Histopathological Response Research Articles

Correlation between histopathological response by neoadjuvant DCF therapy and the clinical efficacy of palliative platinum-containing regimens for recurrent ESCC.

272 Background: Docetaxel and cisplatin, 5-FU (DCF) therapy has established as the standard neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. If patients showed recurrence of ESCC after neoadjuvant DCF therapy, platinum-containing regimens were used as palliative treatment in the clinical practice. However, there were no data of correlation between histopathological response by neoadjuvant DCF therapy and clinical efficacy of palliative platinum-containing regimens for recurrent ESCC. Methods: We retrospectively reviewed patients with ESCC who received neoadjuvant DCF therapy and R0 resection between Feb 2014 to June 2022 in our hospital. We evaluated histopathological response by neoadjuvant DCF therapy based on the Japanese Classification of Esophageal Cancer 12th (Grade 0: ineffective, Grade 1: slightly effective, Grade 2: moderately effective, Grade 3: markedly effective [pT0]) and objective response rate (ORR), progression-free survival (PFS) during platinum-containing regimens as clinical efficacy outcomes. We analyzed the correlation between histopathological response and ORR, PFS using Fisher’s exact tests and the log-rank tests. In addition, we analyzed clinical factors related to clinical efficacy of palliative chemotherapy using Cox proportional hazards models. Results: In this study, 398 patients received neoadjuvant DCF therapy and we identified 88 eligible patients with recurrence. Among 88 patients, 33 patients initially received palliative chemotherapy and analyzed. Patients’ characteristics were followed; Male/Female: 26 (78.8%)/7 (21.2%), median age (range): 64 (46-76) years, PS 0/1/2: 1 2(36.4%)/17 (51.5%), 4 (12.1%). Histopathological response 0/1/2/3 were in 1 (3.0%)/23 (69.7%)/7 (21.2%)/2 (6.1%) patients, respectively. Among these 33 patients, 23 patients received platinum-containing regimens. In the patients who received palliative chemotherapy, the ORR were 34.8% (8/23) in histopathological response 0/1 group and 44.4% (4/9) in histopathological response 2/3 group, with no statistical difference (p = 0.696). The median PFS was 2.43 (95%CI: 2.33-2.53) months in histopathological response 0/1 group and 4.04 (95%CI: 0-10.77) months in histopathological 2/3 group (HR[95%CI]: 1.121 [0.413-3.043]). Multivariate analysis using Cox proportional hazards models revealed chemotherapy-free-interval (CFI) < 6 months (HR[95%CI]: 3.594 [1.027–12.580]) was independent prognostic factor, whereas histopathological response didn’t show the significance (HR[95%CI]: 0.723 [0.195–2.678]). Conclusions: Histopathological response by neoadjuvant DCF therapy did not affect the efficacy of platinum-containing regimens for recurrent ESCC, while CFI might be the prognostic factors.

FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)—Primary safety and short-term efficacy results for cohort E.

