Challenges for cancer patients returning home during SARS-COV-19 pandemic after medical tourism - a consensus report by the emirates oncology task force.

BACKGROUND: The COVID-19 pandemic has caused a global health crisis. Numerous cancer patients from non-Western countries, including the United Arab Emirates (UAE), seek cancer care outside their home countries and many are sponsored by their governments for treatment. Many patients interrupted their cancer treatment abruptly and so returned to their home countries with unique challenges. In this review we will discuss practical challenges and recommendations for all cancer patients returning to their home countries from treatment abroad. METHOD: Experts from medical, surgical and other cancer subspecialties in the UAE were invited to form a taskforce to address challenges and propose recommendations for patients returning home from abroad after medical tourism during the SARS-COV-19 Pandemic. RESULTS: The taskforce which consisted of experts from medical oncology, hematology, surgical oncology, radiation oncology, pathology, radiology and palliative care summarized the current challenges and suggested a practical approaches to address these specific challenges to improve the returning cancer patients care. Lack of medical documentation, pathology specimens and radiology images are one of the major limitations on the continuation of the cancer care for returning patients. Difference in approaches and treatment recommendations between the existing treating oncologists abroad and receiving oncologists in the UAE regarding the optimal management which can be addressed by early and empathic communications with patients and by engaging the previous treating oncologists in treatment planning based on the available resources and expertise in the UAE. Interruption of curative radiotherapy (RT) schedules which can potentially increase risk of treatment failure has been a major challenge, RT dose-compensation calculation should be considered in these circumstances. CONCLUSION: The importance of a thorough clinical handover cannot be overstated and regulatory bodies are needed to prevent what can be considered unethical procedure towards returning cancer patients with lack of an effective handover. Clear communication is paramount to gain the trust of returning patients and their families. This pandemic may also serve as an opportunity to encourage patients to receive treatment locally in their home country. Future studies will be needed to address the steps to retain cancer patients in the UAE rather than seeking cancer treatment abroad.

Metastatic papillary gallbladder carcinoma with a unique presentation and clinical course.

CONTEXT: Papillary gallbladder adenocarcinoma (PGA) represents 5% of malignant gallbladder tumors. Metastatic disease frequently involves lymph nodes or other structures in the hepatoduodenal ligament. CASE REPORT: A Fifty-nine-year-old female with right upper quadrant pain and a giant gallbladder on ultrasound was found to have a segment 6 liver lesion during an attempted laparoscopic cholecystectomy. After appropriate staging, she underwent an open cholecystectomy and extended right hepatic lobectomy with portal lymph node dissection. Pathology demonstrated well-to-moderately differentiated PGA with identical morphology and immunohistochemistry in the liver resection specimen with negative margins. Despite adjuvant chemotherapy, she developed increased uptake in the head of the pancreas on PET scan. Endoscopic ultrasound with fine needle aspiration demonstrated metastatic PGA. She underwent an attempted Whipple operation but due to repeatedly positive pancreatic duct margins, she ended up with a total pancreatectomy and splenectomy. Final pathology showed metastatic PGA along the entire length of the pancreatic duct with only a single focus of tumor invasion into the pancreatic parenchyma. She developed a new liver metastases six months later that was unresponsive to FOLFOX therapy and she died of metastatic disease 33 months from her initial diagnosis. CONCLUSION: To our knowledge, this is the first report of metastatic PGA recurring along the entire pancreatic duct with disease confined to the pancreas only. We hypothesize that papillary tumor cells spread to pancreatic duct via the common bile duct and remained dormant for several years. An aggressive surgical approach may prolong survival in well-selected patients with PGA's.

Synchronous presentation of ampullary adenocarcinoma and common bile duct cancer: report of a case and review of literature.

CONTEXT: Ampullary adenocarcinomas and bile duct cancers represent a very small minority of all gastrointestinal malignancies. Synchronous presentation of both malignancies is extremely rare. CASE REPORT: We report a case of a 76-year-old male who presented with painless jaundice. His work-up showed an ampullary mass and a separate common bile duct stricture. Attempted endoscopic resection established the diagnosis of ampullary adenocarcinoma. Pathologic examination of the Whipple specimen identified a separate focus of bile duct cancer. CONCLUSION: Synchronous presentation of an ampullary mass and separate distal bile duct stricture, especially in elderly patients, should raise concern for both lesions representing malignancies. In the absence of conclusive evidence for survival advantage in resected early stage ampullary and biliary cancers, close observation should be considered a valid alternative to adjuvant chemotherapy and radiation.

Recurrent pancreatic adenocarcinoma after pancreatic resection.

The patient is a 57-year old Caucasian female who presented with right upper quadrant pain and obstructive jaundice and was diagnosed with resectable pancreatic cancer. She underwent pancreaticoduodenectomy (PD) after preoperative biliary stenting. She subsequently presented to the clinic, where it was noticed that she had an elevated CA 19-9. CT C/A/P revealed multiple new liver lesions.

