ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION FOR PANCREATIC ADENOCARCINOMA.

BACKGROUND AND AIMS: Emerging data suggest neoadjuvant chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% demonstrate a meaningful radiographic response to NAC. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC. METHODS: Prospective review of PDAC patients meeting criteria of resectable tumor anatomy that underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging, perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response. RESULTS: Three eligible patients with resectable PDAC received 4 months of NAC plus EUS-RFA. One month after NAC and EUS-RFA completion, all 3 patients underwent standard pancreaticoduodenectomy without complications. After a 6-week recovery, all patients completed 2 months of post-op adjuvant chemotherapy. CONCLUSIONS: In our institutional experience, this treatment protocol appears safe as patients tolerated the combination of chemotherapy and ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.

False-Positive 68 Ga-DOTATATE Uptake in a Uterine Subserosal Fibroid Mimicking Mesenteric Neuroendocrine Tumor : A Case Study.

ABSTRACT: 68 Ga-DOTATATE PET/CT is a highly sensitive and specific imaging modality in detecting neuroendocrine tumors. False-positive DOTATATE uptake poses diagnostic challenges. False-positive uptake in a uterine fibroid is the third most common location. We report the case of a 45-year-old woman with clinical concern for possible neuroendocrine tumor showing moderate focal DOTATATE uptake, which was initially thought of to be localized to mesentery on PET/CT images but was subsequently localized to a subserosal uterine fibroid following MRI. Patient underwent hysterectomy, further confirming that the uterine myometrial uptake is within the subserosal fibroid.

An antibody-drug conjugate targeting GPR56 demonstrates efficacy in preclinical models of colorectal cancer.

BACKGROUND: Long-term prognosis remains poor for colorectal cancer (CRC) patients with advanced disease due to treatment resistance. The identification of novel targets is essential for the development of new therapeutic approaches. GPR56, an adhesion GPCR, is highly expressed in CRC tumours and correlates with poor survival. Here, we describe the generation and preclinical evaluation of a novel ADC consisting of an anti-GPR56 antibody (10C7) conjugated with the DNA-damaging payload duocarmycin. METHODS: RNA-seq dataset analysis was performed to determine GPR56 expression in CRC subtypes. The specificity of binding, epitope mapping, and internalisation of 10C7 was examined. 10C7 was conjugated to payload and ADC cytotoxicity was assessed against a panel of CRC cell lines and tumour organoids. Antitumour efficacy was evaluated in xenograft models of CRC cell lines and patient-derived tumours. RESULTS: High GPR56 was shown to be associated with the microsatellite stable (MSS) subtype that accounts for 80-85% of CRC. GPR56 ADC selectively induced cytotoxicity in CRC cells and tumour organoids at low nanomolar potency in a GPR56-dependent manner and showed significant antitumour efficacy against GPR56-expressing xenograft models. CONCLUSIONS: This study provides the rationale for the future development of a GPR56-targeted ADC approach to potentially treat a large fraction of MSS CRC patients.

How does the tumor microenvironment play a role in hepatobiliary tumors?

The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

Geriatrics: Year in review.

The purpose of this review is to provide an update on topics in general geriatrics that are of interest to the field of geriatric oncology. Based on a review of high-impact journals in geriatrics for the prior two years and reviews of journals in which geriatrics updates are published, updates for hypertension, dementia, vaccination, and frailty are presented here. Recent studies have supported lower, more aggressive blood pressure targets in the management of hypertension, even in older patients. However, controversy remains as to the cognitive and functional effects of aggressive blood pressure targets. Advances in dementia management have been slow, but recent reviews have supported the use of specific screening tools and advocated more widespread screening for mild cognitive impairment and dementia by primary care practitioners. Pharmacologic trials have largely been negative, but a recent multi-component lifestyle intervention showed promise. Significant changes in immunization recommendations have occurred due to two recent large randomized studies of pneumococcal vaccine and a new subunit zoster vaccine. Finally, interventions for frailty syndrome in the geriatric population have been somewhat variable, with some promise in addressing exercise, nutrition, as well as pharmacologic treatment of frailty.

Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia.

To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sß(o) thalassaemia patients from the University of Illinois at Chicago (UIC) and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) cohort. CKD was classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine dipstick with absent red blood cells on microscopy, was confirmed by enzyme-linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was observed in 36% and 20% of the patients, respectively. Pathway analysis in both cohorts indicated an independent association of lactate dehydrogenase with haemoglobinuria and, in turn, independent associations of haemoglobinuria and age with CKD (P < 0·0001). After a median of 32 months of follow-up in the UIC cohort, haemoglobinuria was associated with progression of CKD [halving of estimated glomerular filtration rate or requirement for dialysis; Hazard ratio (HR) 13·9, 95% confidence interval (CI) 1·7-113·2, P = 0·0012] and increasing albuminuria (HR 3·1, 95% CI: 1·3-7·7; logrank P = 0·0035). In conclusion haemoglobinuria is common in SCA and is associated with CKD, consistent with a role for intravascular haemolysis in the pathogenesis of renal dysfunction in SCA.

Mammalian target of rapamycin as a target in hematological malignancies.

The mammalian target of rapamycin (mTOR) regulates protein synthesis in addition to cell growth and cell proliferation. Elucidation of the roles of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in the regulation of the pathogenesis of hematological neoplasms has led to the development and clinical evaluation of agents targeting this pathway for the treatment of leukemia and lymphomas. Clinical trials conducted to date have shown modest responses to mTOR inhibition in patients with various hematological malignancies. Novel agents that simultaneously target mTOR complex 2 (mTORC2) or AKT in addition to mTOR complex 1 (mTORC1) may offer an opportunity to improve therapeutic efficacy.