Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients

AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P< 0.001) and preoperative serum levels of CEA (P=0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented signif icant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RTPCR assay can provide useful information concerning disease stage and overall survival of CRC patients.

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcino-mas. Here a rare case of lymphoepithelioma-like hepa-tocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonogra-phy revealed a liver nodule, 2.2 cm in diameter, local-ized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nod-ule was hypoechogenic. The patient underwent sur-gery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a promi-nent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic sup-pressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-edge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carci-noma. The association between the lack of EBV infec-tion, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.

Sentinel lymph node biopsy in clinically detected ductal carcinoma in situ

AIM:To study the indications for sentinel lymph node biopsy(SLNB) in clinically-detected ductal carcinoma in situ(CD-DCIS).METHODS:A retrospective analysis of 20 patients with an initial diagnosis of pure DCIS by an image-guided core needle biopsy(CNB) between June 2006 and June 2012 was conducted at King Faisal Specialist Hospital.The accuracy of performing SLNB in CD-DCIS,the rate of sentinel and non-sentinel nodal metastasis,and the histologic underestimation rate of invasive cancer at initial diagnosis were analyzed.The inclusion criteria were a preoperative diagnosis of pure DCIS with no evidence of invasion.We excluded any patient with evidence of microinvasion or invasion.There were two cases of mammographically detected DCIS and 18 cases of CDDCIS.All our patients were diagnosed by an imageguided CNB except two patients who were diagnosed by fine needle aspiration(FNA).All patients underwent breast surgery,SLNB,and axillary lymph node dissection(ALND) if the SLN was positive.RESULTS:Twenty patients with an initial diagnosis of pure DCIS underwent SLNB,2 of whom had an ALND.The mean age of the patients was 49.7 years(range,35-70).Twelve patients(60%) were premenopausal and 8(40%) were postmenopausal.CNB was the diagnostic procedure for 18 patients,and 2 who were diagnosed by FNA were excluded from the calculation of the underestimation rate.Two out of 20 had a positive SLNB and underwent an ALND and neither had additional non sentinel lymph node metastasis.Both the sentinel visualization rate and the intraoperative sentinel identification rate were 100%.The false negative rate was 0%.Only 2 patients had a positive SLNB(10%) and neither had additional metastasis following an ALND.After definitive surgery,3 patients were upstaged to invasive ductal carcinoma(3/18 = 16.6%) and 3 other patients were upstaged to DCIS with microinvasion(3/18 = 16.6%).Therefore the histologic underestimation rate of invasive disease was 33%.CONCLUSION:SLNB in CD-DCIS is technically feasible and highly accurate.We recommend limiting SLNB to patients undergoing a mastectomy.

Identify multiple myeloma stem cells: Utopia?

Multiple myeloma(MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells(CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activate stemness signaling(Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

Hepatic steatosis in overweight/obese females: New screening method for those at risk

AIM: To identify which parameters could help to distinguish the "metabolically benign obesity", which is not accompanied by insulin resistance (IR) and early atherosclerosis.METHODS: Eighty two of 124 overweight/obese females formed the study population, which was divided into two groups (52 and 30 subjects, respectively) with and without IR according to a HO meostatic Metabolic Assessment (HOMA) cut-off of 2, and were studied in a cross-sectional manner. The main outcome measures were waist circumference, serum uric acid, high-density lipoprotein-cholesterol and triglycerides, alanine amino-transferase, blood pressure and the two imaging para-meters, hepatic steatosis and longitudinal diameter of the spleen, which were measured in relation to the presence/absence of IR. RESULTS: A variable grade of visceral obesity was observed in all subjects with the exception of three.Obesity of a severe grade was represented more in the group of IR individuals (P = 0.01). Hepatic steatosis, revealed at ultrasound, was more pronounced in IR than in non-IR subjects (P = 0.005). The two groups also demonstrated a clear difference in longitudinal spleen diameter and blood pressure, with raised and signif icant values in the IR group. Metabolic syndrome was frequent in the IR group, and was not modified when adjusted for menopause (P = 0.001). At linear regression, the β values of waist circumference and body mass index predicting HOMA were 0.295, P = 0.007 and 0.41, P = 0.0001, respectively. Measures of spleen longitudinal diameter were well predicted by body mass index (BMI) values, β = 0.35, P = 0.01, and by HOMA, β = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, β = 0.39, P = 0.0001). HOMA and hepatic steatosis were highly associated (rho = 0.34, P = 0.002). Interestingly, IR patients were almost twice as likely to have hepatic steatosis as non-IR patients. Among the MS criteria, blood pressure was very accurate in identifying the presence of IR (AUROC for systolic blood pressure 0.66, cut-off 125 mm of Hg, sensibility 64%, specif icity 75%; AUROC for diastolic blood pressure 0.70, cut-off 85 mm of Hg, sensibility 54.5%, specif icity 75%). CONCLUSION: As health care costs are skyrocketing, reliable and mainly inexpensive tools are advisable to better defi ne subjects who really need to lose weight.

