Predictive Factors of Neoadjuvant Chemotherapy Response in Breast Cancer Validated by Three Anatomopathological Scores: Residual Cancer Burden, Chevallier System, and Tumor-Infiltrating Lymphocytes.

INTRODUCTION: The aim of this retrospective, observational, descriptive study was to identify predictors of response to neoadjuvant therapy in breast cancer patients and to validate them using three anatomopathological scores, such as residual cancer burden (RCB) score, Chevallier system, and tumor-infiltrating lymphocytes (TIL) score. MATERIALS AND METHODS: We conducted a study on 88 female patients aged 37 to 78 years with confirmed breast cancer who were indicated for neoadjuvant chemotherapy. We analyzed different individual variables (such as age, menarche, and menopause), clinical/imaging characteristics of the breast tumor and axillary nodes, immunohistochemical biomarkers (such as ER/PR/HER2 and Ki67), and histopathological features (such as subtype and grading) in relation to three anatomopathological scores calculated based on the surgical resection specimen. RESULTS: The percentage of patients who could have benefited from conservative surgery increased from 6% at the time of diagnosis to 20% post-primary systemic therapy (PST). Age under 49 (p = 0.01), premenopausal status (p < 0.01), no special type (NST) (p = 0.04), high Ki67 (p < 0.01), triple-negative breast cancer (TNBC) (p = 0.02) are positive predictive factors of neoadjuvant therapy, while lobular/mixt carcinoma-type (p = 0.04), luminal A (p = 0.01), positive lymph node (p < 0.01), and low differentiation grade (p = 0.01) are negative predictive factors for the response to PST. CONCLUSION: There is a strong correlation between the RCB score and the Chevallier system for quantifying the response to PST, with most predictive factors being confirmed through appropriate statistical analysis for both. TIL score values correlated with only some of the predictors, most likely due to the importance of calculating this score on both biopsy specimens at diagnosis and resection specimens after chemotherapy.

Effects of Acidic Environments on Dental Structures after Bracket Debonding.

Brackets are metallic dental devices that are very often associated with acidic soft drinks such as cola and energy drinks. Acid erosion may affect the bonding between brackets and the enamel surface. The purpose of this study was to investigate the characteristics of brackets' adhesion, in the presence of two different commercially available drinks. Sixty human teeth were divided into six groups and bonded with either resin-modified glass ionomer (RMGIC) or resin composite (CR). A shared bond test (SBS) was evaluated by comparing two control groups with four other categories, in which teeth were immersed in either Coca-ColaTM or Red BullTM energy drink. The debonding between the bracket and enamel was evaluated by SEM. The morphological aspect correlated with SBS results showed the best results for the samples exposed to artificial saliva. The best adhesion resistance to the acid erosion environment was observed in the group of teeth immersed in Red BullTM and with brackets bonded with RMGIC. The debonded structures were also exposed to Coca-ColaTM and Red BullTM to assess, by atomic force microscopy investigation (AFM), the erosive effect on the enamel surface after debonding and after polishing restoration. The results showed a significant increase in surface roughness due to acid erosion. Polishing restoration of the enamel surface significantly reduced the surface roughness that resulted after debonding, and inhibited acid erosion. The roughness values obtained from polished samples after exposure to Coca-ColaTM and Red BullTM were significantly lower in that case than for the debonded structures. Statistical results evaluating roughness showed that Red BullTM has a more erosive effect than Coca-Cola™. This result is supported by the large contact surface that resulted after debonding. In conclusion, the prolonged exposure of the brackets to acidic drinks affected the bonding strength due to erosion propagation into both the enamel-adhesive interface and the bonding layer. The best resistance to acid erosion was obtained by RMGIC.

Mechanical Properties of Orthodontic Cements and Their Behavior in Acidic Environments.

