Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.

Evaluating Pancreatic and Biliary Neoplasms with Small Biopsy-Based Next Generation Sequencing (NGS): Doing More with Less

Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also “liquid biopsies” such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value.

Relationship Between Clustered Ring Nonmass Enhancement of Breast MRI and Prognostic Molecular Biomarkers in Breast Cancer

BackgroundClustered ring enhancement (CRE) of breast MRI is a lexicon of nonmass enhancement (NME) representing tendency of breast cancer and molecular biomarkers are predictors of response to therapy. The purpose of this study was to retrospectively determine the relationship between CRE NME and prognostic molecular biomarkers in breast cancer.MethodsRetrospective analysis of 58 breast lesions in 56 female patients between July 2013 and December 2018 was performed in our institution. Cases with MRI reporting NME in the text were collected via searching the report database. The patterns of enhancement including CRE on breast MRI were reviewed by a radiologist blinded to pathology report. The pathological results and expression of molecular biomarkers were collected. Univariate analysis was applied to evaluate the association between MRI NME imaging features, pathological and IHC stain findings.Results58 Breast lesions were pathologically proven breast carcinoma, and 31 lesions with CRE and 27 lesions without CRE on breast MRI. The expression of estrogen receptor (ER) (P=0.017) and progesterone receptor (PR) (P=0.017) was significantly lower in lesions with CRE compared with those without CRE. The expression of Ki-67 (≥ 25%) was significantly higher in lesions with CRE(P=0.046). The lesions with CRE have a lower expression ratio of ER (50.71 ± 45.39% vs. 74.26 ± 33.59%, p= 0.028).ConclusionOur results indicated that lesions with CRE may possess different features from those without CRE in molecular expression. They tend to bear a more aggressive biological behavior.

Predicting patient treatment response and resistance via single-cell transcriptomics of their tumors

Tailoring the best treatments to cancer patients is an important open challenge. Here, we build a precision oncology data science and software framework for PERsonalized single-Cell Expression-based Planning for Treatments In Oncology (PERCEPTION). Our approach capitalizes on recently published matched bulk and single-cell transcriptome profiles of large-scale cell-line drug screens to build treatment response models from patient single-cell (SC) tumor transcriptomics. First, we show that PERCEPTION successfully predicts the response to monotherapy and combination treatments in screens performed in cancer and patient-tumor-derived primary cells based on SC-expression profiles. Second, it successfully stratifies responders to combination therapy based on the patient tumor SC-expression in two very recent multiple myeloma and breast cancer clinical trials. Thirdly, it captures the development of clinical resistance to five standard tyrosine kinase inhibitors using tumor SC-expression profiles obtained during treatment in a lung cancer patient cohort. Notably, PERCEPTION outperforms state-of-the-art bulk expression-based predictors in all three clinical cohorts. In sum, this study provides a first-of-its-kind conceptual and computational method that is predictive of response to therapy in patients, based on the clonal SC gene expression of their tumors.

Triple negative apocrine breast carcinoma has better prognosis despite poor response to neoadjuvant chemotherapy

Background: Apocrine carcinoma is a rare subtype of invasive ductal breast cancer that shows apocrine differentiation and largely with triple negative immunohistology. Triple negative breast cancers are known to have a more aggressive clinical course. However, unlike the most other types, it is reported that triple negative apocrine carcinoma has a better prognosis. Due to scarcity of reported studies, our knowledges for its clinical behavior, prognosis and response to therapy are very limited. Methods: In this study, we retrospectively retrieved 41 triple negative apocrine carcinoma cases from our breast cancer database with an average follow up 32.8 months.Results: It was found that triple negative apocrine carcinoma had poorer response to neoadjuvant therapy, but better prognosis compared with other non-apocrine types of triple negative breast cancer. Meanwhile, triple negative apocrine carcinoma has a low proliferative nature as indicated by its low Ki67 index. Analysis of SEER database showed that chemotherapy did not improve breast cancer specific survival in TNAC patients. Conclusions: Our results suggest that triple negative apocrine carcinoma is a special subtype of triple negative breast cancer for which de-escalation of chemotherapy should be considered.

Exploring Response to Immunotherapy in Non-Small Cell Lung Cancer Using Delta-Radiomics

Delta-radiomics is a branch of radiomics in which features are confronted after time or after introducing an external factor (such as treatment with chemotherapy or radiotherapy) to extrapolate prognostic data or to monitor a certain condition. Immune checkpoint inhibitors (ICIs) are currently revolutionizing the treatment of non-small cell lung cancer (NSCLC); however, there are still many issues in defining the response to therapy. Contrast-enhanced CT scans of 33 NSCLC patients treated with ICIs were analyzed; altogether, 43 lung lesions were considered. The radiomic features of the lung lesions were extracted from CT scans at baseline and at first reassessment, and their variation (delta, Δ) was calculated by means of the absolute difference and relative reduction. This variation was related to the final response of each lesion to evaluate the predictive ability of the variation itself. Twenty-seven delta features have been identified that are able to discriminate radiologic response to ICIs with statistically significant accuracy. Furthermore, the variation of nine features significantly correlates with pseudo-progression.

