Machine learning in metastatic cancer research: Potentials, possibilities, and prospects.

Cancer has received extensive recognition for its high mortality rate, with metastatic cancer being the top cause of cancer-related deaths. Metastatic cancer involves the spread of the primary tumor to other body organs. As much as the early detection of cancer is essential, the timely detection of metastasis, the identification of biomarkers, and treatment choice are valuable for improving the quality of life for metastatic cancer patients. This study reviews the existing studies on classical machine learning (ML) and deep learning (DL) in metastatic cancer research. Since the majority of metastatic cancer research data are collected in the formats of PET/CT and MRI image data, deep learning techniques are heavily involved. However, its black-box nature and expensive computational cost are notable concerns. Furthermore, existing models could be overestimated for their generality due to the non-diverse population in clinical trial datasets. Therefore, research gaps are itemized; follow-up studies should be carried out on metastatic cancer using machine learning and deep learning tools with data in a symmetric manner.

Cecal duplication cyst mimicking intussusception in a female: A case report.

INTRODUCTION: Cecal duplication cysts occur only in 0.4% of all the gastrointestinal tract duplication cysts. More than 80% cases present in the first two years of life. However, asymptomatic individuals may also present in adult life. PRESENTATION OF CASE: A female patient of 42 years presented with generalized abdominal pain and multiple episodes of vomiting from one day. A vague tender mass was palpable in the left lumber region, firm in consistency with ill-defined borders and not moving with respiration. Ultrasound shows mild free fluid with internal debrinous echoic area noted in lower abdomen and pelvis along with fatty hepatomegaly. CeCT scan of the abdomen and pelvis shows twisted appearance of the gut and mesentery in right sub-hepatic region. Complete resection and Ileocolic anastomosis was done along with right hemicolectomy. Based on radiological, surgical and pathological findings, the final diagnosis was enteric duplication cyst. DISCUSSION: Based on their location, terminal ileum and ileocecal junction are the most common sites (53 %) with colonic duplication second to it (13%). However, cecal duplication cysts remain the least common with incidence of 0.4 % only. Females are more common than males. However, their exact cause is not known. Possible causes are defective recanalization, fusion of embryonal longitudinal folds, persistant diverticulae of embryonic life and uterine vascular anomalies. CONCLUSION: Enteric duplication cysts most commonly presenting with palpable abdominal mass, pain mimicking appendicitis & bleeding per-rectum. The treatment of choice is resection and ileocolic anastomosis with overall good prognosis. The delay in the diagnosis can lead to high mortality.

Secondary Tumors of the Kidney: A Comprehensive Clinicopathologic Analysis.

Metastases to the kidney are rare and were historically described in autopsy series, and the incidence ranged between 2.36% and 12.6%. However, in the contemporary literature with the improvements in imaging modalities (computed tomography scan and magnetic resonance imaging) and other health care screening services, metastatic tumors to the kidney are being diagnosed more frequently in surgical specimens. The utility of needle core biopsies in the primary evaluation of renal masses has also increased the number of sampled metastases, and as a result, only limited histologic material is available for evaluation in some cases and may potentially lead to diagnostic pitfalls. In the last decade, a few large clinical series have been published. In these series, the majority of metastatic tumors to the kidney are carcinomas, with the lung being the most common primary site. A significant number of the various tumor types with metastasis to the kidney are also associated with widespread metastases to other organs, and the renal metastasis may present several years after diagnosis of the primary tumor. The majority of secondary tumors of the kidney are asymptomatic, incidentally discovered, and solitary. There should be a high index of suspicion of metastasis to the kidney in patients with an associated enlarging renal lesion with minimal to no enhancement on imaging and tumor progression of a known high-grade nonrenal malignancy. Secondary tumors of the kidney can be accurately diagnosed by correlating histopathologic features with clinical and radiographic findings and the judicious use of ancillary studies.

[18F]Fluciclovine Positron Emission Tomography/Computerized Tomography for Preoperative Staging in Patients with Intermediate to High Risk Primary Prostate Cancer.