The present research is focused on three different classes of orthodontic cements: resin composites (e.g., BracePaste); resin-modified glass ionomer RMGIC (e.g., Fuji Ortho) and resin cement (e.g., Transbond). Their mechanical properties such as compressive strength, diametral tensile strength and flexural strength were correlated with the samples' microstructures, liquid absorption, and solubility in liquid. The results show that the best compressive (100 MPa) and flexural strength (75 Mpa) was obtained by BracePaste and the best diametral tensile strength was obtained by Transbond (230 MPa). The lowestvalues were obtained by Fuji Ortho RMGIC. The elastic modulus is relatively high around 14 GPa for BracePaste, and Fuji Ortho and Transbond have only 7 GPa. The samples were also subjected to artificial saliva and tested in different acidic environments such as Coca-Cola and Red Bull. Their absorption and solubility were investigated at different times ranging from 1 day to 21 days. Fuji Ortho presents the highest liquid absorption followed by Transbond, the artificial saliva has the best absorption and Red Bull has the lowest absorption. The best resistance to the liquids was obtained by BracePaste in all environments. Coca-Cola presents values four times greater than the ones observed for artificial saliva. Solubility tests show that BracePaste is more soluble in artificial saliva, and Fuji Ortho and Transbond are more soluble in Red Bull and Coca-Cola. Scanning electron microscopy (SEM) images evidenced a compact structure for BracePaste in all environments sustaining the lower liquid absorption values. Fuji Ortho and Transbond present a fissure network allowing the liquid to carry out in-depth penetration of materials. SEM observations are in good agreement with the atomic force microscopy (AFM) results. The surface roughness decreases with the acidity increasing for BracePaste meanwhile it increases with the acidity for Fuji Ortho and Transbond. In conclusion: BracePaste is recommended for long-term orthodontic treatment for patients who regularly consume acidic beverages, Fuji Ortho is recommended for short-term orthodontic treatment for patients who regularly consume acidic beverages and Transbond is recommended for orthodontic treatment over an average time period for patients who do not regularly consume acidic beverages.

PD-L1 Expression in Esophageal and Gastroesophageal Junction Carcinoma, Correlation with the Immune Infiltrate - Preliminary Study.

Background: Although traditional management for esophageal and esogastric cancer has been improved, survival at 5 years is still low, and immunotherapy could be a way to improve it. In addition to the predictive value of the response to immunotherapy, PD-L1 also has a known prognostic value. We aimed to evaluate the immunohistochemical expression of PD-L1, CD8+ T-cell, and CD4/CD25+ T-cell (Tregs) infiltration and their relationship in esophageal and gastroesophageal junction carcinoma. Material and Methods: Endoscopic biopsies were analyzed in 14 patients with esophageal cancer or esogastric junction, before starting the neoadjuvant treatment, hospitalized from the period 2019- to 2021 in the St. Mary's Clinical Hospital, Bucharest. Immunohistochemical tests were performed to investigate the expression of lymphocyte intratumoral infiltrate markers. Results: Of the 14 cases, 13 (93%) were male, and 1 (7%) were female. Histological, 4 cases were adenocarcinomas, and 10 cases were squamous cell carcinomas. 10 cases showed epithelial PD-L1 positivity (78%). Using a quantitative evaluation of PD-L1 we obtained a statistical correlation between the median values of this marker with the expression of CD8. There was obtained a statistical correlation between PD-L1 positivity and low expression of CD4 or CD4+/CD25 T cells. Conclusions: PD-L1 is expressed in tumors with higher CD8+ T cell densities and lower CD4/CD25 positive cells (Tregs), indicating that the good prognosis of PD-L1-positive tumors could be due to the inhibition of CD4 / CD25-positive cells (Tregs) rather than the stimulation of CD8-positive T cells, by an adaptive immune resistance mechanism.

A Single Center Experience in Liver Resection and Ablative Techniques: An Analysis of Six Years.

Introduction: We present our 6-year experience with liver surgery and ablative techniques. Method: An observational retrospective analysis from a prospectively maintained database was performed in our department. All the patients with liver resection, liver resection combined with intraoperative ablative techniques and percutaneous ablative techniques were included from January 1st 2014 to December 31st 2020. Results: There were 249 patients analyzed: 273 patients with liver resection, 12 patients with liver resection combined with intraoperative MWA, 9 patients with open surgery MWA, 12 patients with percutaneous MWA, 1 patient with TACE and MWA, 1 patient with TACE and PEI, 10 patients with TACE, and 2 patients with PEI. Conclusion: Liver disease should be managed in specialized centers which can offer a wide range of therapeutic options. With the improvement of the surgical technique and perioperative care, including optimized postoperative complication management, and carried out by well-trained surgeons, liver surgery can be performed with low mortality and acceptable morbidity.

Gastric Metastasis of Invasive Lobular Breast Carcinoma, a Current Diagnostic and Treatment Challenge - A Review.

