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Seminars in Diagnostic Pathology May 2018The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently,... (Review)
Review
The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).
Topics: Biomarkers, Tumor; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Heredity; High-Throughput Screening Assays; Humans; Immunohistochemistry; Mutation; Neoplastic Syndromes, Hereditary; Pathology, Molecular; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 28662997
DOI: 10.1053/j.semdp.2017.05.004 -
European Radiology Nov 2017To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver...
PURPOSE
To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver metastasis undergoing transarterial (chemo)embolization (TACE/TAE).
MATERIAL AND METHODS
This was a HIPAA-compliant institutional review board-approved single-institution retrospective review of 95 non-cirrhotic patients (52 men; mean age, 60 years) who underwent CBCTA prior to (chemo)embolic delivery. IHM were defined by the presence of innumerable subcentimetre hepatic parenchymal hypevascular foci not detected on pre-TACE/TAE contrast-enhanced cross-sectional imaging. Multivariate analysis was performed to compare time to tumour progression (TTP) between patients with and without IHM.
RESULTS
IHM were present in 21 (22%) patients. Patients with IHM had a significantly shorter intrahepatic TTP determined by a higher frequency of developing new liver metastasis (hazard ratio [HR]: 1.99; 95% confidence interval [CI] 1.08-3.67, P= 0.02). Patients with IHM trended towards a shorter TTP of the tumour(s) treated with TACE/TAE (HR: 1.72; 95% CI: 0.98-3.01, P= 0.056). Extrahepatic TTP was not significantly different between the two cohorts (P= 0.27).
CONCLUSION
Patients with IHM on CBCTA have worse prognosis due to a significantly higher risk of developing new hepatic tumours. Further work is needed to elucidate its underlying mechanisms of pathogenesis.
KEY POINTS
• 21% of liver metastasis patients undergoing TACE/TAE have IHM on CBTA. • IHM are associated with a high risk of developing new hepatic tumours. • IHA are also associated with a trend toward poorer response to TACE/TAE.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Computed Tomography Angiography; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Proportional Hazards Models; Retrospective Studies
PubMed: 28484824
DOI: 10.1007/s00330-017-4847-3 -
The Lancet. Oncology Apr 2017Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for...
BACKGROUND
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
METHODS
We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
RESULTS
We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
INTERPRETATION
To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
FUNDING
National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Anus Neoplasms; Carcinoma, Squamous Cell; Case-Control Studies; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nivolumab; Prognosis; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Salvage Therapy; Survival Rate
PubMed: 28223062
DOI: 10.1016/S1470-2045(17)30104-3 -
Journal of Hepatocellular Carcinoma 2016Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic... (Review)
Review
Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques.
PubMed: 27785450
DOI: 10.2147/JHC.S92732 -
Journal of Hepatocellular Carcinoma 2016The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well...
PURPOSE
The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well established. We determined the incidence of adverse events with this combination therapy in patients with advanced HCC at our institution and analyzed the treatment and survival outcomes.
MATERIALS AND METHODS
We reviewed the records of 19 patients with Barcelona Clinic Liver Cancer class B or C HCC who underwent treatment with Y90 RMS (for 21 sessions) while receiving full or reduced doses of sorafenib between January 2008 and May 2010. Therapy response was evaluated using Response Evaluation Criteria in Solid Tumors. We evaluated median overall survival (OS) and progression-free survival (PFS) as well as hepatic and extrahepatic disease PFS and incidence of adverse events.
RESULTS
The median patient age was 67 years, and portal or hepatic venous invasion was present in eight patients (42%). Ten patients received reduced doses of sorafenib. The median Y90 radiation activity delivered was 41.2 mCi. The partial response of Response Evaluation Criteria in Solid Tumors was observed in four patients (19%). The median hepatic disease PFS was 7.82 months, extrahepatic disease PFS was 8.94 months, OS was 19.52 months, and PFS was 6.63 months. Ninety days after treatment with Y90 RMS, five patients (26%) had grade II adverse events and four patients (21%) had grade III adverse events.
CONCLUSION
OS and PFS outcomes were superior to those observed in prior studies evaluating sorafenib alone in patients with a similar disease status, warranting further study of this treatment combination.
PubMed: 27574586
DOI: 10.2147/JHC.S62261 -
Journal of Gastrointestinal Surgery :... Jun 2016The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of...
BACKGROUND
The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response.
OBJECTIVE
The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy.
METHODS
All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed.
RESULTS
Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6-20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n = 31) or ablation (n = 10). After median follow-up of 14 months (range, 0-64 months), no local recurrences were observed.
CONCLUSION
Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Colorectal Neoplasms; Fiducial Markers; Follow-Up Studies; Hepatectomy; Humans; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Retrospective Studies; Treatment Outcome
PubMed: 26791387
DOI: 10.1007/s11605-016-3079-1 -
Journal of Oral Biology and... 2014The use of natural plant extracts in pharmacology, medicine and dental hygiene has found a growing interest in modern scientific research. Salvadora persica is a natural...
AIMS
The use of natural plant extracts in pharmacology, medicine and dental hygiene has found a growing interest in modern scientific research. Salvadora persica is a natural tree whose fibrous branches have been approved by the World Health Organization for oral hygiene. Periodontitis is a highly prevalent adult gingival disease that leads to bone destruction and connective tissue attachment loss. The aim of this research was assessment the antimicrobial activities of methanolic extract of Salvadora persica (miswak) on isolated strains from the oral fluid.
METHODS
In practical section, 50 female university students (21.4 ± 1 year) participated in the study. Based on examination by a periodontist, they were grouped into (Group I, n = 21) and (Group II, n = 29) i.e. with and without periodontitis respectively. Their un-stimulated saliva samples were obtained in sterile tubes. While three bacterial genera, Staphylococcus, Streptococcus and Lactobacillus were identified in all subjects, Enterococcus and Escherichia were only detected in Group I.
