Catalina Mosquera

Molecular targeted therapy for pancreatic adenocarcinoma: A review of completed and ongoing late phase clinical trials

Molecular targeted therapy is widely utilized and effective in a number of solid tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The purpose of this study is to review therapeutic molecular targets in completed and ongoing later phase (II and III) clinical trials to have a better understanding of the rationale and progress towards targeted molecular therapies for pancreatic cancer. The PubMed database and the NCDI clinical trial website (www.clinicaltrials.gov) were queried to identify phase II and III completed and published (PubMed) and ongoing (clinicaltrials.gov) trials using the keywords: pancreatic cancer and molecular targeted therapy. The search engines were further limited by adding Phase II or III, active enrollment and North American. A total of 14 completed and published phase II/III clinical trials and 17 ongoing trials were identified. Evaluated strategies included inhibition of growth factor receptors (EGFR, PDGFR, VGFR, IGF-1R), tyrosine kinase inhibitors, MEK1/2, mTOR blockade and PI3K and HER2-neu pathway inhibitors. Only one trial conducted by the National Cancer Institute of Canada and the PANTAR trial have demonstrated a survival improvement from EGFR inhibition using erlotinib. These trials ultimately led to FDA approval of erlotinib/Tarceva in advanced stage disease. It remains unclear whether new combinations of cytotoxic chemotherapy or immunotherapy plus molecular targeted therapy will be beneficial in management of pancreatic adenocarcinoma. Despite a number of phase II and III trials, to date, only erlotinib has emerged as an approved targeted therapy in pancreatic adenocarcinoma. There are several ongoing late phase trials evaluating a number of targets, the results of which will become available over the next 1 to 2 years.

Perioperative chemotherapy versus postoperative chemoradiotherapy in patients with resectable gastric/gastroesophageal junction adenocarcinomas: A survival analysis of 5058 patients: PECT Versus POCRT

Both perioperative chemotherapy (PECT) and postoperative chemoradiotherapy (POCRT) have a significant survival advantage over surgery alone for the treatment of patients with gastric cancer. However, to the best of our knowledge, these regimens have not been compared in a randomized clinical trial. The purpose of the current observational study was to compare overall survival among patients receiving PECT versus POCRT for the treatment of gastric/gastroesophageal junction (GEJ) adenocarcinomas.

Novel nomogram combining depth of invasion and size can accurately predict the risk for regional nodal metastases for appendiceal neuroendocrine tumors (A-NET)

The need for regional lymphadenectomy for treating appendiceal neuroendocrine tumors (A‐NET) is determined by the risk of nodal metastasis. Current guidelines for A‐NET are solely based on tumor size.

Impact of frailty on approach to colonic resection: Laparoscopy vs open surgery

AIM To understand the influence of frailty on postoperative outcomes for laparoscopic and open colectomy. METHODS Data were obtained from the National Surgical Quality Improvement Program (2005-2012) for patients undergoing colon resection [open colectomy (OC) and laparoscopic colectomy (LC)]. Patients were classified as non-frail (0 points), low frailty (1 point), moderate frailty (2 points), and severe frailty (≥ 3) using the Modified Frailty Index. 30-d mortality and complications were used as the primary end point and analyzed for the overall population. Complications were grouped into major and minor. Subset analysis was performed for patients undergoing colectomy (total colectomy, partial colectomy and sigmoid colectomy) and separately for patients undergoing rectal surgery (abdominoperineal resection, low anterior resection, and proctocolectomy). We analyzed the data using SAS Platform JMP Pro version 10.0.0 (SAS Institute Inc., Cary, NC, United States). RESULTS A total of 94811 patients were identified; the majority underwent OC (58.7%), were white (76.9%), and non-frail (44.8%). The median age was 61.3 years. Prolonged length of stay (LOS) occurred in 4.7%, and 30-d mortality was 2.28%. Patients undergoing OC were older (61.89 ± 15.31 vs 60.55 ± 14.93) and had a higher ASA score (48.3% ASA3 vs 57.7% ASA2 in the LC group) (P < 0.0001). Most patients were non-frail (42.5% OC vs 48% LC, P < 0.0001). Complications, prolonged LOS, and mortality were significantly more common in patients undergoing OC (P < 0.0001). OC had a higher risk of death and complications compared to LC for all frailty scores (non-frail: OR = 4.7, and OR = 4.67; mildly frail: OR = 2.51, and OR = 2.47; moderately frail: OR = 2.94, and OR = 2.02, severely frail: OR = 2.37, and OR = 2.34, P < 0.05) and an increase in absolute mortality with increasing frailty (non-frail 0.68% OC, mildly frail 1.39%, moderately frail 3.44%, and severely frail 5.83%, P < 0.0001). CONCLUSION LC is associated with improved outcomes. Although the odds of mortality are higher in non-frail, there is a progressive increase in mortality with increasing frailty.

Enhanced Recovery after Surgery in a Single High-Volume Surgical Oncology Unit: Details Matter

Benefits of ERAS protocol have been well documented; however, it is unclear whether the improvement stems from the protocol or shifts in expectations. Interdisciplinary educational seminars were conducted for all health professionals. However, one test surgeon adopted the protocol. 394 patients undergoing elective abdominal surgery from June 2013 to April 2015 with a median age of 63 years were included. The implementation of ERAS protocol resulted in a decrease in the length of stay (LOS) and mortality, whereas the difference in cost was found to be insignificant. For the test surgeon, ERAS was associated with decreased LOS, cost, and mortality. For the control providers, the LOS, cost, mortality, readmission rates, and complications remained similar both before and after the implementation of ERAS. An ERAS protocol on the single high-volume surgical unit decreased the cost, LOS, and mortality.

Operative Techniques for Melanoma

This chapter will focus on the various operative techniques for biopsy and excision of cutaneous melanoma as well as the assessment and dissection of regional lymph node basins. The technique of performing a shave, punch, and incisional biopsy is reviewed, along with the advantages and disadvantages of each approach. This is followed by a discussion about standard recommendations regarding margins for wide excision and how to approach a wide excision of a melanoma in difficult areas like the nail beds, digits, and the heel. Common reconstructive techniques for tissue defects such as local tissue advancement and rhomboid flaps, as well as VY flaps, are described. Finally, complete lymph node dissection techniques are described in detail for the axillary, inguinal, and cervical lymph node basins.

Sentinel Lymph Node Biopsy for Melanoma

Intraoperative lymphatic mapping and selective sentinel lymphadenectomy (ILM and SLND) has dramatically altered the surgical management of the regional lymphatics in cutaneous melanoma. Once considered a standard component in the surgical management of patients with cutaneous melanoma, immediate complete lymph node dissection (CLND) or elective lymph node dissection (ELND) is now infrequently performed. Now commonly referred to as “sentinel lymph node biopsy,” ILM and SLND is an operative technique that was developed in order to identify patients with cutaneous melanoma who might benefit from the early detection and surgical management of metastatic disease in the regional lymph nodes while avoiding the significant morbidity of CLND in individuals without regional lymph node metastases and who had little likelihood of benefit from that procedure.