Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer.

BACKGROUND: New therapies are needed for pancreatic cancer. OBJECTIVE: To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. DESIGN: A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. SETTING: San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. PATIENTS: A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. INTERVENTION: Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. MAIN OUTCOME MEASUREMENTS: Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. RESULTS: The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). LIMITATIONS: Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. CONCLUSION: EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Transarterial chemoembolization with drug-eluting beads preloaded with irinotecan as a first-line approach in uveal melanoma liver metastases: tumor response and predictive value of diffusion-weighted MR imaging in five patients.

Five patients with uveal melanoma metastatic to the liver (two to five lesions per patient) were prospectively enrolled and treated with transarterial chemoembolization with drug-eluting beads preloaded with irinotecan as a first-line therapy. An overall response rate of 80% was obtained per Response Evaluation Criteria In Solid Tumors. All patients were alive after mean follow-up durations of 10.6 months and 16.3 months, respectively, after the first treatment and the diagnosis of liver metastasis. The apparent diffusion coefficient values obtained by diffusion-weighted magnetic resonance imaging were significantly lower in lesions that showed a response. These findings are very promising and can constitute the background for further studies involving larger cohorts of patients.

Body composition as a predictor of chemotherapy-related toxicity in pancreatic cancer patients: A systematic review.

Objectives: The objective of this systematic review was to assess associations between quantitative body composition measures extracted from imaging examinations and chemotherapy-related toxicity in pancreatic cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across included studies. Methods: This systematic review was conducted according to the PRISMA statement. A comprehensive literature search of three electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study; population characteristics; technical; body composition features evaluated; CA 19.9 tumor marker levels; chemotherapy drugs administered; toxicities (hematologic, nausea/vomiting, diarrhea, neuropathy, reduction of number of cycles, overall toxicity); association of body composition values with toxicities. The overall quality of the included studies was critically evaluated. Results: After the initial retrieval of 1137 articles, the systematic review included 12 articles (1/12 in the neo-adjuvant setting; 2/12 in the adjuvant setting; 3/12 in the metastatic setting; 2/12 in the unresectable setting; the other 4/12 included more than one clinical setting). The number of patients included ranged between 17 and 251; mean/median age ranged between 63 and 77 years; the percentage of sarcopenic patients ranged between 23 and 76%. The most frequent body composition parameter evaluated was skeletal muscle index (11/12). Chemotherapy regimens included gemcitabine (as monotherapy or in combination with other drugs); FOLFIRINOX and S-1. Among the trials including gemcitabine, 2/9 demonstrated an association with toxicity, whereas 7/9 did not; among those including FOLFIRINOX, one demonstrated associated toxicity whereas the others did not. Altogether, 4/12 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities. Conclusions: There is a wide variability of results about the association of body composition and chemotherapy-related toxicity in PC patients. Furthermore, cut-off values to define sarcopenia in PC patients are not yet uniformly defined. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier CRD42022337753.

18F-FDG PET Radiomics as Predictor of Treatment Response in Oesophageal Cancer: A Systematic Review and Meta-Analysis.

The best treatment strategy for oesophageal cancer patients achieving a complete clinical response after neoadjuvant chemoradiation is a burning topic. The available diagnostic tools, such as 18F-FDG PET/CT performed routinely, cannot accurately evaluate the presence or absence of the residual tumour. The emerging field of radiomics may encounter the critical challenge of personalised treatment. Radiomics is based on medical image analysis, executed by extracting information from many image features; it has been shown to provide valuable information for predicting treatment responses in oesophageal cancer. This systematic review with a meta-analysis aims to provide current evidence of 18F-FDG PET-based radiomics in predicting response treatments following neoadjuvant chemoradiotherapy in oesophageal cancer. A comprehensive literature review identified 1160 studies, of which five were finally included in the study. Our findings provided that pooled Area Under the Curve (AUC) of the five selected studies was relatively high at 0.821 (95% CI: 0.737-0.904) and not influenced by the sample size of the studies. Radiomics models exhibited a good performance in predicting pathological complete responses (pCRs). This review further strengthens the great potential of 18F-FDG PET-based radiomics to predict pCRs in oesophageal cancer patients who underwent neoadjuvant chemoradiotherapy. Additionally, our review imparts additional support to prospective studies on 18F-FDG PET radiomics for a tailored treatment strategy of oesophageal cancer patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021274636.

Contrast enhanced 4D-CT imaging for target volume definition in pancreatic ductal adenocarcinoma.

A procedure to improve target volume definition in pancreatic ductal adenocarcinoma by contrast enhanced 4D-CT imaging has been implemented for radiotherapy planning. The procedure allows good quality images to be obtained over the whole patient's breathing cycle in terms of anatomical details, pancreatic enhancement and vessel definition.

Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma.

