Grade Necrosis Research Articles

Clinicopathologic characteristics of ductal carcinoma in situ and risk of subsequent invasive breast cancer: a multicenter, population-based cohort study.

To study the association between clinicopathologic characteristics of ductal carcinoma in situ (DCIS) and risk of subsequent invasive breast cancer (IBC). We conducted a case-control study nested in a multicenter, population-based cohort of 8175 women aged ≥ 18years with DCIS diagnosed between 1987 and 2016 and followed for a median duration of 83months. Cases (n = 497) were women with a first diagnosis of DCIS who developed a subsequent IBC ≥ 6months later; controls (2/case; n = 959) were matched to cases on age at and calendar year of DCIS diagnosis. Univariable and multivariable conditional logistic regression models were used to examine the associations between the DCIS characteristics of interest (non-screen detection of DCIS, tumor size, positive margins, grade of DCIS, necrosis, architectural pattern, microcalcification, and estrogenreceptor (ER), progesteronereceptor(PR), and human epidermal growth factor receptor 2 (HER2) status) and risk of IBC. In the total study population, the associations were largely null. In subgroup analyses, there were strong position associations with punctate necrosis (pre/perimenopausal women), detection by physical exam (postmenopausal women), architectural patterns other than the main types (breast-conserving surgery [BCS]), and DCIS margins (ipsilateral cases), and inverse associations with HER2 positivity (BCS) and microcalcification (mastectomy); however, the associated confidence intervals were mostly very wide. The results of this study provide limited support for associations of the DCIS clinicopathologic characteristics studied here and risk of IBC.

The Effect of Local Papaverine Use in an Experimental High-Risk Colonic Anastomosis Model: Reduced Inflammatory Findings and Less Necrosis.

Objectives: To assess the impact of topical papaverine administration in complete and incomplete colonic anastomosis, by examining bursting pressure, hydroxyproline concentration, collagen content, inflammation levels, inflammatory cell infiltration, neoangiogenesis, and necrosis grades. Methods: We performed an experimental study on rats, in which they were divided into the following 4 groups of 16 subjects each. Group 1 [complete anastomosis (CA) without papaverine (CA -P) group], Group 2 [CA with papaverine (CA +P) group], Group 3 [incomplete anastomosis (ICA) without papaverine (ICA -P) group], and Group 4 [ICA with papaverine (ICA +P) group]. Results: The lymphocyte infiltration score of the ICA +P3 (day 3) group was significantly higher compared to the ICA -P3 group (p = 0.018). The median Ehrlich-Hunt score (p = 0.012), inflammation score (p = 0.026), and neutrophil infiltration score (p = 0.041) of the CA +P7 (day 7) group were significantly lower than the corresponding data of the CA -P7 group. Additionally, the necrosis score of the ICA +P7 group was significantly lower than that of the ICA -P7 group (p = 0.014). Conclusions: Data from the current study reveal that, although topical papaverine seems to suppress inflammation in anastomosis tissue and reduce necrosis at 7 days, definite conclusions regarding its impact on anastomotic leak cannot be drawn without further studies investigating anastomotic wound healing and anastomotic leak, preferably with both shorter- and longer-term evaluations.

Spectrum of Ductal Carcinoma In Situ (DCIS) Lesions of the Breast: From Morphology to Molecular Characteristics.