The State of Cancer Care in the United Arab Emirates in 2020: Challenges and Recommendations, A report by the United Arab Emirates Oncology Task Force.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.

A primary retroperitoneal mucinous tumor.

A twenty-five-year-old female presented with a large retroperitoneal mass. Workup included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic exam. After surgical resection, the mass was determined to be a primary retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and few case reports have been published. PRMTs are divided into mucinous cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous carcinoma. These tumors have malignant potential so resection is indicated and in some cases adjuvant chemotherapy and/or surveillance imaging.

Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models.

PURPOSE: Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single-agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor, OSI-906, in combination with a mitogen-activated protein (MAP)-ERK kinase (MEK) 1/2 inhibitor based on evidence that the MAP kinase pathway was upregulated in colorectal cancer cell lines that were resistant to OSI-906. EXPERIMENTAL DESIGN: The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126 were analyzed both as single agents and in combination in 13 colorectal cancer cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. In addition, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) was evaluated in vivo using human colorectal cancer xenograft models. RESULTS: The combination of OSI-906 and U0126 resulted in synergistic effects in 11 of 13 colorectal cancer cell lines tested. This synergy was variably associated with apoptosis or cell-cycle arrest in addition to molecular effects on prosurvival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. CONCLUSIONS: Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with an MEK 1/2 inhibitor in colorectal cancer cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with an MEK inhibitor in patients with colorectal cancer. Clin Cancer Res; 19(22); 6219-29. ©2013 AACR.

Alpha-1-antitrypsin therapy ameliorates acute colitis and chronic murine ileitis.

BACKGROUND: Fecal alpha-1-antitrypsin (AAT) clearance has been a marker of clinical disease severity in inflammatory bowel diseases (IBDs) for many years. Although AAT deficiency is more often associated with lung and liver pathologies, AAT-deficient patients with concomitant IBD have been shown to develop more aggressive disease and rapid progression to surgery. Although recent studies have highlighted the pleiotropic anti-inflammatory functions of AAT, including reducing proinflammatory cytokine production and suppressing immune cell activation, its potential therapeutic role in IBD has not been described. METHODS: The therapeutic potential of human AAT administration was assessed in murine models of IBD including new-onset and established chemically induced colitis and spontaneous chronic murine ileitis. Histological assessment of inflammation, cytokine secretion profiling, and flow cytometric evaluation of inflammatory infiltrate were performed in each model. The effect of AAT on intestinal barrier function was also examined both in vitro and in vivo. RESULTS: AAT attenuated inflammation in small and large intestinal IBD models through reduced secretion of proinflammatory cytokines, inflammatory cell infiltration, and reduced tissue injury. AAT also increased intestinal restitution after chemically induced colitis. AAT significantly decreased intestinal permeability in vitro and in vivo as part of a protective mechanism for both acute and chronic models of IBD. CONCLUSIONS: Our findings describe a beneficial role for AAT in IBD models through suppression of cytokine production and enhanced intestinal barrier function. This raises the possibility that AAT supplementation, which has a long history of proven safety, may have a therapeutic effect in human IBD.

Rational combination of a MEK inhibitor, selumetinib, and the Wnt/calcium pathway modulator, cyclosporin A, in preclinical models of colorectal cancer.

PURPOSE: The mitogen-activated protein kinase (MAPK) pathway is a crucial regulator of cell proliferation, survival, and resistance to apoptosis. MEK inhibitors are being explored as a treatment option for patients with KRAS-mutant colorectal cancer who are not candidates for EGFR-directed therapies. Initial clinical results of MEK inhibitors have yielded limited single-agent activity in colorectal cancer, indicating that rational combination strategies are needed. EXPERIMENTAL DESIGN: In this study, we conducted unbiased gene set enrichment analysis and synthetic lethality screens with selumetinib, which identified the noncanonical Wnt/Ca++ signaling pathway as a potential mediator of resistance to the MEK1/2 inhibitor selumetinib. To test this, we used shRNA constructs against relevant WNT receptors and ligands resulting in increased responsiveness to selumetinib in colorectal cancer cell lines. Further, we evaluated the rational combination of selumetinib and WNT pathway modulators and showed synergistic antiproliferative effects in in vitro and in vivo models of colorectal cancer. RESULTS: Importantly, this combination not only showed tumor growth inhibition but also tumor regression in the more clinically relevant patient-derived tumor explant (PDTX) models of colorectal cancer. In mechanistic studies, we observed a trend toward increased markers of apoptosis in response to the combination of MEK and WntCa(++) inhibitors, which may explain the observed synergistic antitumor effects. CONCLUSIONS: These results strengthen the hypothesis that targeting both the MEK and Wnt pathways may be a clinically effective rational combination strategy for patients with metastatic colorectal cancer.