Activity and safety of pegylated liposomal doxorubicin,5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma:A phase Ⅱ study

AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.

How would preclinical Alzheimer’s disease (AD pathology) occur? An insight from a genomic instability mouse model

More than 95%of Alzheimer’s disease(AD)is late-onset,in which patients show clinical cognition/behavior symptoms after age 65.Unlike early-onset AD that comes with mutations in genes directly involved in amyloid metabolism(APP,PSEN),genetic predispositions associated with late-onset AD are harder to pinpoint,and their mechanistic links to AD development need further investigation.Although the development mechanism of late-onset AD remains controversial,amyloid-beta accumulation,initiated in middle age,is widely accepted as the triggering event for early AD pathology(Du Bois et al.,2010;Sterling et al.,2011).

Magnetic resonance imaging:Is there a role in clinical management for acute ischemic colitis?

AIM:To validate the utility of magnetic resonance imaging(MRI) for the clinical management of acute ischemic colitis(IC).METHODS:This is a magnetic resonance(MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical,endoscopic and computed tomography(CT) findings and who were imaged in our institution between February 2011 and July 2012.The mean age of the patients was 72.28 years.Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans,in the late arterial phase(start delay 45-50 s) and in the portal venous phase(start delay 70-80 s).The MR examinations were performed using a 1.5T superconducting magnet,using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane.CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings.RESULTS:Segmental involvement was seen in 6 patients(85.71%),with a mean length of involvement of 412 mm(range 145.5-1000 mm).Wall thickness varied between 6 mm and 17.5 mm(mean 10.52 mm) upon CT examinations and from 5 to 15 mm(mean 8.8 mm) upon MR examinations.The MRI appearance of the colonic wall varied over the time:TypeⅠappearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations(41.66%),patients underwent MR within a mean of 36 h(ranging from 1 to 54 h) after the CT examination.Type Ⅱ and Ⅲ appearance with a 2 layer sign,was seen in 4 examinations(33.33%),patients underwent MR within a mean of 420.5 h(ranging from 121 to 720 h) after the CT examination.In the remaining three MRI examinations,performed within a mean of 410 h(ranging from 99.5 to 720 h) the colonic wall appeared normal.CONCLUSION:MRI,only using precontrast images,may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC.

Notes for developing a molecular test for the full characterization of circulating tumor cells

The proved association between the circulating tumor cell （CTC） levels and the patients＇ survival parameters has been growing interest to investigate the molecular profile of these neoplastic cells among which hide out precursors capable of initiating a new distant metastatic lesion. The full characterization of the tumor cells in peripheral blood of cancer patients is expected to be of help for understanding and （prospectively） for counteracting the metastatic process. The major hitch that is hampering the successful gaining of this result is the lack of a consensus onto standard operating procedures （SOPs） for performing what we generally define as the ＂liquid biopsy＂. Here we review the more recent acquisitions in the analysis of CTCs and tumor related nucleic acids, looking to the main open questions that are hampering their definitive employ in the routine clinical practice.