Background Specific molecular characteristics of invasive breast cancer have been linked to an increased risk of early relapse. Similarly, ductal carcinoma in situ (DCIS) displays a comparable molecular profile, although their prevalence and implications are not yet fully understood. Aims and objectives The study design defined a multivariable statistical approach aimed at describing the interplay between the histopathological features of ductal carcinoma in situ (DCIS) and their molecular profile. The objective was to explore the correlations between the histopathological features of DCIS (tumor location, DCIS grade, DCIS type, and presence or absence of comedo necrosis) and various biomarkers like estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2/neu), androgen receptor (AR), and epidermal growth factor receptor (EGFR), in addition to the Ki-67 labeling index. Methods In this retrospective study, we selected and analyzed 100 diagnosed cases of ductal carcinoma in situ (DCIS) to represent various subtypes, grades, and morphological characteristics. A detailed histopathological review and immunohistopathological staining for ER, PR, HER2/neu, AR, EGFR, and Ki-67 were performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Molecular subtyping was done based on the biomarker analysis into luminal A, luminal B, luminal HER2/neu, HER2/neu enriched, and triple-negative subtypes. Statistical analysis was done to examine the correlation between tumor location, histopathological features of ductal carcinoma in situ (DCIS), and the expression of the immunohistochemical markers and the molecular subtypes. Results The majority of cases exhibited positivity for estrogen receptor (ER) and progesterone receptor (PR). A strong association was observed between histopathological features (DCIS grade, type, and comedo necrosis) of DCIS and ER/PR status. Additionally, a significant correlation was found between ductal carcinoma in situ (DCIS) grade and HER2/neu status. However, no association was identified between histopathological features and AR or EGFR status. Contrary to expectations, triple-negative DCIS did not show the most aggressive behavior, whereas HER2/neu-positive tumors, particularly high-grade ones, exhibited more aggressive features. No low-grade cases of luminal HER2/neu and HER2/neu-enriched tumors were found. A higher Ki-67 labeling index was found in cases with grade 3 and solid and comedo architectural types of DCIS, while low-grade tumors had a lower Ki-67 labeling index. Conclusion These findings suggest that hormone pathways play a crucial role in ductal carcinoma in situ (DCIS) progression, but the molecular interactions are complex and extend beyond simple binary associations. The complex relationship between the histopathological features of ductal carcinoma in situ (DCIS) and its hormone receptor status warrants further investigation with a larger sample size to fully understand the underlying mechanisms. The results challenge the expectation that triple-negative DCIS is the most aggressive subtype, highlighting the need for further research into the prognostic significance of different DCIS subtypes.

A single-center experience of the upright proton therapy for skull-base chordomas and chondrosarcomas: Updated results

AimTo access efficacy and safety of the upright proton therapy for the skull-base chordomas and chondrosarcomas. Materials and methodsThe study encompasses single-center experience of proton therapy in chordomas (CA) and chondrosarcomas (CSA) of skull-base localization. We evaluate overall survival, local control and toxicity. Tumor response was assessed in accordance with RANO criteria. Treatment-related toxicity was evaluated with the help of CTCAE v 5.0 scale. ResultsProton therapy in the upright position was utilized for 51pts (patients) with CA-CSA (40 pts with chordoma and 11pts with chondrosarcoma) at the A. Tsyb Medical Radiological Research Center in 2016–2023. Median tumor volume constituted 30 cm3 (IQR (interquartile range) 15–41 cm3). Median total dose was 70 GyRBE. Median number of fractions was 35. Overall survival (OS) at 1-, 2- and 3-year rates reached 98.0 %, 88.6 % and 82.7 %, respectively. Median follow-up time was 36 months. The 1-, 2- and 3-year local control (LC) rates constituted, respectively, 98 %, 78.6 % and 66.3 %. Prior surgery showed statistically significant association with better prognosis (p = 0.023). Brainstem-to-tumor dose coverage compromise became the major pattern of LC failure (p = 0.03). The late radiation toxicity reactions included temporal lobe necrosis grade 2 in 2 pts, xerostomia grade 1 in 1pt, radiation cataract grade 2 in 1pt and persistent headache grade 2 in 4 pts. Severe late toxicity reactions were observed in 2 cases (4 %): 1 myelitis grade 3 and brainstem damage grade 5 in 1pt. ConclusionLocal control was achieved in the majority of patients receiving the scanning-beam upright proton therapy for skull-base CA-CSA. The LC rates after a surgery-radiotherapy combination treatment were higher compared with irradiation alone. Pattern of failure is mostly brainstem-tumor dose compromise. The high OS and LC rates were accompanied by low toxicity incidence. Even in complex case of the skull base CA-CSA upright proton therapy shows promising clinical outcomes.