326 Background: The standard neoadjuvant treatment in Japan for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is DTX + CDDP + 5-FU (DCF). In addition, immune checkpoint inhibitors (ICIs) have shown a survival benefit for ESCC and are promising as neoadjuvant treatment for several cancers. We previously reported that neoadjuvant CDDP + 5-FU + nivolumab (Nivo) or DCF + Nivo therapy was tolerable and showed promising efficacy for ESCC. However, the efficacy of neoadjuvant treatment and safety of subsequent surgery remain unclear for 5-FU + l-LV + L-OHP + DTX (FLOT), the global standard of care for perioperative esophagogastric adenocarcinoma, plus ICI for ESCC. Methods: JCOG1804E (FRONTiER) is a multi-cohort phase I study designed to evaluate the safety and efficacy of Nivo combined with neoadjuvant chemotherapy in ESCC. The eligibility criteria were histologically proven ESCC staged as cT1N1-3M0 or cT2-3N0-3M0 (8th UICC TNM classification), age 20-75 years, performance status (PS) ≤1, and no prior cancer therapy. The primary endpoint was the incidence of dose-limiting toxicity (DLT) from the initial dose to postoperative day 30. The secondary endpoints included adverse events during the perioperative period and at 30 days and the objective response rate, R0 resection rate, histopathological complete response rate, and completion rate of the protocol treatment including planned chemotherapy as below followed by R0 resection. Among five study cohorts, patients in cohort E were planned to receive four courses of FLOT+Nivo–5-FU (2600 mg/m2), l-LV (200 mg/m2), L-OHP (85 mg/m2), DTX (50 mg/m2), and Nivo (240 mg)–on day 1 every 2 weeks. Results: Of the 12 patients enrolled in cohort E (median age [range]: 64.5 [53-71] years, PS 0/1: 12/0, clinical stage I/II/III/IVA: 4/5/3/0), 4 developed DLT (grade 3 mucositis, erythema multiforme, and pneumonitis, n=1 each; grade 5 pneumonitis, n=1), which was within the prespecified range of safety (n ≤ 4). Other grades≥3 adverse events were neutropenia (n=7), leukopenia (n=6), fever, fatigue, febrile neutropenia, rash, elevated amylase, elevated hepatic enzyme, hypotension, and thrombocytopenia (n=1 each) during FLOT + Nivo, and anastomotic leakage (n=1) during the postoperative period. One patient discontinued FLOT + Nivo due to DLT of erythema multiforme, eleven patients (91.7%) completed the protocol treatment and R0 resection rate achieved 91.7% (11/12). In cohort E, the objective response rate in patients with measurable lesion was 0% (0/4). However, 5 patients (41.7%) achieved a pathological complete response, and 6 (50.0%) achieved a pathological complete response in primary tumors among 12 patients. Conclusions: Neoadjuvant FLOT + Nivo followed by surgery for locally advanced ESCC was tolerated and showed promising efficacy. Clinical trial information: NCT03914443 .

An online rectal cancer tumoroid biorepository: A resource to facilitate multimodal data integration.

159 Background: Advancing genetic and computational technologies have increased the complexity and quantity of data available in the field of rectal cancer research. As such, there is a need for a centralized source of data to aid and organize current research efforts. To this end, our team has created a unique online biorepository of rectal cancer tumoroids which may serve as a resource for a community of researchers. Methods: The rectal cancer tumoroid biorepository was created in cBioPortal in 2015. Organoids were derived from patient tumor samples (tumoroids). These samples represented multiple treatment timepoints and included primary, recurrent, and metastatic tumors. These tumoroids were further analyzed by various assays such as MSK-IMPACT and IC50 (to fluorouracil, FOLFOX, and FOLFIRI) to obtain patient-specific genomic and chemosensitivity data. A tumoroid profile was then created in cBioPortal for each sample. Clinical information was collected by chart review and annotated into the tumoroid profiles using the unique features of cBioPortal. These included interactive filters and graphical depictions of patient demographics, clinical and pathologic staging, treatment course, clinical response, overall survival, and disease-free survival. Results were organized in an intuitive visual display for convenient analysis. Novel features such as chemosensitivity plots and an interactive patient timeline were incorporated as well. Results: In total, 401 rectal cancer tumoroids have been derived from 177 unique patients. Approximately 32% of the tumoroids were from patients 50 years or younger, and 63% of patients have a treatment naïve sample in our repository. Ten percent of tumoroids were derived from T1-T2 tumors, 56% from T3 tumors, and 17% from T4 tumors. Additionally, 14% of tumoroids were derived from primary tumor recurrences while 6% were derived from metastases. Of the 78% of tumoroids with completely annotated clinical data, 8% were MSI-H, 11% were clinical complete responders, and 5.5% were pathologic complete responders. Lastly, complete IC50 data with clinical correlates has been established for 20% of tumoroids. These data show that tumoroids with a high sensitivity to chemotherapy (FOLFOX) correlated with a 3.3-fold increase in clinical complete response rates in the corresponding patients (p=0.0263). Conclusions: Integrating histopathological, clinicogenomic, and tumoroid response data, this expanding online resource provides a platform to identify valid biomarkers for patient treatment response. This publicly available biorepository built within cBioPortal is intuitive and flexible to accommodate and organize a wide range of data and has the potential to serve as an important resource in rectal cancer research.