PURPOSE: Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [18F]fluciclovine positron emission tomography/computerized tomography is an early indicator of subclinical metastasis among patients with high risk prostate cancer. MATERIALS AND METHODS: A total of 68 patients with unfavorable intermediate to very high risk prostate cancer without systemic disease on conventional imaging were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection. Diagnostic performance of [18F]fluciclovine positron emission tomography/computerized tomography and conventional imaging for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined. RESULTS: Overall 57 of 68 patients completed the protocol, of whom 31 had nodal metastasis on histology. [18F]Fluciclovine positron emission tomography/computerized tomography sensitivity and specificity in detecting nodal metastasis was 55.3% and 84.8% per patient, and 54.8% and 96.4% per region (right and left pelvis, presacral and nonregional), respectively. Compared with conventional imaging [18F]Fluciclovine positron emission tomography/computerized tomography had significantly higher sensitivity on patient based (55.3% vs 33.3%, p <0.01) and region based (54.8% vs 19.4%, p <0.01) analysis, detecting metastasis in 7 more patients and 22 more regions, with similar high specificity. Four additional patients had distant disease or other cancer detected on [18F] fluciclovine positron emission tomography/computerized tomography which precluded surgery. Detection of metastasis was related to size of metastatic deposits within lymph nodes and overall metastatic burden. CONCLUSIONS: [18F]Fluciclovine positron emission tomography/computerized tomography detects occult metastases not identified on conventional imaging and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.

Primary effusion lymphoma of the pleural space: Report of a rare complication of cardiac transplant with review of the literature.

Primary effusion lymphoma (PEL) is a rare mature B-cell non-Hodgkin's lymphoma arising in body cavities and presenting with effusions. It has been described predominantly in patients with impaired immunity from the acquired immunodeficiency syndrome and is associated with the Human Herpesvirus-8 (HHV-8). Seldom has PEL been diagnosed in persons negative for the human immunodeficiency virus (HIV), and in such cases it has occurred primarily in the setting of posttransplant immunosuppression. We report an instructive case of a Caribbean-American HIV-negative orthotopic heart transplant recipient with a history of HHV-8-associated Kaposi's sarcoma who developed HHV-8 viremia and PEL of the pleural space early in the posttransplant course. This case highlights the importance of considering PEL in the differential diagnosis of a new pleural effusion in a transplant recipient at risk for HHV-8-associated disease.

Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease.

Alzheimer's disease, one of the most important brain pathologies associated with neurodegenerative processes, is related to overactivation of calpain-mediated proteolysis. Previous data showed a compelling efficacy of calpain inhibition against abnormal synaptic plasticity and memory produced by the excess of amyloid-ß, a distinctive marker of the disease. Moreover, a beneficial effect of calpain inhibitors in Alzheimer's disease is predictable by the occurrence of calpain hyperactivation leading to impairment of memory-related pathways following abnormal calcium influxes that might ensue independently of amyloid-ß elevation. However, molecules currently available as effective calpain inhibitors lack adequate selectivity. This work is aimed at characterizing the efficacy of a novel class of epoxide-based inhibitors, synthesized to display improved selectivity and potency towards calpain 1 compared to the prototype epoxide-based generic calpain inhibitor E64. Both functional and preliminary toxicological investigations proved the efficacy, potency, and safety of the novel and selective calpain inhibitors NYC438 and NYC488 as possible therapeutics against the disease.

Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models.

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, pursuit of the neurotherapeutic hypothesis requires kinase isoform selective inhibitors with appropriate neuropharmacology features. Synaptic dysfunction disorders offer a potential for enhanced pharmacological efficacy due to stress-induced activation of p38αMAPK in both neurons and glia, the interacting cellular components of the synaptic pathophysiological axis, to be modulated. We report a novel isoform selective p38αMAPK inhibitor, MW01-18-150SRM (=MW150), that is efficacious in suppression of hippocampal-dependent associative and spatial memory deficits in two distinct synaptic dysfunction mouse models. A synthetic scheme for biocompatible product and positive outcomes from pharmacological screens are presented. The high-resolution crystallographic structure of the p38αMAPK/MW150 complex documents active site binding, reveals a potential low energy conformation of the bound inhibitor, and suggests a structural explanation for MW150's exquisite target selectivity. As far as we are aware, MW150 is without precedent as an isoform selective p38MAPK inhibitor or as a kinase inhibitor capable of modulating in vivo stress related behavior.