Pancreatic ductal adenocarcinoma: the latest on diagnosis, molecular profiling, and systemic treatments.

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.

Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening.

Pancreatic cancer (PC) is a highly malignant and aggressive tumor. Despite medical advancement, the silent nature of PC results in only 20% of all cases considered resectable at the time of diagnosis. It is projected to become the second leading cause in 2030. Most pancreatic cancer cases are diagnosed in the advanced stages. Such cases are typically unresectable and are associated with a 5-year survival of less than 10%. Although there is no guideline consensus regarding recommendations for screening for pancreatic cancer, early detection has been associated with better outcomes. In addition to continued utilization of imaging and conventional tumor markers, clinicians should be aware of novel testing modalities that may be effective for early detection of pancreatic cancer in individuals with high-risk factors. The pathogenesis of PC is not well understood; however, various modifiable and non-modifiable factors have been implicated in pancreatic oncogenesis. PC detection in the earlier stages is associated with better outcomes; nevertheless, most oncological societies do not recommend universal screening as it may result in a high false-positive rate. Therefore, targeted screening for high-risk individuals represents a reasonable option. In this review, we aimed to summarize the pathogenesis, genetic risk factors, high-risk population, and screening modalities for PC.

Gemcitabine and Cisplatin as Neo-Adjuvant for Cholangiocarcinoma Patients Prior to Liver Transplantation: Case-Series.

BACKGROUND: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. METHODS: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. RESULTS: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02-71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120-250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813-967). Overall survival was 100% (95% CI 100-100%) at both years one and two; 75% (95% CI 13-96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. CONCLUSIONS: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.