As a Transitional Host, Weed Solanum nigrum L. Increases the Population Base of Root-Knot Nematode Meloidogyne enterolobii for the Next Season

The aim of this study was to determine the status of weed Solanum nigrum L. as a transitional host for Meloidogyne enterolobii and its effect on the population base of the nematodes in the next season. The nematode species infecting S. nigrum L. in a fallow field was identified by morphological identification and molecular diagnosis, and parasitic characteristics of the nematodes in S. nigrum L., including development of the nematode in S. nigrum L., the histopathological response of S. nigrum L. to M. enterolobii, and the host suitability of S. nigrum L., were studied. The M. enterolobii soil population density was evaluated before and after S. nigrum L. planting. Species identification revealed that it was M. enterolobii infection. Developmental observation indicated that juveniles of M. enterolobii developed fast in S. nigrum L., establishing feeding sites by 5 days after inoculation (DAI) and forming obvious egg masses on the root at 25 DAI. Histopathological observation showed the typical susceptible response of S. nigrum L., including giant cells with thick cell walls, uniformly dense cytoplasm, and less vacuolation, mainly inside the vascular cylinder. Host suitability assays suggested that S. nigrum L. is a good host for M. enterolobii with an average reproduction factor (RF) of 48.04 ± 14.71. Population densities assays revealed that S. nigrum L. increased the population density of M. enterolobii for two consecutive years from 0.48 ± 0.25 and 0.53 ± 0.31 J2/cm3 to 1.33 ± 0.16 and 1.56 ± 0.43 J2/cm3 of soil. These results indicated that M. enterolobii could reproduce well by infecting S. nigrum L. during the fallow season, and it increased the population base of M. enterolobii to the next season during vegetable production, which suggested a novel direction for the control of root-knot nematodes by controlling weeds as transitional hosts of M. enterolobii in the fallow season.

Histopathological pulp response of teeth capped with calcium aluminate cement and biodentine: Experimental study on rodents

Histopathological pulp response of teeth capped with calcium aluminate cement and biodentine: Experimental study on rodents

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Comparative histopathology of three Serotypes of live infectious bronchitis vaccine (IB88 – 4/91 – H120) in broiler chickens

Infectious bronchitis in birds, caused by a coronavirus, is a highly contagious viral disease that causes economic losses in the poultry industry worldwide. It affects the respiratory, urinary, and genital tracts, and control and prevention are focused on vaccination and biosecurity measures. This study compares histopathological lesions caused by IB88, H120, and IB4-91 vaccines in broiler chickens aged 1 to 5 days. One hundred Ross 308 chickens were divided into four groups: group 1 received the IB4-91 vaccine, group 2 was administered the H120 vaccine, group 3 received the IB88 vaccine, and group 4 served as the control group. Over a period of five days, starting from the second day, five chickens from each group were randomly selected and euthanized. Histopathological samples were collected from the trachea, lungs, and kidneys, processed into slides, and examined under an optical microscope for comparative analysis. When comparing the control and vaccinated groups, there were significant differences regarding histopathological indicators. These included hyperemia and infiltration of inflammatory cells in the kidney, lung hyperemia, infiltration of inflammatory cells, necrosis of respiratory epithelium, and hyperplasia of tracheal mucous cells. Differences were noted between the IB4-91 and H120 groups regarding inflammatory cell infiltration, respiratory epithelium necrosis, tracheal mucous cell hyperplasia, and renal hyperemia. Similarly, variations were observed between the IB88 and H120 groups regarding respiratory epithelium necrosis and tracheal inflammatory cell infiltration. Furthermore, differences were identified in tracheal mucosal hyperplasia and renal hyperemia between the IB4-91 and IB88 groups. These findings highlight distinct histopathological responses induced by different vaccines in broiler chickens and emphasize the importance of vaccine selection in poultry health management.