Introduction: The predilection of lobular invasive breast cancer metastasis for the stomach is a topic that has succumbed to various assumptions over the time. Background and Aims: Gastric metastasis of lobular breast cancer is unusual and it can be diagnosed after a long period of time from primary tumor diagnosis. The aim of this study was to review current knowledge regarding the current methods of diagnosis and treatment of gastric metastasis of breast cancer. Methods: A systematic literature search was performed in the Pub-Med Medline database using the terms "gastric metastasis of lobular breast cancer" and "gastric metastasis features" to identify articles relevant to gastric metastasis of lobular breast cancer. Results: Several papers have shown that the topic is rarely presented in the form of case presentations or miniseries by summing up sporadic cases. Due to its rarity and metastasis specificity as host type and appearance after latency of lobular breast cancer makes its gastric metastasis considered atypical and occasionally confused with a primary stomach malignancy. The most recent articles present the immunohistochemical diagnostic criteria of this clinical entity and a new therapeutic approach. Conclusion: At patients with gastric metastasis of lobular breast cancer, obtaining pathologic material and biopsies interpretation can be a real challenge for getting a correct pathologic diagnosis, immunohistochemistry gives us definite diagnosis. The introduction of an endoscopic surveillance protocol for patients with lobular breast cancer could be a proposal for the detection of early gastric metastases allowing for appropriate therapy.

Diagnostic challenges in a patient with calciphylaxia - a case report.

Calciphylaxis is a condition with unclear etiopathogeny with vascular calcifications and thrombotic occlusion that lead to necrotic lesions. It is usually described in patients with end-stage renal disease (ESRD), but also in other conditions. The mortality rate is high, due to sepsis and internal organ failure. We present the case of a patient with multiple comorbidities (ESRD, diabetes, hypertension, Mönckeberg's sclerosis) with problems of differential diagnostic due to the necrotic lesions that mislead initially to systemic lupus erythematosus (SLE) with necrotizing vasculitis.

Stevens-Johnsons syndrome or drug-induced lupus - a clinical dilemma: A case report and review of the literature.

Tumor necrosis factor inhibitors are the first biological agents used in the treatment of rheumatoid arthritis (RA) to have yielded satisfactory results in terms of clinical improvement and radiologic progression, but they are also associated with the possibility of occurrence of a number of autoimmune systemic events [drug-induced lupus (DIL), vasculitis, sarcoidosis] and localized adverse events [uveitis, psoriasis, interstitial lung disease, erythema multiforme including the major form Stevens-Johnson syndrome (SJS)]. During treatment with TNF inhibitors, many patients develop positivity for antinuclear, antihistone and anti-double stranded DNA antibodies, though only a minority of patients will develop clinical manifestations and approximately less than 1% will fulfill the classification criteria for systemic lupus erythematosus. Mucocutaneous manifestations are the most frequent manifestations of DIL following treatment with TNF inhibitors, and can be severe and occasionally difficult to differentiate from erythema multiforme/SJS. Stopping the causative drug (the TNF inhibitor) and general supportive measures are usually sufficient in mild forms, but in moderate to severe forms, systemic glucocorticoids and sometimes immunosuppressive drugs are required. The present report presents the case of a patient with rheumatoid arthritis who developed severe recurrent cutaneous reactions and positive autoantibodies during TNF inhibitor treatment, with difficulties in differential diagnosis and treatment. A review of the literature is also presented.

Mutational status of KRAS and MMR genes in a series of colorectal carcinoma cases.

BACKGROUND: The KRAS gene mutation is the most common somatic change in colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of all CRCs, more frequent in early stages. CRCs with MSI present better prognosis, a distinct histopathological aspect and a different response to chemotherapy. Patients with both KRAS wild type and MSI have a reduced risk of dissemination and recurrence. MATERIALS AND METHODS: Our study included formalin-fixed paraffin-embedded tissue samples from 40 patients with metastatic CRCs, aged between 40 and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were analyzed using an indirect bistadial immunohistochemical (IHC) technique with monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Of the 40 tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13. IHC expression of MMR proteins revealed a microsatellite stable status in 35 cases, including 15 cases with mutated KRAS. MSI status was identified in five cases (four with KRAS wild type). All MSI tumors had a poorer histological differentiation and four cases revealed a mucinous phenotype. Eighty percent of the patients with MSI status were older women. CONCLUSIONS: Our study demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS mutations being inversely correlated with MSI status in these tumors. MMR protein deficient CRCs tend to occur in older females, have a poorer differentiation and are frequently associated with KRAS wild type.

Benefits and Disadvantages of Neoadjuvant Radiochemotherapy (RCT) in the Multimodal Therapy of Squamous Esophageal Cancer (ESC).

INTRODUCTION: The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. MATERIAL AND METHOD: Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. RESULTS: 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. CONCLUSION: RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders.

KRAS gene mutations - prognostic factor in colorectal cancer?