PURPOSE: No standard salvage chemotherapy has been identified for metastatic pancreatic adenocarcinoma (mPA), and there is an urgent need for active agents against this disease. This phase II trial explored the activity of trabectedin in mPA progressing after gemcitabine-based first-line chemotherapy. METHODS: Patients with gemcitabine-resistant disease received trabectedin 1.3 mg/m(2) as a 3-h intravenous continuous infusion every 3 weeks until disease progression or unacceptable toxicity or for a maximum of 6 months. The primary endpoint was progression-free survival rate at 6 months (PFS-6). Since trabectedin modulates the production of selected inflammatory mediators, this study also aimed to identify inflammatory biomarkers predictive for response to trabectedin. RESULTS: Between February 2011 and February 2012, 25 patients received trabectedin. PFS-6 was 4%, median PFS 1.9 months (range 0.8-7.4), and median overall survival 5.2 months (range 1.1-24.3). Grade >2 toxicity consisted of neutropenia in 44% of patients, febrile neutropenia and thrombocytopenia both in 12%, anemia in 8%, fatigue in 12%, and AST and ALT increase in 8 and 4%, respectively. Trabectedin was shown to modulate the production of inflammatory mediators, and at disease progression, levels of a subgroup of cytokines/chemokines were modified. Furthermore, tissue analysis identified 30 genes associated with better prognosis. CONCLUSIONS: Although it has shown some ability to modulate inflammatory process, single-agent trabectedin had no activity as salvage therapy for mPA.

Interleukin-6 in ANCA-associated vasculitis: Rationale for successful treatment with tocilizumab.

OBJECTIVE: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are systemic, necrotizing, small-vessel vasculitis associated with circulating anti-neutrophil cytoplasmic autoantibodies (ANCA), and thus called ANCA-associated vasculitides (AAV). The aim of the present study is to evaluate a potential role of interleukin (IL)-6 and its pathway in the pathogenesis of AAV and to review previous evidence of IL-6 in MPA and GPA. METHODS: Blood and histological samples from 10 untreated myeloperoxidase (MPO)-ANCA/proteinase 3 (PR3)-ANCA-positive patients with active AAV were studied. Serum levels of cytokines/chemokines were evaluated by means of a Bio-Plex Multiple Cytokine Assay. IL-6 production at sites of active vasculitis was assessed by means of both immunohistochemistry and in situ hybridization techniques. We also treated a patient with MPA who was resistant or allergic to conventional treatments with a 12-month course of the IL-6 inhibitor tocilizumab and followed him up for 24 additional months. We also reviewed all the published cases in the English literature of histologically confirmed MPA or GPA, in which elevated IL-6 serum levels or intralesional IL-6 expression were reported. RESULTS: IL-6 serum levels were significantly increased in patients with AAV as compared to controls (median = 51.96pg/mL; range: 34.11-84.30; versus 0.68pg/mL; range: 0.01-1.81; P < 0.005). Also, IL-6 was expressed and produced at sites of active vasculitis. Treatment with tocilizumab was able to induce a complete and sustained disease remission in a patient with severe multisystemic MPA, as well as normalization of circulating levels of IL-6-associated pro-inflammatory cytokines and chemokines. Previous evidence of IL-6 pathway activation in AAV is scarce. Increased serum levels of IL-6 were reported in seven clinical studies for a total of approximately 120 patients, mainly affected by GPA. CONCLUSION: The finding of an activated IL-6 pathway in patients with AAV, together with the observed effects of tocilizumab monotherapy, provides evidence for a possible central role of IL-6 in the pathogenesis of AAV and suggests its targeting as a potential treatment.

[Intra-arterial thrombolysis facilitated by ultrasound in submassive pulmonary embolism: first documented case report in Italy]. / Trombolisi intra-arteriosa associata ad ultrasuoni nell'embolia polmonare submassiva: primo caso italiano.

A 76-year-old woman presented with a one-week history of dyspnea on minimal exertion and at rest. In the emergency room she underwent echocardiography and thoracic computed tomography scan with diagnosis of bilateral pulmonary embolism. Due to right ventricular dilatation and increasing values of NT-probrain natriuretic peptide, both markers of high risk that classify pulmonary embolism as "submassive" according to current international guidelines, we opted for thrombolysis. The patient underwent intra-arterial bilateral pulmonary thrombolysis facilitated by ultrasound, the first case in Italy. The patient recovered from pulmonary embolism after 10h of therapy, with improved gas exchange and symptoms. Subsequently, she developed arterial bleeding at the puncture site, due to accidental puncture of a branch of the femoral artery. The patient was treated with percutaneous embolization and transfusions. In patients with pulmonary embolism, even if not massive, thrombolysis should be considered, especially in the presence of high-risk markers. Direct intra-arterial pulmonary thrombolysis, facilitated by ultrasound, is an effective procedure that provides an alternative to conventional thrombolysis with the advantage of a lower thrombolytic dose.

A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen).

PURPOSE: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). METHODS: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and ß = 0.10; the study was to enroll 52 patients per arm. RESULTS: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. CONCLUSIONS: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.