The role of FDG PET/CT radiomics in the prediction of pathological response to neoadjuvant treatment in patients with esophageal cancer.

Attainment of a complete histopathological response following neoadjuvant therapy has been associated with favorable long-term survival outcomes in esophageal cancer patients. We investigated the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) radiomic features to predict the pathological response to neoadjuvant treatment in patients with esophageal cancer. A retrospective review of medical records of patients with locally advanced resectable esophageal or esophagogastric junctional cancers. Included patients had a baseline FDG PET/CT scan and underwent Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) protocol followed by surgery. Four demographic variables and 107 PET radiomic features were extracted and analyzed using univariate and multivariate analyses to predict response to neoadjuvant therapy. Overall, 53 FDG-avid primary esophageal cancer lesions were segmented and radiomic features were extracted. Seventeen radiomic features and 2 non-radiomics variables were found to exhibit significant differences between neoadjuvant therapy responders and non-responders. An unsupervised hierarchical clustering analysis using these 19 variables classified patients in a manner significantly associated with response to neoadjuvant treatment (p < 0.01). Our findings highlight the potential of FDG PET/CT radiomic features as a predictor for the response to neoadjuvant therapy in esophageal cancer patients. The combination of these radiomic features with select non-radiomic variables provides a model for stratifying patients based on their likelihood to respond to neoadjuvant treatment.

Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

Assessment of Predictive Factors for Response to Neoadjuvant Chemotherapy in Breast Cancer

Objectives The early identification of breast cancer patients who will not respond to neoadjuvant chemotherapy is valuable for timely change in management strategies. Reliable clinical and pathological markers predictive of response to treatment have considerable potential for practical clinical use. Our longitudinal study aimed to assess clinical, pathological, and immunohistological factors predictive of chemotherapy response. Material and Methods Thirty Five patients of breast cancer underwent six cycles of Taxotere, Adriamycin, and Cyclophosphamide (TAC) based neoadjuvant chemotherapy (Docetaxel 75 mg/m2, Doxorubicin 50 mg/m2 or Epirubicin 100 mg/m2 and Cyclophosphamide 500 mg/m2) every three weeks followed by surgery. Histopathological response was assessed after surgery. At a follow up of 12 months, association between factors was tested with Fisher exact test, survival analysis was done with Kaplan Meier analysis and significance was tested by log rank test. Results Five patients out of 35 had pathological complete response (pCR). 14.8% of all T4 disease (P = 0.043) and 22.7% of all Estrogen receptor (ER) negative patients had pCR (P = 0.025). Among all patients showing pCR, four patients (80%) had Grade III tumors (P = 0.018) while all five patients had high Ki67 index (P = 0.032). At 12 months, the mean estimated overall survival came out to be 11.6 months. Mean estimated disease free survival was less for patients with pCR (7.2 months) vs. partial response (10.1 months) (P = 0.44). Conclusion Our study concluded that tumors with larger size, higher stage, higher grade, ER negativity and higher proliferation index had better response to chemotherapy but these tumors also had a trend towards early relapse.

Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-β in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

Lepra Reactions: Mimickers and Mirror to Unmask Complex Cases of Leprosy

Abstract Leprosy is a silent disease with protean manifestations, especially during lepra reactions (LRs). Cases with atypical leprosy or LR simulate a number of conditions misdiagnosed frequently. Here, three classical cases of leprosy are reported for their complex presentation. Leprosy was hidden in Case 1 due to co-existing diabetes. COVID vaccination induced LR unmasked all leprosy lesions, which were extensive, large, bizarre and spreading to various immune zones. Case 2 presented with high-grade fever, tachycardia, generalized erythema and body aches. A detailed workup unveiled his leprosy with a rare presentation of Type 1 lepra reaction (T1LR) with erythroderma and severe systemic symptoms. Case 3 mimicked sarcoidosis and lupus erythematosus (LE) on routine workup. She had facial lesions in the malar area, photosensitivity, joint pains, raised angiotensin-converting enzyme (ACE) levels and positive anti-nuclear antibodies. Peri-appendageal granulomas on histopathology and therapeutic response to multidrug therapy helped in the early diagnosis of leprosy.

