Histological In Vivo Evaluation of Intense Pulsed Light Technology: Assessing the Safety on Oral Soft and Hard Tissues.

Intense pulsed light (IPL) is used for aesthetic and therapeutic purposes. According to recent literature, utilizing IPL may boost upregulation of anti-inflammatory cytokines, and downregulation of pro-inflammatory cytokines. Concerns have been raised about potential thermal damage to the soft and hard tissues in the oral cavity. Therefore, the aim of this study was to determine the safety of using IPL of various intensities in the tissues of the oral cavity. METHODS: Three adult pigs were included in the trial. The oral cavity was divided into four quadrants and projected with a wide range of IPL settings. Alveolar bone, buccal mucosa, and gingival tissue samples were taken immediately and after 24 h. In each animal, one quadrant of the jaw was left untreated and served as a control. All samples were processed and stained with H&E. RESULTS: Clinical examination showed no evidence of changes in the integrity of the examined tissues. Histological examination of the different tissues did not demonstrate significant thermal damage or changes in the characterization of the cells compared to the control tissues. CONCLUSIONS: The use of IPL in the oral cavity is safe and does not negatively affect the tissues.

Relative Wash-In Rate in Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Prognostic Biomarker for Event-Free Survival in 82 Patients with Osteosarcoma: A Multicenter Study.

BACKGROUND: The decreased perfusion of osteosarcoma in dynamic contrast-enhanced (DCE) MRI, reflecting a good histological response to neoadjuvant chemotherapy, has been described. PURPOSE: In this study, we aim to explore the potential of the relative wash-in rate as a prognostic factor for event-free survival (EFS). METHODS: Skeletal high-grade osteosarcoma patients, treated in two tertiary referral centers between 2005 and 2022, were retrospectively included. The relative wash-in rate (rWIR) was determined with DCE-MRI before, after, or during the second cycle of chemotherapy (pre-resection). A previously determined cut-off was used to categorize patients, where rWIR < 2.3 was considered poor and rWIR ≥ 2.3 a good radiological response. EFS was defined as the time from resection to the first event: local recurrence, new metastases, or tumor-related death. EFS was estimated using Kaplan-Meier's methodology. Multivariate Cox proportional hazard model was used to estimate the effect of histological response and rWIR on EFS, adjusted for traditional prognostic factors. RESULTS: Eighty-two patients (median age: 17 years; IQR: 14-28) were included. The median follow-up duration was 11.8 years (95% CI: 11.0-12.7). During follow-up, 33 events occurred. Poor histological response was not significantly associated with EFS (HR: 1.8; 95% CI: 0.9-3.8), whereas a poor radiological response was associated with a worse EFS (HR: 2.4; 95% CI: 1.1-5.0). In a subpopulation without initial metastases, the binary assessment of rWIR approached statistical significance (HR: 2.3; 95% CI: 1.0-5.2), whereas its continuous evaluation demonstrated a significant association between higher rWIR and improved EFS (HR: 0.7; 95% CI: 0.5-0.9), underlining the effect of response to chemotherapy. The 2- and 5-year EFS for patients with a rWIR ≥ 2.3 were 85% and 75% versus 55% and 50% for patients with a rWIR < 2.3. CONCLUSION: The predicted poor chemo response with MRI (rWIR < 2.3) is associated with shorter EFS even when adjusted for known clinical covariates and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients before surgical resection.

Retrieval analysis of PEEK rods pedicle screw system: three cases analysis.

PURPOSE: To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties. METHOD: Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct. RESULTS: All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure. CONCLUSION: PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.

Evaluation of response to neoadjuvant chemotherapy in osteosarcoma using dynamic contrast-enhanced MRI: development and external validation of a model.

OBJECTIVE: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. METHODS: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). RESULTS: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. CONCLUSION: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.

The histopathological changes of liver and testis of Japanese quail chicks fed different levels of dietary L-valine.

This experiment was carried out to investigate the histological changes of liver and testis of Japanese quail fed different levels of dietary valine (Val) in low protein diet. A total of 1000 one-day-old Japanese quail chicks (mixed sex) were assigned to five experimental diets including diets containing 7.5, 8.5, 9.5, 10.5 and 11.5 g digestible (dig.) Val/kg diet in a completely randomized design, with 5 replicates of 40 quail chicks per pen. Experimental diets were formulated to be isoenergetic and isonitrogenous (170 g crude protein/kg) to meet nutrients recommendation of growing quails suggested by Brazilian tables. At d 42, quail chicks were slaughtered, and tissue samples were collected and fixed to evaluate the histological indices of liver and testis. High levels of Val, increased (P < 0.05) diameter of liver cell nucleus and liver hepatocytes in both male and female. While 11.5 g Val showed mild hepatosteatosis, bile duct hyperplasia was observed in 10.5 g Val. In 7.5 and 8.5 g Val groups, there was no negative effects on the liver histology. The male quail chicks which fed on diets containing 8.5 g Val had better significant (P < 0.05) reproductive indexes [Tubular differentiation (TDI) and spermatic index (SI)]. In conclusion, the use of high levels of Val (≥ 9.5 g dig. Val/kg diet) during d 0 - 42 of age can lead to histological damage in liver and testis of quail chicks.

Histological tumor response predicts clinical outcome in patients with colorectal peritoneal metastasis treated with preoperative chemotherapy followed by cytoreduction and HIPEC.