The colorectal cancer (CRC) modern therapy is using adjuvant and neoadjuvant companion therapeutic agents, part of them having an anti-angiogenic action. Their benefic effect can be annulated by some gene mutations, which are interfering in signal transduction pathways. One of the more frequent activating mutations is occurring in the KRAS gene. We assessed the KRAS mutations by two molecular methods, in a group of patients with a follow-up until 144 months, aiming to establish eventual correlations between the presence of mutations and the evolution of patients. We tried to appreciate the prognostic value of these mutations. A retrospective study was conducted on 74 patients treated by radical surgery; the surgical specimens were analyzed macroscopically and the histopathological type and degree were established. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and pyrosequencing were performed on paraffin-embedded tumor specimens. Statistical analysis showed significant differences in survival between patients with wild type gene and patients with mutation in codon 13; the same results were also obtained regarding TNM I, II stages or Dukes type A and B cases. However, for the patients in stage IV pTNM, the evolution was slightly better in association with a KRAS mutation than in wild type cases.

PLUNC proteins positivity in patients with chronic rhinosinusitis: a case-control study.

INTRODUCTION: Innate immunity is the first protection against microorganisms. Nowadays, there is a growing interest in innate immune molecule known as palate, lung, nasal epithelial clone (PLUNC). PLUNC is a specific product of the airways, of approximately 25 kDa, encoded by adjacent genes found within a 300 kb region of chromosome 20; these proteins must be detected predominantly in the upper respiratory tract. MATERIALS AND METHODS: We performed a case-control study to investigate the presence of this protein in nasal tissue of patients affected by chronic rhinosinusitis. 59 patients were enrolled (44 cases, 15 controls). We have examined the correlation between the presence of pathology and the PLUNC proteins positivity. RESULTS: 100% of controls have a +++ rated PLUNC proteins positivity, while cases have a lower percentage of positivity. We used χ (2) statistical test to analyze the results of the study and there is a difference statistically significant between cases and controls in PLUNC proteins positivity. CONCLUSIONS: These observations suggest that, in response to agents or chemical factors, nasal mucosal epithelium will react and produce PLUNC proteins. So PLUNC proteins have a protective function on upper airways mucosa, as we can see by evaluating the high positivity in control group.

Littoral cell angioma of the spleen--a surprising cause of anemia.

Littoral cell angioma is a rare tumor of the spleen, usually being considered benign and typically discovered incidentally. There are three different modalities of presentation: tumoral splenomegaly, long-standing iron deficient anemia or thrombocytopenia due to hypersplenism. However, some of its manifestations could generate the suspicion of a lymphoma or other more serious condition. We present the case of a 46-year-old man with splenomegaly and iron deficiency anemia. The tumor affected the whole spleen, which was surgically removed. The histopathological examination, together with immunophenotyping, established the diagnosis. Six months after the procedure, the patient is in very good condition. Several differential diagnoses were discussed, as well as the prognostic factors. The case illustrates a rare cause of anemia and the importance of pathology in uncovering such unusual causes for this.

K-ras gene mutation status in colorectal cancer: comparative analysis of pyrosequencing and PCR-RFLP.

BACKGROUND: In patients with high-stage colorectal carcinomas (CRC), anti-EGFR therapy is known to be effective only in cases with a wild-type K-ras gene status. Different procedures have been proposed for such evaluation. MATERIALS AND METHODS: The mutation status of K-ras gene, codons 12, 13 and 61 was determined in 250 CRC cases using the pyrosequencing assay. In addition, we compared the performance of the pyrosequencing procedure with that of PCR-RFLP in a subset (n=100) of the CRC samples the latter only in codons 12 and 13. RESULTS: Using pyrosequencing, 46.4% of the 250 CRC cases were found mutated. Most mutations were located in codon 12 (36.4% from all cases) and several were located in codon 61 (3.2%). All mutation identified by PCR-RFLP were confirmed by pyrosequencing and, in addition, one more mutated sample was identified in the subset of 100 samples. CONCLUSIONS: Both methods are highly specific and can profitably be used in the molecular diagnosis of colorectal cancer in order to establish the adequate therapy.

Foxp3 and IL17 expression in tumor infiltrating lymphocytes (TIL) and tumor cells - correlated or independent factors?