Lung adenocarcinoma harboring rare epidermal growth factor receptor L858R and V834L mutations treated with icotinib:A case report

BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors,which bring uncertainty to clinical treatment.CASE SUMMARY A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain.Chest computed tomography revealed lung spaceoccupying lesions and multiple lymphadenectasis.Bronchoscopy and pathology suggested lung adenocarcinoma.Compound variation of EGFR gene(exon 21 L858 R/V834 L)was detected in both tissue and circulating tumor deoxyribonucleic acid samples.As a result of next-generation sequencing and her family’s wishes,the patient was given oral treatment with icotinib hydrochloride(125 mg/d,tid)from March 21,2019 and has achieved stable disease for the last 1 year.CONCLUSION Non-small cell lung adenocarcinoma with EGFR L858 R/V834 L was treated successfully with icotinib,and it may be a new medication treatment option.

Helical tomotherapy for duodenal adenocarcinoma in an elderly patient: A case report

To evaluate the efficacy and feasibility of external beam radiotherapy(EBRT) for duodenal adenocarcinoma in an 84-year-old female who underwent EBRT(2.2 Gy/d for a total dose of 46.2 Gy) using helical tomotherapy(HT). Toxicity was evaluated on the National Cancer Institute's common toxicity criteria(CTCAE 3.0). The patient completed the treatment without G3-G4 toxicity. After 22-mo follow-up, she is alive and well, in complete remission with no late side effects. HT seems to be feasible and effective for duodenal adenocarcinoma in old to very old patients.

Association between Pretreatment Levels of Serum Vascular Endothelial Growth Factor (VEGF) and Survival Outcomes in Locally Advanced Cervical Cancer Patients

Objective: To evaluate the association between pretreatment levels of serum vascular endothelial growth factor (VEGF) and long-term treatment outcomes in patients with locally advanced cervical cancer (LACC). Methods: Thirty-nine patients diagnosed with LACC (stage IIB-IVA) and obtaining blood for serum VEGF were identified. All patients received complete treatment as radical radiotherapy with or without concurrent chemotherapy. Surveillance for all patients was every 3 months during the first 2 years, and every 6 months later. Results: Mean age of 39 patients was 52.3 ± 10.8 years old. Twenty-three patients (59.0%) had stage IIB, and 16 patients (41.0%) had stage IIIB. Histological cell type was mostly squamous cell carcinoma (89.7%). The median and 75th percentile level of serum VEGF were 610.2 pg/ml (0.0 - 4067.2 pg/ml) and 825.6 pg/ml, respectively. At median follow-up of 37.0 months (range, 26.8 - 46.3 months), the 3-year OS rate was 78.6%. Clinical stage (p = 0.04) and 75th percentile of VEGF level (p = 0.04) were impacted on OS in univariable analysis. The 3-year OS of patients in stage IIB with serum VEGF of ≤825.6 pg/ml and of > 825.6 pg/ml was slightly different, 94.4% and 80.0% respectively (p = 0.34), whereas there were many differences in stage IIIB, 71.4% and 25.0% in patients with serum VEGF of ≤825.6 pg/ml and of >825.6 pg/ml respectively (p = 0.05). Conclusion: High pretreatment serum VEGF level has an influence on OS for LACC. It is potentially used as a predictive factor, especially in patients stage IIIB, in order to provide efficient treatment and improve survival outcomes in the future.

IGF2BP3-induced activation of EIF5B contributes to progression of hepatocellular carcinoma cells

In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.