RESULTS
A statistically significant difference in colonization levels between the two groups was observed. The effect of methanolic extract of S. persica against oral bacterial strains isolated from saliva was investigated using agar disc diffusion and microdilution methods. Although methanolic extract of S. persica was effective on growth inhibition of all strains, it was significantly more effective on Gram positive bacteria than Gram negative ones.
CONCLUSIONS
Effective substances present in S. persica extracts, exhibit a broad range of antibacterial activity and affect almost all bacterial species regardless of the Gram-staining nature.
PubMed: 25737914
DOI: 10.1016/j.jobcr.2014.01.001 -
Journal of the American College of... Jul 2013The primary reported indication for the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) technique is in patients with very low... (Comparative Study)
Comparative Study
Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume, including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach.
BACKGROUND
The primary reported indication for the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) technique is in patients with very low future liver remnant volumes. Given the elevated incidence of major morbidity (40%) and liver-related mortality (12%) with ALPPS, we sought to determine the safety and efficacy of percutaneous portal vein embolization (PVE) in a similar patient population.
STUDY DESIGN
Tumor resectability and morbidity and mortality rates were reviewed for 144 consecutive liver tumor patients with future liver remnant to body weight ratios (LR/BW) less than 0.5%. All patients were referred for preoperative percutaneous right plus segment IV PVE using embolic microspheres, with planned reassessment of the LR/BW 30 days after PVE. Post-PVE outcomes were compared with reported outcomes for ALPPS.
RESULTS
Percutaneous PVE was successfully performed in 141 of the 144 study patients (97.9%). Adequate regeneration was observed in 139 patients (98.5%) with median post-PVE LR/BW rising from 0.33% to 0.52% (p < 0.0001), representing a per-patient median regeneration rate of 62% (range 0.3% to 379%). In total, 104 patients underwent extended right hepatectomy (n = 102) or right hepatectomy (n = 2). The remaining 40 patients (27.8%) were not resectable due to short-interval disease progression (27 patients, 18.5%), insufficient liver regeneration (5 patients, 3.5%), and medical comorbidities (8 patients, 5.6%). After resection, the following outcomes were observed: major morbidity: 33.0% (34 of 104), liver insufficiency: 12.5% (13 of 104), and 90-day liver-related mortality: 5.8% (6 of 104). These oncologic and technical results compare favorably with those of ALPPS.
CONCLUSIONS
Based on its ability to select oncologically resectable patients and superior safety and efficacy profiles, percutaneous right + segment IV PVE and interval surgery remains the standard of care for patients with very low future liver remnant volumes.
Topics: Adult; Aged; Embolization, Therapeutic; Female; Follow-Up Studies; Hepatectomy; Humans; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Male; Microspheres; Middle Aged; Organ Size; Portal Vein; Preoperative Care; Survival Analysis; Treatment Outcome
PubMed: 23632095
DOI: 10.1016/j.jamcollsurg.2013.03.004 -
Chinese Journal of Cancer Jun 2013Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of... (Review)
Review
Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.
Topics: Combined Modality Therapy; Gastrinoma; Glucagonoma; Humans; Insulinoma; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Vipoma; von Hippel-Lindau Disease
PubMed: 23237225
DOI: 10.5732/cjc.012.10295 -
Endocrinologia Y Nutricion : Organo de... Nov 2012We have described a novel Mahvash disease of hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an inactivating glucagon receptor mutation,...
BACKGROUND AND AIM
We have described a novel Mahvash disease of hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an inactivating glucagon receptor mutation, and identified the glucagon receptor-deficient (Gcgr(-/-)) mice as its murine model. We aim to elucidate the natural history of the rare Mahvash disease by long-term observation of the Gcgr(-/-) mice.
MATERIALS AND METHOD
Wild type (WT) (n=52), heterozygous (n=127), and Gcgr(-/-) (n=56) mice living under standard vivarium conditions were observed without specific treatments over 22 months. Autopsy was performed on dead animals.
RESULTS
The WT and heterozygous mice did not exhibit any measurable differences. The Gcgr(-/-) mice became progressively lethargic and cachexic after 12 months. Random glucose levels were stable in WT and heterozygous mice but decreased with age in the Gcgr(-/-) mice. At the end of observation, 28/56 Gcgr(-/-), 7/52 WT, and 24/127 heterozygous mice died. The survival curve of Gcgr(-/-) mice began to separate from those of WT and heterozygous mice at 12 months and the survival difference widened with age. At 18 months, survival probability was 17% for Gcgr(-/-) mice but 77% for WT and 81% for heterozygous mice. Autopsy revealed numerous PNETs up to 15 mm in diameter in most well-preserved Gcgr(-/-) pancreata (17/20) but none in WT or heterozygous ones. Four Gcgr(-/-) mice developed liver or subcutaneous metastasis.
CONCLUSION
The untreated Mahvash disease may cause cachexia, severe hypoglycemia, and early death. Patients with Mahvash disease need to undergo life-long surveillance for PNETs. Functional glucagon receptor is thus required for long-term survival.
Topics: Animals; Blood Glucose; Cachexia; Disease Models, Animal; Disease Progression; Female; Glucagon; Humans; Hypoglycemia; Lethargy; Liver Neoplasms; Longevity; Male; Mice; Mice, Inbred DBA; Mice, Knockout; Neoplastic Syndromes, Hereditary; Neuroectodermal Tumors, Primitive, Peripheral; Pancreatic Neoplasms; Receptors, Glucagon; Skin Neoplasms
PubMed: 22951296
DOI: 10.1016/j.endonu.2012.06.006