Tumor infiltrating lymphocytes (TIL), as a microenvironment component were studied in various epithelial tumors, with contradictory results. Recent data about regulatory T-cells (Treg) revealed new explanations for pro- and anti-tumor implications of TIL. Tregs immunoprofile was recently completed with Foxp3 expression. A T-cell fraction (Th) is producing cytokine IL17 and is now considered acting in tumor progression. Our study aimed to analyze immunohistochemically (IHC) Foxp3+ and IL17 expression in resected lung adenocarcinomas, since they could become possible targets in the antitumor immunotherapy. The studied material was represented by paraffin-embedded tumor fragments from 59 patients with TIL identified on HE staining. The antibodies used were Foxp3 and IL17. The statistical analysis used logistical regression on SPSS19 software (Chicago, IL, USA). TIL was usually mild or scarce. A positive statistic correlation resulted between the amounts of TIL in peritumoral and intratumoral location but without correlation to histopathological grading. Foxp3 and IL17 were present in TIL lymphocytes, tumor cells and fibroblasts; IL17 was expressed also in periendothelial cells (PEC). Foxp3 positivity was significantly correlated for lymphocytes÷tumor cells, lymphocytes÷fibroblasts and tumor cells÷fibroblasts, suggesting their concerted action. Tumor cells and lymphocytes Foxp3 expression was inversely correlated with the amount of TIL. Between lymphocytic Foxp3 and PEC IL17, we found a weak negative correlation. The TIL had a quite positive correlation with PEC IL17. In these conditions, Foxp3 could be a mediator of the tumor cells inhibitory aggression upon the immune system and could be used as a molecular target for biological antitumor therapy.

Somatostatinoma of the first jejunal loop in a patient with neurofibromatosis von Recklinghausen and bilateral pheochromocytoma.

Somatostatinoma is a rare neuroendocrine tumor which especially develops in the pancreas. There are few communicated cases about extra-pancreatic localization, having as a particularity the absence of somatostatin hypersecretion syndrome and frequent association with von Recklinghausen neurofibromatosis. We present the case of a 42-year old patient with Von Recklinghausen neurofibromatosis admitted in our clinic with a chronic upper digestive obstruction syndrome. The presence of a first jejunal loop somatostatinoma was an intraoperative surprising diagnosis that imposed jejunal resection and association of complementary specific treatment. Despite the therapeutic correct management, the status of the patient deteriorated very fast, confirming the aggressiveness of this neoplasia.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

Nestin and caveolin-1 in the diagnosis of GISTs.

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal neoplasias of the gastrointestinal tract, typically expressing c-kit (CD117) and CD34. Recently, it was reported that nestin and caveolin-1 are also expressed in some human sarcomas, GISTs included. We performed a retrospective study on formalin fixed, paraffin embedded samples from 81 cases of confirmed GISTs, aiming to characterize their immunohistochemical profile, including nestin and caveolin-1 expressions. Tissue samples were evaluated immunohistochemically for CD117, CD34, nestin and caveolin-1. The patients (M:F 36:45), aged 46 to 84 years, had spindle cell type GISTs in 56.7% of cases, epithelioid in 30.8% and mixed pattern in 12.3%. Immunohistochemically, CD117 was positive in 88.9% of GISTs, CD34 in 85.1%, nestin in 77.7% and caveolin-1 in 71.6% of the tumors. Of nine c-kit negative GISTs, 66.7% expressed nestin, the same as caveolin-1 and 44.5% expressed both nestin and caveolin-1. Statistical analysis using Kendall's and Spearman's tests revealed significant correlations between nestin and caveolin-1 expressions (p=0.024). Our results suggest that nestin and caveolin-1 could be considered sensitive markers in GISTs, together with CD117 and CD34, for diagnostic purposes. Their significant expression in CD117 negative GISTs could represent an immunohistochemical alternative in establishing the diagnosis of these tumors.

Malignant fibrous histiocytoma of larynx with giant cell: case report and histological-clinical considerations.

INTRODUCTION: Malignant fibrous histiocytoma (MFH) is a tumor which has a mesenchymal origin, and an uncertain histogenesis. MFH with giant cell accounts for 3-15% of all malignant fibrous histiocytomas. OBJECTIVE: To explore the histopathology, the diagnosis and the treatment of MFH with giant cell of larynx. PATIENT AND METHODS: We report a case of a glottic MFH at a 59-year-old male, who has been smoking for 30 years, and was hospitalized in June 2008 at Emergency County Hospital of Craiova. RESULTS: The largely-sized tumor was originated in glottic area, upper a left vocal cord, with no paresis. The tumor determined respiratory failure and dysphonia. Patient underwent surgical excision of the tumor after an emergency tracheotomy. The immunohistochemical techniques proved positive for vimentin, smooth muscle actin, CD68, CD34, bcl2, EGFR, S100, Ki67, and negative for CD117, NFT, chromogranin, c-erbB2, CK34betaE12, MNF116, and p53. CONCLUSIONS: Malignant fibrous histiocytomas (MFH) with giant cell of larynx are very rare mesenchymal neoplasm (this case seems the first reported). The diagnosis of MFH of larynx was difficult and the immunohistochemistry could have been helpful.