丹麦北日德兰半岛卵巢上皮癌集中进行初次手术的疗效

Objective. The study was performed to evaluate the results of treatment of ovarian carcinoma after the introduction of centralised primary surgery in the County of North Jutland, Denmark. Method. Prospective study of consecutive cases of ovarian cancer undergoing primary surgical treatment at the Gynecologic Oncologic Center after the introduction of centralised primary surgery. Results of treatment recorded up to the date of last examination or death. Results. From 1999 to 2002, 107 patients with primary epithelial ovarian cancer underwent primary surgery at the Gynecologic Oncologic Center, Aalborg. This corresponds to 95.5%of patients with invasive carcinoma in the County of North Jutland. All patients with Stage I to Stage IIIB disease had a complete, macroscopically radical cytoreduction performed. In patients with Stage III and IV invasive tumors, the optimal debulking rate was 79.5%, and, in Stage IIIC and IV, the optimal debulking rate was 78.2%. Intra-operative and post-operative complications were generally few. Post-operative death, defined as death within 30 days after surgery, was observed in 4 cases (3.7%). After primary surgery, platinum-based chemotherapy was given in most cases. For Stage I to IV invasive cancer, the median survival was 46 months. In patients with Stage IIIC and IV disease, the median survival was 32 months. In optimally debulked Stage IIIC and IV disease, the median survival was 41 months. Conclusions. The results in dicate a survival benefit after introduction of centralised primary surgery. Compared to existing national and regional data on survival in ovarian cancer, the results indicate an increase in median survival for all stages of approximately 15 months. Centralisation of primary surgery to centres with the necessary expertisemay be the most significant way to increase survival in ovarian cancer in Denmark.

晚期卵巢透明细胞癌:希腊肿瘤协作组的研究

Purpose.:Ovarian clear-cell carcinomas (OCCC) are known to be possibly resistant to platinum-based chemo- therapy and to have a poorer prognosis with respect to other subtypes of epithelial ovarian cancer (EOC). This study was undertaken to compare response and survival to platinum-based chemotherapy between patients with advanced stage III and IV OCCC and serous EOC (sEOC). Patients and methods.:A retrospective analysis was performed in patients with advanced stage of OCCC treated with first-line platinum-based chemotherapy in the context of several study protocols of the Hellenic Cooperative Oncology Group (HeCOG) between 1/2/1987 and 31/10/2003. The outcome was compared to that of patients with sEOC treated according to the same protocols during the same study period. Results.:One hundred and five patients (35 stage III and IV OCCC,70 stage III and IV sEOC) treated with platinum-based chemotherapy were analyzed. The overall response rate for OCCC was 45%(complete response 25%) (95%CI,23.1%to 68.5%) and 81%(complete response 46%) (95%CI,67.4%to 91.1%) for sEOC. The overall response rate was significantly higher for sEOC (P = 0.008). In the subgroup of stage III patients,the rate of complete responders was higher among sEOC patients (P = 0.023). After a median follow-up of 61.1 months,median survival and time to tumor progression were not significantly different between the two groups (25.1 months 95%CI 11.7 to 38.5 months versus 49.1months 95%CI 36.5 to 61.6 months ,P = 0.141,12.0 months 95%CI 6.5 to 17.3 months versus 18.0 months 95%CI 14.7 to 21.6 months ,P = 0.384,respectively). Conclusion.:Patients with OCCC have significantly lower response to platinum-based first-line chemotherapy compared to patients with sEOC. This low response to platinum-based chemotherapy was not translated in significantly shorter survival. The current study outcomes are provocative and suggest that a new strategy for chemotherapy in OCCC should be adopted,possibly one that focuses on new agents without cross-resis- tance to platinum agents.

First-line pazopanib in patients with advanced non-clear cell renal carcinoma:An Italian case series

BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.

Proximal humerus reconstruction in orthopedic oncology

Proximal humeral reconstructive options following radical resection of proximal humeral primary and metastatic bone malignancies have evolved over time.With the relatively recent advent of the reverse total shoulder(RTSA),this technique has been increasingly employed in this setting over hemiarthroplasty techniques.An array of options,including proximal humeral allograft-prosthetic composites(including both RTSA and hemiarthroplasty),megaprostheses,and osteoarticular allografts,is reviewed from the perspective of their indications,techniques,complications,and published results.An extensive case-based pictorial presentation illustrates these options.