Toufic Kachaamy

Promising new therapies in advanced pancreatic adenocarcinomas

Pancreatic ductal adenocarcinoma is a lethal disease due to late diagnosis, early metastasis and the lack of effective therapies. In patients with metastatic disease, 1-year survival ranges from 17 to 23% and 5-year survival is less than 5%. This necessitates an urgent need for developing more effective therapies. Targeting the neoplastic cells has been largely ineffective due to the dense stroma, which is a physical barrier for effective drug delivery and also a source for different factors that promote tumor progression and immunosuppression. In this review, we focus on understanding the complex biology of this tumor as it relates to the evaluation of previously failed molecularly targeted trials and review potential new therapies that are emerging in the treatment of metastatic pancreatic ductal adenocarcinoma.

Measures of patient radiation exposure during endoscopic retrograde cholangiography: Beyond fluoroscopy time

AIM To determine whether fluoroscope time is a good predictor of patient radiation exposure during endoscopic retrograde cholangiopancreatography. METHODS This is a prospective observational study of consecutive patients undergoing endoscopic retrograde cholangiopancreatography in a tertiary care setting. Data related to radiation exposure were collected. The following measures were obtained: Fluoroscopy time (FT), dose area product (DAP) and dose at reference point (DOSERP). Coefficients of determination were calculated to analyze the correlation between FT, DAP and DOSRP. Agreement between FT and DAP/DOSRP was assessed using Bland Altman plots. RESULTS Four hundred sixty-three data sets were obtained. Fluoroscopy time average was 7.3 min. Fluoroscopy related radiation accounted for 86% of the total DAP while acquisition films related radiation accounted for 14% of the DAP. For any given FT there are wide ranges of DAP and DOSERP and the variability in both increases as fluoroscopy time increases. The coefficient of determination (R(2)) on the non transformed data for DAP and DOSERP versus FT were respectively 0.416 and 0.554. While fluoroscopy use was the largest contributor to patient radiation exposure during endoscopic retrograde cholangiography (ERCP), there is a wide variability in DAP and DOSERP that is not accounted for by FT. DAP and DOSERP increase in variability as FT increases. This translates into poor accuracy of FT in predicting DAP and DOSERP at higher radiation doses. CONCLUSION DAP and DOSERP in addition to FT should be adopted as new ERCP quality measures to estimate patient radiation exposure.

A retrospective matched cohort study evaluating the effects of percutaneous endoscopic gastrostomy feeding tubes on nutritional status and survival in patients with advanced gastroesophageal malignancies undergoing systemic anti-cancer therapy

Background Many patients with cancer or other systemic illnesses can experience malnutrition. One way to mitigate malnutrition is by insertion of a percutaneous endoscopic gastrostomy feeding tube (PEG tube). The goal of this retrospective matched cohort study is to evaluate if PEG tube placement improved nutritional status and overall survival (OS) in advanced gastroesophageal (GE) cancer patients who are undergoing anti-neoplastic therapy. Methods GE cancer patients who were treated and evaluated by a nutritionist and had at least 2 nutritionist follow-up visits were identified. Patients with PEG tube were matched to patients that did not undergo PEG placement (non-PEG). Clinical characteristics, GE symptoms reported at nutrition follow-up visits, and OS were recorded. Results 20 PEG and 18 non-PEG cases met criteria for further analyses. After correction for multiple testing, there were no OS differences between PEG and non-PEG, treatment naive and previously treated. However, PEG esophageal carcinoma has statistically significant inferior OS compared with non-PEG esophageal carcinoma. PEG placement did not significantly reduce the proportion of patients with weight loss between the initial nutrition assessment and 12-week follow-up. Conclusions In this small study, PEG placement had inferior OS outcome for GE esophageal carcinoma, no improvement in OS for other evaluated groups, and did not reduce weight loss between baseline and 12-week follow-up. Unless there is prospective randomized trial that can show superiority of PEG placement in this population, PEG placement in this group cannot be endorsed.

Safety of endoscopy in cancer patients on antiangiogenic agents: A retrospective multicenter outcomes study

Background/Aims The use of antiangiogenic agents (AAs) in cancer treatment has increased because they offer survival benefit in combination with cytotoxic chemotherapy. Given their potential to cause gastrointestinal (GI) perforation and bleeding, it is currently recommended that AAs be held for 28 days before and after surgery. However, there are no specific guidelines which address their use around endoscopic procedures because data regarding the safety of endoscopy in cancer patients while on AAs is scarce despite the fact that these patients often require endoscopy. This study investigated the safety of endoscopy in cancer patients receiving AAs. Methods This is a retrospective multicenter study of a consecutive case series of 445 cancer patients undergoing endoscopy within 31 days of administration of AAs at 5 specialized cancer centers between April 2008 and August 2014. Endoscopies were classified into two different categories based on the risk of GI bleeding and perforation: low and high. The primary outcome measures were procedure-related adverse events (AEs) and death within 30 days of endoscopy. The severity of AEs was classified according to the common terminology criteria for adverse events (CTCAE) version 4.0. The incidence of AEs and mortality was calculated using the total number of patients as the denominator. Results 445 cancer patients with a mean age of 54 years underwent a total of 545 endoscopies. Median time duration from AAs to endoscopy was 11 days. Of 545 endoscopic procedures, 398 (73%) were low-risk and 147 (27%) were high-risk. There were 3 procedure-related AEs: esophageal perforation (grade 3) two days after an EGD, pancreatitis (grade 5) a day after failed ERCP, and bleeding from the gastrostomy site (grade 1) two days after an EGD. Of 445 patients, 29 (6.5%) died within 30 days of the procedure with no deaths deemed procedure-related. The most common causes of death were terminal cancer (n = 10), hepatic decompensation (n = 5) and sepsis (n = 4). Conclusion In this retrospective study, the rate of endoscopy-related AEs in patients on AAs appears to be low when performed in specialized cancer centers. However, future prospective studies are needed to confirm this finding.

Intraoperative laparoscopic-assisted pancreatoscopy and its role in differentiating main duct intraductal papillary mucinous neoplasm from chronic pancreatitis.

A 66-year-old patient with diabetes was seen after a 1-year history of steatorrhea and weight loss. He had no history of pancreatitis. The results of physical examination and laboratory tests, including carbohydrate antigen 19-9, were unrevealing. Magnetic resonance imaging showed a severely dilated pancreatic duct (PD) with a possible mural nodule. EUS showed a pancreatic stone and no mural nodule. The result of examination of a biopsy specimen from the PD obtained during endoscopic retrograde pancreatography was negative; however, pancreatic fluid carcinoembryonic antigen was 690 ng/mL. Pancreatoscopy with Spyglass (Boston Scientific, USA) was not successful. Given the conflicting data and the continued concern about a main duct intraductal papillary mucinous neoplasm (IPMN), the patient was offered total pancreatectomy with the option of a prior intraoperative pancreatoscopy in an attempt to rule out IPMN. During laparoscopy, a ductotomy was performed in the tail of the pancreas, through which an Olympus GIF-XP180N endoscope (Olympus, Japan) was advanced, allowing examination of the entire PD from the tail to the ampulla (Video 1, available online at www.giejournal.org). The PD mucosa was normal, with no evidence of papillary projections (Fig. 1A).