Up Regulation of Ezrin and Radixin with respect to Grade of Tumors in Breast Cancer Patients

Background: Breast cancer (BC) is one of the main causes of death among women in Iran. Biomarkers involved in promotion and progression of disease is very important in management and control of BC outcomes. In this research, we aim to estimate the expression levels of Ezrin and Radixin, as two important factors in morphogenesis, endocytosis, exocytosis, adherence, and migration of cells, in BC patients and their relationship with pathological factors.
 Methods: One hundred and thirteen BC patients were involved in this research. Relative expression of Ezrin and Radixin genes were estimated with quantitative real-time PCR. Pathological data include the histology, tumor size, grade, lymphovascular invasion and clinical TNM (Tumor, Node, and Metastasis) staging of patients were recorded based on the pathology report and their relationship with relative expression of Ezrin and Radixin were estimated.
 Result: According to result Ezrin were over expressed in tumor samples in comparison to adjacent normal tissue. There is a significant relationship between over expression of Ezrin and Radixin and grade of tumor and necrosis. Also there is a direct relationship between relative expression of Ezrin and Radixin expression.
 Conclusions: These data support the role of Ezrin and Radixin in the biology of breast cancer and additional studies needed that determine the Ezrin and Radixin associated with phenotype and may validate them as markers of cancer progression and as a potential target for cancer therapy.

A Comprehensive Correlation of Clinicopathologic Prognostic Factors in Malignant Adult Renal Tumors: A Single Institutional Study.

To study the clinicopathologic prognostic parameters of malignant adult renal tumors as these have poor over-all survival (OS) and show frequent metastasis. This was a retrospective analysis of the clinical and pathologic features of malignant renal tumors in adult patients from January 2011 to December 2020. All the tumors were studied with respect to age, clinical presentation, tumor type/subtype, histologic grade (WHO/ISUP grading system), TNM stage and presence of necrosis. Correlation of histopathologic features and survival analysis was done using Kaplan-Meier survival curves and Cox-regression analysis. A total of 257 cases were included in the study period including 253 renal cell tumors of which clear cell renal cell carcinoma accounted for 69.3%. The age of the patients ranged from 20 to 87 years (median-52 years). The overall survival significantly reduced with increasing histologic grade, stage, and presence of necrosis. The comparison between the histological subtypes was not statistically significant. Univariate Cox-regression analysis found significant hazard ratio with increasing age, size, histologic grade (G4 vs G1), stage, and presence of necrosis. The correlation of OS with histological subtypes was not significant. Multivariate analysis also showed increased hazard ratio with increasing age, size, grade, and stage. However, the P-value was significant only for age. Clear cell renal cell carcinoma was the commonest type of adult renal tumor. Older age at presentation, larger tumor size, presence of necrosis, and higher histologic grade and stage were associated with poor prognosis in these patients.

Immunohistochemical expression of cytochrome P4A11 (CYP4A11), carbonic anhydrase 9 (CAIX) and Ki67 in renal cell carcinoma; diagnostic relevance and relations to clinicopathological parameters

BackgroundCytochrome P4A11 (CYP4A11) is a member of cytochrome p450 family, which is involved in arachidonic acid metabolism that participates in promoting malignant cell proliferation, progression, and angiogenetic capacity. Carbonic Anhydrase 9 (CAIX) is a transmembrane protein that plays an integral part in regulating hypoxia which affects cancer cell metabolism, proliferation and promotes metastasis. The aim of this study was to evaluate the immunohistochemical expression of CYP4A11, CAIX and ki67 in RCC subtypes in relation to clinicopathological parameters and to evaluate the diagnostic significance of CYP4A11 and CAIX in differentiating renal cell carcinoma (RCC) subtypes. Materials and methodsone hundred primary RCC cases, collected from Pathology Department, Faculty of Medicine, Tanta University and from private laboratories, were evaluated for immunohistochemical expression of CYP4A11, CAIX and ki67. ResultsCYP4A11 was expressed in 59% of RCC; with 91.7% sensitivity and 90% specificity in differentiating clear cell and non-clear cell subtypes. CAIX was expressed in 50% of RCC; with 95% sensitivity, 80% specificity. High expression of CYP4A11 was statistically positively associated with higher tumor grade, high expression of CAIX was statistically positively associated with lower tumor grade and absence of necrosis and high ki67 labeling index was significantly associated with clear cell subtype, larger tumor sizes, higher tumor grade, advanced tumor stage, fat invasion and vascular invasion. ConclusionsCYP4A11 and CAIX can be used as diagnostic markers to differentiate clear cell RCC from other subtypes. CYP4A11 is more diagnostically accurate and specific than CAIX. High expression of CYP4A11, low CAIX expression and high ki67 labeling index were related to features of aggressive tumor behavior.