Impact of gene polymorphisms on toxicity and response rate in head and neck squamous cell carcinoma: a literature review

Advanced head and neck squamous cell carcinoma (HNSCC) is treated with radiotherapy, chemotherapy, targeted therapy or a combination of these treatments. Variations in toxicity and response to therapy are observed among patients despite similar clinicopathologic characteristics which are attributed to single nucleotide polymorphisms (SNPs). The aim of this review was to evaluate the impact of SNPs on toxicity and response to therapy in HNSCCs. A web-based search of all original articles about the impact of gene polymorphisms on toxicity and response to therapy in HNSCCs was done until September 2021 using international English language databases including Google Scholar, Scopus, PubMed and Web of science. Findings were categorized by type of treatment (radiotherapy, chemotherapy, targeted therapy, or combination therapy). In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. Among studied SNPs with probable impact on toxicity and response to therapy are XRCC1, XRCC3, RAD51, Ku70, NBN, CAT, GSTP1, GSTT1, GSTM1, XPD, XPC, ERCC1, MMP3, ACSL6, EXO1, CXP2D6, FcγRIIIa, AurkA, and EGFR. Understanding gene polymorphisms will help us move toward personalized medicine and determine which patients will actually benefit from therapies for HNSCCs. By examining the SNPs, it is possible to make predictions about the patient's response to treatment or development of toxicity after treatment, and if necessary, make changes in the patient's treatment regimen.

Effects of Prebiotic Supplement on Gut Microbiota, Drug Bioavailability and Adverse Effects in Patients with Colorectal Cancer at Different Primary Tumor Locations Receiving Chemotherapy: Study Protocol for a Randomized Clinical Trial

Background: The prevalence of colorectal cancer (CRC) worldwide is a huge challenge to human health. Primary tumor locations found to impact prognosisand response to therapy. The important role of gut microbiota in the progression and treatment of CRC has led to many attempts of alleviating chemotherapy-induced adverse effects using microecologics. However, the underlying mechanism of the difference in the prognosis of different primary tumor locations and the synergistic effect of prebiotics on chemotherapy need to be further elucidated. This study aims to explore the differences in tumor microbiota and examine the effectiveness of xylooligosaccharides (XOS) on gut microbiota, adverse effects, and bioavailability of chemotherapy drugs in CRC patients at different primary tumor locations.Methods: This is a double-blinded, randomized, parallel controlled clinical trial. Participants with left-sided CRC (LSCRC, n = 50) and right-sided CC (RSCC, n = 50) will randomly allocated to prebiotic group (n = 25) or control group (n = 25) and will receive either a daily XOS (3 g/d) or placebo, respectively, for 12 weeks. The primary outcomes will be the differences in the mucosa microbiota composition at different tumor locations, and differences in gut microbiota composition, adverse effects, and blood concentration of capecitabine posttreatment. The secondary outcomes will include other blood indicators, short-chain fatty acids (SCFAs) concentration, quality of life, and mental health.Discussion: This study will reveal the potential benefits of prebiotic for improving the gut microbiota composition, alleviating the adverse effects, and improving the efficacy of chemotherapy in patients with CRC. In addition, this study will provide data on the different distribution of tumor microbiota and the different changes of gut microbiota during treatment in LSCRC and RSCC, which may provide novel insights into personalized cancer treatment strategies based on primary tumor locations and gut microbiota in the future.Trial registration: Chinese Clinical Trial Registry(www.chictr.org.cn): ChiCTR2100046237. Registered on 12 May 2021.

Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers

PURPOSE In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, RAS-like and BRAF-like, better reflects clinical behavior than sole reliance on pathologic classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer (DTC) and investigate whether mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC. METHODS Somatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into RAS-mutant ( H-K-NRAS), BRAF-mutant ( BRAF p.V600E), and RET/ NTRK fusion ( RET, NTRK1, and NTRK3 fusions) to determine differences between subtype classification in regard to pathologic data (American Joint Committee on Cancer TNM) as well as response to therapy 1 year after initial treatment had been completed. RESULTS Mutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1 year. Patients with RET/ NTRK fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year than patients within RAS- or BRAF-mut subgroups. CONCLUSION Our data support that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathologic classification with patients with RET/ NTRK fusions having worse outcomes than those with BRAF-mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.