VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer. METHODS: VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1×1011 viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography. RESULTS: VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption. CONCLUSIONS: VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma. TRIAL REGISTRATION NUMBER: EudraCT number: 2012-005556-42 and NCT02045589.

Hemostatic spray powder TC-325 for GI bleeding in a nationwide study: survival and predictors of failure via competing risks analysis.

BACKGROUND AND AIMS: TC-325 (Hemospray, Cook Medical, Winston-Salem, NC) is an inorganic hemostatic powder recently approved by the U.S. Food and Drug Administration. This study aimed to examine the effectiveness, safety, and predictors of TC-325 failure in a large real-life cohort. METHODS: This was a retrospective study conducted at 21 Spanish centers. All patients treated with TC-325 until September 2018 were included. The primary outcome was treatment failure, defined as failed intraprocedural hemostasis or recurrent bleeding within the first 30 postprocedural days. Secondary outcomes included safety and survival. Risk and predictors of failure were assessed via competing-risk models. RESULTS: The cohort comprised 261 patients, of whom 219 (83.9%) presented with upper gastrointestinal bleeding (GIB). The most common causes were peptic ulcer (28%), malignancy (18.4%), and therapeutic endoscopy-related GIB (17.6%). TC-325 was used as rescue therapy in 191 (73.2%) patients. The rate of intraprocedural hemostasis was 93.5% (95% confidence interval [CI], 90%-96%). Risks of TC-325 failure at postprocedural days 3, 7, and 30 were 21.1%, 24.6%, and 27.4%, respectively. On multivariate analysis, spurting bleeding (P = .004), use of vasoactive drugs (P = .02), and hypotension (P = .008) were independent predictors of failure. Overall 30-day survival was 81.9% (95% CI, 76%-86%) and intraprocedural hemostasis was associated with a better prognosis (adjusted hazard ratio, 0.29; P = .006). Two severe adverse events were noted. CONCLUSION: TC-325 was safe and effective for intraprocedural hemostasis in more than 90% of patients, regardless of the cause or site of bleeding and its use as rescue therapy. In this high-risk cohort treated with TC-325, the 30-day failure rate exceeded 25% and was highest with spurting bleeding or hemodynamic instability.

Endoscopic ultrasound-guided fiducial placement in pancreatic tumors: safety and technical feasibility

Background and aims: stereotactic body radiation therapy (SBRT) for pancreatic malignancies requires the placement of fiducials to guide treatment delivery. The aim of this study was to assess the safety and feasibility of endoscopic ultrasound (EUS) guided fiducial placement using a 22-gauge needle, in patients with pancreatic cancer undergoing SBRT. Methods: this single-center retrospective study included 47 patients with biopsy-proven advanced pancreatic cancer who underwent EUS-guided fiducial placement between February 2014 and February 2018. Primary outcome measurements included technical success, fiducial migration rate and procedural complications. Results: all 47 patients received a sufficient number of fiducials and could therefore undergo a successful SBRT. The mean number of fiducials inserted per case was 2 +/- 1 (range 1-3) and no fiducial migration was noted. The adverse event rate was 4.2%, as one patient developed mild pancreatitis and another patient required one week of hospitalization one month after fiducial placement due to a duodenal abscess. Conclusions: EUS-guided fiducial placement is a safe and technically feasible procedure in centers with endosonographers that are well trained in EUS with FNA

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Endoscopic ultrasound-guided fiducial placement in pancreatic tumors: safety and technical feasibility.

BACKGROUND AND AIMS: stereotactic body radiation therapy (SBRT) for pancreatic malignancies requires the placement of fiducials to guide treatment delivery. The aim of this study was to assess the safety and feasibility of endoscopic ultrasound (EUS) guided fiducial placement using a 22-gauge needle, in patients with pancreatic cancer undergoing SBRT. METHODS: this single-center retrospective study included 47 patients with biopsy-proven advanced pancreatic cancer who underwent EUS-guided fiducial placement between February 2014 and February 2018. Primary outcome measurements included technical success, fiducial migration rate and procedural complications. RESULTS: all 47 patients received a sufficient number of fiducials and could therefore undergo a successful SBRT. The mean number of fiducials inserted per case was 2 ± 1 (range 1-3) and no fiducial migration was noted. The adverse event rate was 4.2%, as one patient developed mild pancreatitis and another patient required one week of hospitalization one month after fiducial placement due to a duodenal abscess. CONCLUSIONS: EUS-guided fiducial placement is a safe and technically feasible procedure in centers with endosonographers that are well trained in EUS with FNA.

First Case of ROLL Technique for Mesorectal Recurrence Excision.