Histopathological prognostic factors in post NACT ovarian cancers: A retrospective study

Epithelial ovarian carcinoma is the most common type of all the ovarian cancers. The patients with advanced stage are initially treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The high mortality rate is mainly due to advanced stage disease at initial presentation. This a retrospective study carried out in department of pathology at Bhagwan Mahaveer cancer hospital, Jaipur. The retrospective cases data was collected and analyzed from patient records on basis of inclusion and exclusion criteria.: Patients of advanced ovarian cancer with fibrosis grade 3, necrosis grade 2, presence of psammoma bodies, presence of collagen deposition, low Ki67 index, positive ER status were associated with longer DFS (p value= 0.014,0.029,0.033,0.028,0.001 and 0.001 respectively) and OS (P value 0.025,0.005,0.002,0.015,0.001 and 0.001 respectively).We propose that the prognostic histopathological parameters analysed in our study in post NACT patients of ovarian carcinoma should be reported in final histopathological report, as these factors can provide an extra tool for clinicians to optimize patient management and care.

Association of Tumour Necrosis with Histopathological Prognostic Parameters in Oral Squamous Cell Carcinoma

Background- Oral squamous cell carcinoma (OSCC) is the most common cancer in India but to the dismay, it has limited treatment modalities. This is a retrospective study on 50 cases of OSCC to evaluate association of tumour necrosis with histopathological parameters like tumour size, nodal involvement and depth of invasion. Methods- This was a retrospective study in which all resection specimens of OSCC operated over a one year period were included. The tumours were graded and staged according to the WHO classification. Tumour necrosis was graded semi-quantitatively as Grade 0- no necrosis, grade1- focal or <10% of total tumour area, moderate or grade 2- necrosis comprising 10-30% of the tumour area and extensive or grade 3- necrosis >30% of the tumour area. Necrosis grade was categorised into- low (Grade 0 and 1) and high (Grade 2 and 3). The association between tumour necrosis and histopathological parameters was evaluated using the Chi square test. Results- A total of 50 resection specimens were included in the study. Out of 50 cases, 14 (28%), 7 (14%), 21(42%), 8 (16%) were T4, T3, T2 and T1 respectively. 28(56%) cases showed low grade necrosis while 22(44%) cases exhibited high grade necrosis. The grade of necrosis showed significant association with depth of invasion, primary tumour size and grade of tumour. However, no association could be elicited between tumour necrosis and nodal status. Conclusions- Tumour necrosis is an easily recognizable histopathological variable which must be included in routine reporting of OSCCs. A higher grade of tumour necrosis is associated with greater tumour size, grade and depth of invasion.

24-hour normothermic machine perfusion of discarded human liver grafts: Case series single-center study

BackgroundThe persistent shortage of liver allografts contributes to significant waitlist mortality. Normothermic machine perfusion (NMP) has the potential to extend viability and allow liver function evaluation in discarded organs. The main aim of the study was to evaluate the possibility for extended preservation and the potential recovery of non-usable human livers utilizing NMP. Methods6 high-risk human liver grafts that were discarded after national allocation underwent normothermic liver preservation for an extended period of 24 h. Transmedics Organ Care System™ liver perfusion device was used to preserve a donor liver in a functioning, near physiologic state. Parameters of biochemical and synthetic liver function were collected periodically and subsequently analyzed. Liver parenchyma and bile duct biopsies were obtained pre- and 24 h post-NMP. Results4/6 (67%) grafts were DCDs with a median age of 54 (IQR: 42–61) years and median CIT of 262 (IQR: 209–1024) minutes. 5/6 (83%) livers produced a median of 75 ml of bile (Range 55–100) after 24 h of NMP. Lactate dropped to normal levels (<2 mmol/L) for all livers after around 4 h on NMP. The overall cellular architecture, lobular steatosis and necrosis grades were preserved after extended NMP. Biopsies showed improvement of liver parenchyma architecture with reduced inflammation for 2/6 (33%) at the end of the perfusion. ConclusionProlonged NMP for discarded liver grafts can be safely maintained on NMP and may identify certain grafts that are suitable for transplantation. Further studies utilizing NMP with subsequent transplantation would validate this strategy, as well as existing viability markers.

