its management is controversial, potentially involving secondary stent-in-stent placement, which has been poorly investigated. Moreover, the issue of secondary stent-in-stent re-obstruction and of more-than-two colonic stenting has never been assessed. We describe a case of tertiary SEMS-in-SEMS placement, and also discuss our practice based on available literature. CASE SUMMARY: A 66-year-old male with occluding and metastatic CRC was initially treated by positioning of a SEMS, which had to be revised 6 mo later when a symptomatic intra-stent tumor ingrowth was treated by a SEMS-in-SEMS. We hereby describe an additional episode of intestinal occlusion due to recurrence of intra-stent tumor ingrowth. This patient, despite several negative prognostic factors (splenic flexure location of the tumor, carcinomatosis with ascites, subsequent chemotherapy that included bevacizumab and two previously positioned stents (1 SEMS and 1 SEMS-in-SEMS)) underwent successful management through the placement of a tertiary SEMS-in-SEMS, with immediate clinical benefit and no procedure-related adverse events after 150 d of post-procedural follow-up. This endoscopic management has permitted 27 mo of partial control of a metastatic disease without the need for chemotherapy discontinuation and, ultimately, a good quality of life until death. CONCLUSION: Tertiary SEMS-in-SEMS is technically feasible, and appears to be a safe and effective option in the case of recurrent SEMS obstruction.

Esophagojejunal anastomosis leakage after total gastrectomy for esophagogastric junction adenocarcinoma: options of treatment.

BACKGROUND: Esophagojejunal anastomosis leakage after total gastrectomy (TG) for esophagogastric junction (EGJ) adenocarcinoma (ADC) constitutes one of the most serious and sometimes life-threatening complications. Management remains controversial and still challenging. METHODS: A total of 198 patients operated for type I and II EGJ ADC were reviewed. Diagnosis of leakage was based on a combination of clinical and radiological findings. It was classified including objective endoscopic and clinical parameters requiring different type of treatment. RESULTS: Anastomotic leakage was diagnosed in 14 patients (7%). Two cases recovered with conservative therapy. Six cases underwent endoscopy with clips placement in 2 and partially covered self-expandable metal stent placement in 4. Other two cases underwent reoperation with reconstruction of anastomosis and primary repair respectively. In the last four cases emergency surgery with total esophagectomy and diversion was required. Mortality occurred only in 3 of these patients and overall treatment was successful in 11 patients (78.5%). CONCLUSIONS: No consensus has been reached on the best method of esophagojejunal anastomosis leakage management and the rate of failure remains significant. Different options of treatment are available but early detection and multidisciplinary approaches are the keys to obtain successful results irrespective of the employed strategy.

Endoscopic treatment of neoplastic enteral obstruction by means of self-expanding metal stents.

BACKGROUND: Neoplastic gastroduodenal inoperable stenosis require a palliative treatment to restore alimentary transit. OBJECTIVE: Our purpose was to treat neoplastic gastroduodenal stenosis with self-expanding enteral stents. MATERIAL OF STUDY: An endoscopic treatment with uncovered self-expanding metal stents has been performed in 45 patients: 37 duodenal stenosis (34 pancreatic neoplasia, 1 gallbladder neoplasia, 2 peritoneal carcinosis), 5 anthropyloric neoplastic stenosis and 3 gastro-jejunal anastomosis stenosis were treated. A total of 47 metal stent were positioned: in 43 patient 1 stent; in 2 patient, with a long stenosis, 2 stents. MAIN OUTCOME MEASUREMENT: Efficacy of endoscopic treatment to restore alimentary transit. RESULTS: The positioning was successfull in all cases without any complication. All patients had a rapid and satisfying recovery from symptoms connected to the obstruction. The hospitalization period was averagely 3 days (range 1-7). In one patient another stent was inserted 2 months later because of tunoral ingrowth. The median survival period was 4 months (range 1-5). In one patient with duodenal stenosis due to pancreatic neoplasia,in which were inserted 2 stents, distal one dislocated in the jejunum 3 months later. It was removed by surgery. CONCLUSIONS: The endoscopic stenting is a valid treatment of inoperable gastric duodenal stenosis and may become the preferable option for the palliative treatment of this pathology. KEY WORDS: Endoscopy, Gastroduodenal, Neoplasia, Obstruction, Stent.

Anti-Helicobacter pylori therapy in primary MALT lymphoma of rectum.

Primary rectal MALT lymphoma is a very rare entity among extranodal MALT lymphomas and its therapeutic management has not been standardized. Different approaches including surgery, chemotherapy and radiotherapy have been proposed in the last decades. There have been reports on complete responses after anti-Helicobacter pylori therapy, also in patients without serological or histological evidence of Helicobacter pylori infection. In our patient we obtained a complete response with anti-Helicobacter pylori therapy and a disease-free survival of 34 months. Endoscopic ultrasound was useful for diagnosis and follow-up. Although the mechanisms that determined this response remain a matter of debate, anti-Helicobacter pylori therapy can be considered as first-line therapy in stage IE, nonbulky primary rectal MALT lymphoma. Endoscopic ultrasound could play a relevant role in the management of this rare condition.

FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90Yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases.

BACKGROUND: This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. METHODS: The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m2x 3 days), C (1 gr/m2 day 1) and R (375 mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. RESULTS: Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. CONCLUSIONS: Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by 90Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS.

Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients.

BACKGROUND: Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients. METHODS: We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970-1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test. RESULTS: The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001). CONCLUSION: Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.

Cell surface overexpression of galectin-3 and the presence of its ligand 90k in the blood plasma as determinants in colon neoplastic lesions.

Galectins are a family of beta-galactoside binding molecules involved in cell--extracellular matrix adhesion processes. Specifically, Galectin-3 (Gal-3), one of the members of this family of molecules plays a role in cell adhesion processes as well as in cell survival or apoptosis. Gal-3 was also hypothesized to represent a useful tool in tumor characterization, for example, in thyroid tumors. We report herein the results obtained by evaluating Gal-3 expression of colon cells from human adenomas and adenocarcinomas with two different methodologies: immunohistochemistry and flow cytometry of living dispersed cells. We found that (1) the expression of Gal-3 was significantly increased on the surface of cells from adenomas with respect to normal mucosa from the same patient; (2) Gal-3 ligand, 90k molecule, was increased in the blood plasma from patients with both adenomatous and adenocarcinomatous lesions; and (3) Gal-3 overexpression was not related with the presence of K-ras mutation. Altogether these results clearly indicate that the evaluation of Gal-3 expression (and of its ligand, 90k) can be of interest in the characterization of nonmalignant and malignant colon cancers.