The radio-guided occult lesion localization (ROLL) technique has been in use since the mid-1990s, mainly in breast surgery. Today, ROLL is used for numerous oncologic pathologies, including parathyroid lesions, melanomas, and colorectal tumors. We report a patient with an 11-mm left mesorectal solitary recurrence of a primary ovarian cancer in whom the ROLL technique was used to identify the implant. A radioisotope was introduced through a 22-gauge needle with endoscopic ultrasound technique using an linear echo endoscope. On the day of surgery, the patient's perianal region was scanned with a gamma probe to identify the area of maximal radioactivity, to determine the optimal placement of the incision over the lesion. After macroscopic excision of the lesion, radioactivity was measured in the lesion bed to ensure complete removal of affected tissues. In our case, the ROLL technique was performed safely for the detection and excision of a recurrent lesion of difficult identification. To our knowledge, this is the first reported case involving use of the ROLL technique to aid the excision of a mesorectal lesion.

A prospective pilot study of target-guided personalized chemotherapy with intensity-modulated radiotherapy in patients with early rectal cancer.

PURPOSE: To investigate the feasibility of personalizing chemotherapy in patients with rectal cancer. METHODS: Patients with cT3 or cN1 and cM0 rectal cancer were eligible. A set of 6 molecular markers including KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), ERCC-1, and thymidylate synthase (TS) using immunohistochemistry were performed in a tumor biopsy. All patients were treated with capecitabine 625 to 825 mg/m/12 h M-F in combination with either irinotecan or oxaliplatin based on Topo-1 and ERCC-1 expression plus either bevacizumab or cetuximab based on the mutation status. All patients received intensity-modulated radiation therapy. A surgery was performed 6 to 8 weeks after the treatment. RESULTS: Fifteen patients (94%) had T3 tumor and 10 (62%) N+ disease of 16 patients enrolled. In all patients, the full set of markers was analyzed within 10 days. Seven patients had K-ras mutation, and 4, 5, and 10 expressed Topo-1, ERRC-1 and TS, respectively. All patients had wild-type BRAF and PI3K tumors. The median time from obtaining informed consent to the treatment period was 18 days and all patients completed the chemoradiation treatment. Fifty percent achieved a complete pathologic response to treatment. Four patients (25%) developed grade 3 proctitis or diarrhea. There were no relevant surgical complications. Sixty-nine percent of the patients received adjuvant XELOX. CONCLUSIONS: The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response.

BioEnterics® intragastric balloon (BIB®). Single ambulatory center Spanish experience with 714 consecutive patients treated with one or two consecutive balloons.

BACKGROUND: The BioEnterics® Intragastric Balloon (BIB®) is a well-established device for temporary treatment in morbidly obese patients. The aim of this study is the evaluation, in a population of 714 consecutive outpatient setting cases, BIB® results in terms of weight loss and comorbidity change. METHODS: BIB® was positioned in all cases after diagnostic endoscopy. The device was inflated under direct endoscopic vision with saline solution (600-700 ml) and methylene blue (10 ml). Intubation was carried out in patients with body mass index (BMI) > 40 kg/m(2) affected by sleep apnea or chronic obstructive pulmonary disease. After 6 months, balloon removal was carried out, and patients were discharged with drug therapy and 1,000 kcal diet. More than 100 patients underwent a second consecutive balloon positioning. One month from the removal of the first BIB, patients were given a second BIB. Patients were followed up weekly. Mortality, complications and their treatment, postplacement symptoms, comorbidities, BMI, percentage of excess BMI loss (%EBL), and percentage of excess weight loss (%EWL) were considered. Data are expressed as mean ± standard deviation. RESULTS: From June 1, 2005, to May 31, 2007, 714 patients underwent BIB® placement (143 males/571 females; mean age, 38.4 ± 16.1; mean BMI, 37.6 ± 5.7 kg/m(2); mean EW, 56.3 ± 27.1 kg). After 6 months, mean BMI was 31.1 ± 7.2, mean %EWL was 41.6 ± 21.8, mean BMI loss was 6.5 ± 12.7, and mean %EBL was 44.5 ± 22.6. Of 714 patients, 112 underwent a second BIB placement. At the time of the second balloon placement, mean BMI was 32.9 ± 6.7 kg/m(2); range was 31-51. After the second balloon removal, mean BMI was 30.3 ± 7.2. CONCLUSIONS: BIB® treatment is a safe and effective procedure for weight reduction, without mortality and with very low morbidity rates even in nonhospitalized patients. A second balloon can also be positioned without difficulties, achieving good results after 12 months of treatment.