Identification and characterization of a highly virulent Citrobacter freundii isolate and its activation on immune responses in largemouth bass (Micropterus salmoides)

Citrobacter freundii, a common pathogen of freshwater fish, causes significant commercial losses to the global fish farming industry. In the present study, a highly pathogenic C. freundii strain was isolated and identified from largemouth bass (Micropterus salmoides). The pathogenicity and antibiotic sensitivity of the C. freundii strain were evaluated, and the histopathology and host immune response of largemouth bass infected with C. freundii were investigated. The results showed that C. freundii was the pathogen causing disease outbreaks in largemouth bass, and the infected fish showed typical signs of acute hemorrhages and visceral enlargement. Antimicrobial susceptibility testing showed that the C. freundii strain was resistant to Kanamycin, Medimycin, Clindamycin, Penicillin, Oxacillin, Ampicillin, Cephalexin, Cefazolin, Cefradine and Vancomycin. Histopathological analysis showed different pathological changes in major tissues of diseased fish. In addition, humoral immune factors such as superoxide dismutase (SOD), catalase (CAT) and lysozyme (LZM) were used as serum indicators to evaluate the immune response of largemouth bass after infection. Quantitative real-time PCR (qRT-PCR) was performed to investigate the expression pattern of immune-related genes (CXCR1, IL-8, IRF7, IgM, CD40, IFN-γ, IL-1β, Hep1, and Hep2) in liver, spleen, and head kidney tissues, which demonstrated a strong immune response induced by C. freundii infection in largemouth bass. The present study provides insights into the pathogenic mechanism of C. freundii and immune response in largemouth bass, promoting the prevention and treatment of diseases caused by C. freundii infection.

Syndrome of liver depression and spleen deficiency is a primary TCM syndrome of response to entecavir + FuZheng HuaYu in patients with HBV-related liver fibrosis

ObjectiveAlthough clinical studies have found that Chinese patent medicine FuZheng HuaYu tablet/capsule can promote the reversal of HBV-related liver fibrosis, not all sufferers have histopathological responses. This study aims to explore the correlation between traditional Chinese medicine (TCM) syndromes and response to entecavir + FuZheng HuaYu (ETV + FZHY) in patients with HBV-related liver fibrosis. MethodsThis a multi-center cross-sectional study. According to the different treatment strategies that sufferers have ever received, a total of 437 cases were included and divided into ETV + FZHY group and ETV + placebo group. And based on the relevant efficacy determination criteria, the two groups were subdivided into efficacy responders and non-responders. Then, TCM clinical questionnaire information of these patients were collected for subsequent analysis to acquire relevant syndrome elements and TCM syndromes. ResultsNo matter what group was, the first three frequency of TCM pathological position in efficacy responders were as follows: Liver > Spleen > Stomach (TCM concepts). As for the ETV + FZHY group, the first three frequency of pathological nature was ranked as Qi deficiency > Dampness > Heat. Compared with the non-responders, the frequency of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation was significantly increased in the efficacy responders (P < 0.05). In terms of TCM syndromes, the frequency increase of Syndrome of liver depression and spleen deficiency (LDSD), in the efficacy responders, changed more obviously than the non-responders (Chi2 = 6.32, P = 0.0006). ConclusionsTCM syndrome elements of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation were closely associated with efficacy responders with HBV-related liver fibrosis in the ETV + FZHY group. Moreover, LDSD was a primary TCM syndrome in these responders.