Effect of intestinal obstruction stent combined with neoadjuvant chemotherapy on the pathological characteristics of surgical specimens in patients with complete obstructive colorectal cancer

Effect of intestinal obstruction stent combined with neoadjuvant chemotherapy on the pathological characteristics of surgical specimens in patients with complete obstructive colorectal cancer

Primary tracheobronchial necrosis after esophagectomy: A nationwide multicenter retrospective study in Japan.

The clinical features of postoperative primary tracheobronchial necrosis (P-TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess) remains unclear. This nationwide multicenter retrospective study first investigated the clinical features of P-TBN after esophagectomy for upper aerodigestive tract cancer with a large cohort. As a study of the Japan Broncho-Esophagological Society, a nationwide questionnaire survey was conducted in 67 institutions. The clinical data of 6370 patients who underwent esophagectomy for laryngeal, pharyngeal, and esophageal cancer between 2010 and 2019 were collected. Grades of P-TBN were defined as follows: Grade 1, mucosal necrosis; Grade 2, transmural bronchial wall necrosis without fistula or perforation; Grade 3, transmural bronchial wall necrosis with fistula or perforation. P-TBN was observed in 48 (0.75%) of 6370 patients. The incidences of P-TBN for pharyngo-laryngo-cervical esophagectomy (PLCE; n=1650), total pharyngo-laryngo-esophagectomy (TPLE; n=205), and subtotal esophagectomy (SE; n=4515) were 2.0%, 5.4%, and 0.1%, respectively. The upper mediastinal LN dissection (P=0.016) and the higher level of the tracheal resection (P=0.039) were significantly associated with a higher grade of necrosis in PLCE and TPLE. Overall survival rates were significantly lower in patients with Grade 2 (P=0.009) and Grade 3 (P=0.004) than in those with Grade 1. The incidence of TBN restricted to P-TBN was lower than previously reported. Maintaining the tracheal blood flow is essential to prevent worsening P-TBN, especially in PLCE and TPLE. Our new P-TBN severity grade may predict the outcome of patients with P-TBN.

1034 Radiological Outcomes Following Surgery for Developmental Dysplasia of the Hip

Abstract Aim Developmental dysplasia of the hip (DDH) is a condition affecting newborns, in which abnormal acetabulum development can result in femoral head subluxation or dislocation. This study aims to retrospectively evaluate radiological outcomes of patients with DDH, treated by either closed reduction, open reduction, or open reduction with osteotomy. Method This study included 59 hips of 54 patients with a median age of 19.6 months at the time of surgery. Radiographs were assessed for the International Hip Dysplasia Institute (IHDI) grade of dislocation, acetabular index (AI), centre-edge angle (CEA), Severin classification and avascular necrosis (AVN). Results Median duration of follow up between primary operation and latest available radiograph was 4.9 years. Pre-operatively, 41 hips were IHDI Grade IV, 16 hips were Grade III and two hips were Grade II. Mean pre-operative AI was 37.9°, which decreased to 22.7° at the latest follow up. Mean CEA was 22.9°. 25 hips were found to be Severin class I, eight hips were class II and three hips were class III. Four hips developed Group II AVN and one hip developed Group III. Nine hips required further surgery. Conclusions The study found overall favourable radiological outcomes of treatment of DDH, with minimal differences between each operation. Longer follow up is needed to evaluate time-dependent outcomes such as Severin class and AVN. A patient-reported outcome questionnaire is necessary to provide information on the correlation of radiological outcomes and physical function.

High prevalence of necrotizing myofibers in adult dermatomyositis muscle biopsies.

This study aimed to analyze the presence, grade, and relevance of myofiber necrosis in the muscle tissues of patients with adult dermatomyositis. Second, these parameters were associated with the patients' demographic, clinical, and laboratory data. This was a retrospective study, from 2001 to 2021, which included 89 muscle biopsies of patients with definite dermatomyositis performed at the time of diagnostic investigation. Immunohistochemical analysis was performed on serially frozen muscle sections. The presence and degree of endomysial/perifascicular myofiber necrosis were also analyzed. The degree of necrosis was semi-quantitatively coded as absent/mild, moderate, or severe. The presence or absence of perifascicular atrophy and also perivascular lymphomononuclear infiltration was also evaluated. Muscle biopsies from 89 patients, the majority of whom were Caucasian women, were evaluated. Both perifascicular atrophy and perivascular lymphomononuclear infiltrates were observed in 76 (85.4%) samples. Moderate or intense areas of myofiber necrosis in endomysial/perifascicular areas were found in 30/89 (33.7%) and 14/89 (15.7%) muscle biopsies, respectively, with a predominance of macrophagic infiltrate in relation to lymphomononuclear cells in these regions. The degree of muscle weakness in the limbs (upper and lower) was associated only with areas of intense myofiber necrosis. A high prevalence of myofiber necrosis was observed, which patients resembled the initial clinical feature of patients with immune-mediated necrotizing myopathies. Key Point • A high prevalence of myofiber necrosis was observed in muscle biopsies of patients with dermatomyositis.

Histologic Growth Patterns in Clear Cell Renal Cell Carcinoma Stratify Patients into Survival Risk Groups.

Genomic and morphologic heterogeneity in clear cell renal cell carcinoma (ccRCC) presents a barrier to prognostication and treatment decisions. Data from pathology are used with clinical markers to predict disease progression after nephrectomy. However, determining the risk of cancer recurrence, and survival with metastatic cancer remains challenging. Recently, analysis of histologic growth patterns (HGP) in ccRCC revealed promising associations with survival outcomes. To investigate whether HGPs can be used to predict overall survival (OS) after nephrectomy, we examined 24 HGPs in primary tumors of 147 patients that included 107 patients with metastatic disease. The median number of HGPs per case was 5 and was greater in metastatic and larger tumors. After adjustment for 6 pathologic and demographic variables, HGPs were significantly associated with OS post nephrectomy. Small nests, expansile nests and nests with high nuclear to cytoplasmic ratio were associated with favorable outcomes; while spindled low grade, fused nests/solid sheets, rhabdoid, and sarcomatoid patterns were associated with unfavorable outcomes. A 3-tiered and a 2-tiered risk model were developed based on combinations of HGPs. The models performed equally well as WHO/ISUP nucleolar plus necrosis grade (necrosis grade), and better than WHO/ISUP nucleolar grade alone in predicting OS at the median OS of 6 years. Pairwise correlations between HGPs revealed 2 tumor evolutionary branches that differed in risk of metastatic disease: one with mesenchymal differentiation, and other with epithelial tubulopapillary differentiation. While 44 of 107 (41%) patients with metastatic ccRCC displayed evidence of mesenchymal differentiation, mesenchymal features were only observed in 1 of 40 (3%) patients without evidence of metastatic disease. These findings suggest that HGPs may provide a novel path to refine the estimation of OS after nephrectomy and to determine the molecular basis of tumor evolution.

Morphological Features of Ewing Sarcoma Post-Neoadjuvant Therapy and Their Impact on Prognosis

Objective: To study the effect of chemotherapeutic response on resection specimens and to assess their effect on prognosis.&#x0D; Study Design: Retrospective longitudinal study.&#x0D; Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Peshawar Pakistan, from Jan 2010 to Mar 2018.&#x0D; Methodology: This study included 42 cases of Ewing sarcoma diagnosed, treated and followed at our institute. Various diagnostic parameters were noted and were assessed for their impact on two-year overall survival, development of distant metastasis, recurrence and cancer-related death.&#x0D; Results: This study included 28 males and 14 females. The majority involved long bones followed by the axial skeleton and soft tissue. Nine cases (9) were confirmed by molecular testing. On the post-neoadjuvant chemotherapy resection specimens, 45% cases had Huvos grade I necrosis, 17% had grade-II, 12% had grade-III and 26% cases had Huvos grade-IV necrosis. Increasing Huvos grade was associated with improved disease-free survival (21%, 43% and 69% for grades-I, II and III/IV respectively). The site and size did not significantly affect the development of recurrence, development of metastasis, or twoyear survival (p&gt;0.05).&#x0D; Conclusion: Meticulous assessment of post neoadjuvant resection specimens for necrosis provides helpful information about the prognostic outcome. Increasing grade of tumour necrosis was associated with increasing disease-free survival. The response to chemotherapy in our study population was worse than Western data, which may be linked to a variety of factors.