Diffusion-weighted imaging for determining response to neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis

ObjectivesTo determine the role of diffusion-weighted imaging (DWI) for predicting response to neoadjuvant therapy (NAT) in pancreatic cancer.Materials and methodsMEDLINE, EMBASE, and Cochrane Library databases were searched for studies evaluating the performance of apparent diffusion coefficient (ADC) to assess response to NAT. Data extracted included ADC pre- and post-NAT, for predicting response as defined by imaging, histopathology, or clinical reference standards. ADC values were compared with standardized mean differences. Risk of bias was assessed using the Quality Assessment of Diagnostic Studies (QUADAS-2).ResultsOf 337 studies, 7 were included in the analysis (161 patients). ADC values reported for the pre- and post-NAT assessments overlapped between responders and non-responders. One study reported inability of ADC increase after NAT for distinguishing responders and non-responders. A correlation with histopathological response was reported for pre- and post-NAT ADC in 4 studies. DWI’s diagnostic performance was reported to be high in three studies, with a 91.6–100% sensitivity and 62.5–94.7% specificity. Finally, heterogeneity and high risk of bias were identified across studies, affecting the domains of patient selection, index test, reference standard, and flow and timing.ConclusionDWI might be useful for determining response to NAT in pancreatic cancer. However, there are still too few studies on this matter, which are also heterogeneous and at high risk for bias. Further studies with standardized procedures for data acquisition and accurate reference standards are needed.Clinical relevance statementDiffusion-weighted MRI might be useful for assessing response to neoadjuvant therapy in pancreatic cancer. However, further studies with robust data are needed to provide specific recommendations for clinical practice.Key Points•The role of DWI with ADC measurements for assessing response to neoadjuvant therapy in pancreatic cancer is still unclear.•Pre- and post-neoadjuvant therapy ADC values overlap between responders and non-responders.•DWI has a reported high diagnostic performance for determining response when using histopathological or clinical reference standards; however, studies are still few and at high risk for bias.

214 Angiolymphoid hyperplasia with eosinophilia and kimura disease: a case of clinical and histopathological discrepancy and response to dupilumab

214 Angiolymphoid hyperplasia with eosinophilia and kimura disease: a case of clinical and histopathological discrepancy and response to dupilumab

Toxicity of TPhP on the gills and intestines of zebrafish from the perspectives of histopathology, oxidative stress and immune response

As an organophosphate ester (OPE), triphenyl phosphate (TPhP) has been frequently detected in aquatic environments, and its environmental risk has been widely studied. The gills and intestines are the most important part of the mucosal immune barrier in fish as the first line of defense against the invasion of harmful substances. TPhP is more abundant in the gill and intestine of fish. However, knowledge of the toxic effects and potential mechanisms of TPhP on the intestine and gill is limited. Herein, the adverse effects of TPhP (0.01, 0.1 and 1 mg/L) on the gills and intestines of zebrafish after 75 days of exposure were investigated from the perspectives of histology, oxidative stress and immune level. The histological results of exposed zebrafish showed that TPhP caused significant damage to gills and intestines. TPhP significantly increased the activities of the antioxidant enzymes catalase (CAT) and glutathione s-transferase (GST), inducing oxidative damage to lipids, proteins, and DNA. Meanwhile, the immune function of the gills and intestines was significantly influenced by TPhP, as evidenced by the upregulation of the expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6), upregulation of the content of complement 3 (C3) and complement 4 (C4), and downregulation of the activity of lysozyme (LZM) and the content of immunoglobulin M (IgM). Oxidative stress and the immune response were more severe in the gills. These findings indicate that TPhP, a typical OPE, caused tissue damage in aquatic organisms by inducing oxidative stress and immune damage and has strong environmental toxicity.