Transplantation of SDF-1α-loaded liver extracellular matrix repopulated with autologous cells attenuated liver fibrosis in a rat model

Cell-based therapy and tissue engineering are promising substitutes for liver transplantation to cure end-stage liver disorders. However, the limited sources for healthy and functional cells and poor engraftment rate are main challenges to the cell-based therapy approach. On the other hand, feasibility of production and size of bioengineered tissues are primary bottlenecks in tissue engineering. Here, we induce regeneration in a rat fibrotic liver model by transplanting a natural bioengineered scaffold with a native microenvironment repopulated with autologous stem/progenitor cells. In the main experimental group, a 1 mm3 stromal derived factor-1α (SDF-1α; S) loaded scaffold from decellularized liver extracellular matrix (LEM) was transplanted (Tx) into a fibrotic liver and the endogenous stem/progenitor cells were mobilized via granulocyte colony stimulating factor (G-CSF; G) therapy. Four weeks after transplantation, changes in liver fibrosis and necrosis, efficacy of cell engraftment and differentiation, vasculogenesis, and liver function recovery were assessed in this (LEM-TxSG) group and compared to the other groups. We found significant reduction in liver fibrosis stage in the LEM-TxSG, LEM-TxS and LEM-TxG groups compared to the control (fibrotic) group. Liver necrosis grade, and alanine transaminase (ALT) and aspartate transaminase (AST) levels dramatically reduced in all experimental groups compared to the control group. However, the number of engrafted cells into the transplanted scaffold and ratio of albumin (Alb) positive cells per total incorporated cells were considerably higher in the LEM-TxSG group compared to the LEM-Tx, LEM-TxS and LEM-TxG groups. Serum Alb levels increased in the LEM-Tx, LEM-TxS, and LEM-TxG groups, and was highest in the LEM-TxSG group, which was significantly more than the fibrotic group. Small vessel formation in the LEM-TxSG group was significantly higher than the LEM-Tx and LEM-TxS groups. Totally, these findings support application of the in vivo tissue engineering approach as a possible novel therapeutic strategy for liver fibrosis.

Clinical and radiological outcomes of Salter versus Pemberton osteotomies in the management of developmental dysplasia of the hip: A retrospective comparative study.

The aim of this study was to investigate whether there is a relationship between Salter and Pemberton pelvic osteotomies and avascular necrosis of femoral head in the management of developmental dysplasia of the hip (DDH). This retrospective study included 69 hips of 52 patients aged between 12-36 months, diagnosed as DDH who had undergone either Salter or Pemberton pelvic osteotomy with Smith Petersen approach. There were 35 patients in Salter Pelvic Osteotomy and 34 patients in Pemberton Pelvic Osteotomy groups. Before the treatment of DDH, Tönnis classification was used, preoperative and 24th month postoperative Acetabular Index (AI) angles were measured. Kalamchi-MacEwen grades of avascular necrosis were determined in terms of presence of avascular necrosis of the femoral head. There were no significant differences between two osteotomy groups at the end of mid-term follow up in terms of the radiological parameters and avascular necrosis of femoral head. However it was found that the increased avascular necrosis incidence was significantly associated with Tönnis grade 4 hips. Salter and Pemberton osteotomies can be both used safely in the treatment of DDH regarding their effect on the femoral head. Level III, Therapeutic Study.

Correlation between expression of immunohistochemical markers and morphology in lung neuroendocrine neoplasms

lung neuroendocrine neoplasms embrace rather heterogeneous and rare malignancies which are usually characterized by nonspecific, “blurred” clinical signs thus complicating correct diagnosis or seriously delays it. Pulmonary neuroendocrine neoplasms accurate diagnostics and classification need to be improved. Histological examination should be supplemented by immunohistochemical tests to verify the neuroendocrine component, assess proliferative index of tumor cells, and confirm its bronchopulmonary origin. Immunohistochemistry is especially important in case of small or crushed biopsies, which account more than 50% of all specimens in lungs neuroendocrine neoplasms. Modern classification of lung neuroendocrine neoplasms and their grading are based on morphological criteria. Immunohistochemical markers expression is quite variable in different histological subtypes of bronchopulmonary neuroendocrine neoplasms, often data are descriptive, and correlation with morphology is studied insufficiently. The aim of this study was to define any significant correlation between different immunohistochemical markers expression, necrosis, proliferative index (Ki-67 ratio), and tumor grade in broncho-pulmonary neuroendocrine neoplasms. Histological blocks of lung neuroendocrine neoplasms from 113 unique patients (36 resections and 77 biopsies (54.5% of biopsies appeared to be small or crushed) were used in this study. The sample comprised 91 male and 22 female patients; the mean age was 59.2, CI 95% (56.9–61.4) years (from 19 to 77 years). Histological examination (including neuroendocrine morphology, necrosis, and grade) was provided in all cases. Also, immunohistochemistry, using Chr A, Syn, CD56, TTF-1, CK7, and Ki-67 before chemotherapy was performed. All morphological and immunohistochemical data were assessed by two different independent pathologists without the access to patient’s clinical data. All the observations were classified based on 2021 WHO Thoracic Tumors Classification. The sample was censored. We used nonparametric statistics (Spearman’s rank correlation) for this study. In was found that Chr A expression strongly (p&lt;0.05) correlated with immunohistochemical markers of primary lung malignancies (TTF-1 and CK7) that are mainly expressed in highly and moderately differentiated neuroendocrine neoplasms. Also, positive expression for TTF-1 and CK7 correlated with each other (p&lt;0.01). There was a strong negative correlation (p&lt;0.05) between Chr A staining and necrosis presence and it’s severity; between Chr A expression and tumor cells proliferation (Ki-67 ratio) (p&lt;0.01); and between Chr A labeling and tumor grade (p&lt;0.01). The correlation of immunohistochemical markers expression with necrosis, Ki-67 ratio and tumor grade was significant only for Chr A. All other tested options, for other markers were not statistically significant. It was defined that decrease or loss of Chr A expression reliably indicates tumors progression. Chr A expression can be used as an additional tool for grading of lung neuroendocrine neoplasms.

A conservative approach towards idiopathic chondrolysis of hip: a case report

Chondrolysis of the hip causes pain and a limping as articular cartilage space is gradually lost due to an unknown but suspected inflammatory process. It could be idiopathic or due to another hip condition, such as slipped capital femoral epiphysis. It is a well-known complication of a slipped capital femoral epiphysis, although it can also occur as a result of trauma, septic arthritis, immobilization, or juvenile idiopathic arthritis. Idiopathic chondrolysis of the hip is a disorder that causes the articular cartilage of the hip joint to degrade spontaneously. The most common clinical manifestation is pain at the affected hip joint, which is linked to increasing joint stiffness and a significant loss of range of motion and function. Idiopathic chondrolysis of hip is a rare condition with Incidence around 8.2% percent. In this case report we are presenting a 12-year-old boy came with complaint of pain, stiffness and restricted range of movement at left hip joint followed by trauma. On the basis of physical and investigatory findings, the patient was diagnosed as a case of idiopathic chondrolysis of hip associated with avascular necrosis grade 4 according to Ficat and Arlet classification. Radiological findings were evident of reduced joint space of left hip and slipped capital epiphysis, this is known to be the hallmark finding to confirm the diagnosis of idiopathic chondrolysis of hip. The patient was conservatively managed with non-steroidal anti-inflammatory medicines, vigorous physiotherapy. Chrondolysis is usually managed with bed rest, traction and non-steroidal anti-inflammatory drugs, hence the aim of this case report was to incorporate an elaborate and efficiency of physical Therapy along with medical management to promote the recovery, aid early return to activities of daily living and improve quality of life.