Development of Novel Models of Aggressive Variants of Castration-resistant Prostate Cancer

BackgroundGenomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (eg, neuroendocrine prostate cancer [NEPC], PCa with DNA damage response [DDR] alterations, or PCa resistant to androgen receptor pathway inhibitors [ARPIs]). Development of novel therapies relies on the availability of relevant preclinical models. ObjectiveTo develop new preclinical models (patient-derived xenograft [PDX], PDX-derived organoid [PDXO], and patient-derived organoid [PDO]) representative of the most aggressive variants of PCa and to develop a new drug evaluation strategy. Design, setting, and participantsNEPC (n = 5), DDR (n = 7), and microsatellite instability (MSI)-high (n = 1) PDXs were established from 51 patients with metastatic PCa; PDXOs (n = 16) and PDOs (n = 6) were developed to perform drug screening. Histopathology and treatment response were characterized. Molecular profiling was performed by whole-exome sequencing (WES; n = 13), RNA sequencing (RNA-seq; n = 13), and single-cell RNA-seq (n = 14). WES and RNA-seq data from patient tumors were compared with the models. Outcome measurements and statistical analysisRelationships with outcome were analyzed using the multivariable chi-square test and the tumor growth inhibition test. Results and limitationsOur PDXs captured both common and rare molecular phenotypes and their molecular drivers, including alterations of BRCA2, CDK12, MSI-high status, and NEPC. RNA-seq profiling demonstrated broad representation of PCa subtypes. Single-cell RNA-seq indicates that PDXs reproduce cellular and molecular intratumor heterogeneity. WES of matched patient tumors showed preservation of most genetic driver alterations. PDXOs and PDOs preserve drug sensitivity of the matched tissue and can be used to determine drug sensitivity. ConclusionsOur models reproduce the phenotypic and genomic features of both common and aggressive PCa variants and capture their molecular heterogeneity. Successfully developed aggressive-variant PCa preclinical models provide an important tool for predicting tumor response to anticancer therapy and studying resistance mechanisms. Patient summaryIn this report, we looked at the outcomes of preclinical models from patients with metastatic prostate cancer enrolled in the MATCH-R trial (NCT02517892).

Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma Using Image-Guided Clip Placement.

Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington)to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor.

MRI Tumor Regression Grade Combined with T2-Weighted Volumetry May Predict Histopathological Response in Locally Advanced Rectal Cancer following Neoadjuvant Chemoradiotherapy-A New Scoring System Proposal.

Modern studies focus on the discovery of innovative methods to improve the value of post-treatment magnetic resonance imaging (MRI) in the prediction of pathological responses to preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). The aim of this study was to assess the potential benefits of combining magnetic resonance tumor regression grade (mrTRG) with T2-weighted volumetry in the prediction of pathological responses to nCRT in LARC. This was a cohort study conducted on patients with histopathologically confirmed LARC in a period from 2020 to 2022. After histopathological verification, all patients underwent initial MRI studies, while the follow-up MRI was performed after nCRT. Tumor characteristics, MRI estimated tumor regression grade (mrTRG) and tumor volumetry were evaluated both initially and at follow-up. All patients were classified into responders and non-responders according to pathological tumor regression grade (pTRG) and mrTRG. A total of 71 patients, mostly male (66.2%) were included in the study. The median tumor volume reduction rate was significantly higher in nCRT-responders compared to non-responders (79.9% vs. 63.3%) (p = 0.003). Based on ROC analysis, optimal cut-off value for tumor volume reduction rate was determined with an area under the curve (AUC) value of 0.724 (p = 0.003). Using the tumor volume reduction rate ≥75% with the addition of response to nCRT according to mrTRG, a new scoring system for prediction of pTRG to preoperative nCRT in LARC was developed. Diagnostic performance of prediction score was tested and the sensitivity, PPV, specificity, and NPV were 81.8%, 56.3%, 71.4%, and 89.7%, respectively. The combination of mrTRG and T2-weighted volumetry increases the MRI-based prediction of pTRG to preoperative nCRT in LARC. The proposed scoring system could aid in distinguishing responders to nCRT, as these patients could benefit from organ-preserving treatment and a "watch and wait" strategy.