Objectives: Up to one quarter of the patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PM). The aims of this retrospective study were to characterize the histological response of the PM of CRC to preoperative chemotherapy and evaluate the potential prognostic value, in terms of survival. Methods: This retrospective unicentric study evaluated a group of 30 patients treated between 2010 and 2020 at the São João University Hospital Center with preoperative chemotherapy, followed by cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy. The evaluation of the histological response was done using two scores: the tumor regression grading (TRG) and the peritoneal regression grading score (PRGS). Results: Mean post-procedure survival is higher in the PRGS 1-2 group (74.19 months) vs. the PRGS 3-4 group (25.27 months) (p=0.045), as well as in the TRG 1-2 group (74.58 months) vs. TRG 4-5 (25.27 months) (p=0.032). As for progression-free survival (PFS), the PRGS 1-2 group had a mean value of 58.03 months vs. PRGS 3-4 which had 11.67 months (p=0.002). Similar was observed with the TRG 1-2 group, which had a mean PFS of 61.68 months vs. TRG 4-5 with 11.67 months (p=0.003). Conclusions: A better histological response to preoperative chemotherapy, represented as a lower PRGS and TRG value, is associated with longer post-procedure survival and progression-free survival in this group of patients. That is, these two scores have prognostic value.

Gastric cancer: histological response of tumor and metastatic lymph nodes for perioperative chemotherapy.

BACKGROUND: Gastric cancer is the fourth cancer most common in the world and the second cause of cancer-related deaths. Perioperative chemotherapy may reduce tumor burden and decrease lymph node invasion, improving R0 resections rates. On the other hand, administered before surgery, chemotherapy may cause fibrosis and tissue edema, with potential increase of surgical difficulty and in the number of post-operative complications. Therefore, we aim to investigate the effect of perioperative chemotherapy for tumor burden and metastatic lymph nodes of gastric cancer. METHODS: Retrospective analysis of all patients submitted to perioperative chemotherapy and surgery, between January 2010 and June 2020, which showed lymph node regression and tumor regression (Becker's classification). RESULTS: A total of 112 patients with an average age of 61.9 years were analyzed. About 90.2% completed three cycles of perioperative chemotherapy. Good tumor response to chemotherapy (<10% residual tumor) was achieved in 21.3% of patients. Only three patients obtained a complete pathological response. A median lymph node response of 33.3% was achieved in our series. CONCLUSION: Despite no evident outstanding regression rate was observed, perioperative chemotherapy seems to be useful in obtaining a R0 resection in gastric cancer, even in advanced gastric cancer.

INTRODUCCIÓN: El cáncer de estómago es el cuarto tipo de cáncer más común y la segunda causa de muerte relacionada con el cáncer. La quimioterapia perioperatoria puede reducir la carga tumoral y disminuir la invasión de los ganglios linfáticos. Por otro lado, administrada antes de la cirugía, la quimioterapia puede causar fibrosis y edema tisular, aumentando potencialmente la dificultad quirúrgica y el número de complicaciones posoperatorias. Nuestro objetivo es investigar el efecto de la quimioterapia perioperatoria sobre la carga tumoral y los ganglios metastásicos en el cáncer gástrico. MÉTODOS: Análisis retrospectivo de todos los pacientes sometidos a quimioterapia y cirugía, entre enero de 2010 y junio de 2020. RESULTADOS: Se analizaron 112 pacientes con una edad media de 61.9 años. El 90.2% completó 3 ciclos de quimioterapia perioperatoria. Se logró una buena respuesta tumoral a la quimioterapia (< 10% de tumor residual) en el 21.3% de los pacientes. Tres pacientes lograron una respuesta patológica completa. En nuestra serie se logró una mediana de respuesta de los ganglios linfáticos del 33.3%. CONCLUSIÓN: Aunque no se observó una tasa de regresión manifiesta, la quimioterapia perioperatoria parece ser útil para lograr una resección R0 en el cáncer gástrico, incluso en el cáncer gástrico avanzado.

MRI for evaluation of preoperative chemotherapy in osteosarcoma.

INTRODUCTION: Our study aims to highlight the role of Magnetic Resonance Imaging (MRI) in monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of the long bones. METHODS: In this retrospective study, data from the Orthopaedics and Internal Medicine Department of Istanbul University Cerrahpasa Hospital was used. We selected the study cohort from our departmental database of patients with biopsy-proven osteosarcoma initially treated with preoperative chemotherapy at Istanbul University Cerrahpasa Hospital from 2010 to 2017. MRI images of 21 patients (male/female ratio: 2.5 with a mean age of 22) were analysed before and after neoadjuvant chemotherapy. The histological response to chemotherapy was graded according to The Huvos classification. Computed volumetry was performed to determine the size of the intramedullary component, largest enhancing component, and tumour volume. P < 0.05 was considered to denote a significant difference. RESULTS: The mean tumour volume before chemotherapy was 409 cm3. After chemotherapy, however, the tumor volume increased to 701 cm3 (p = 0.10). The mean intramedullary component size of the tumours before chemotherapy was 10.5 cm3 while after chemotherapy was 11.2 cm3 (p = 0.06). The mean largest enhancing component size was 3.09 cm3 and after chemotherapy, decreased to 2.34 cm3 (p = 0.01). Neoadjuvant chemotherapy significantly changed the tumour composition. Tumour volume and intramedullary component size measurements failed to demonstrate a significant correlation and could not be used as a prognostic factor for tumour response to preoperative chemotherapy. We suggest that the largest enhancing component of a tumour can be a potential prognostic marker for assessing the tumour response. CONCLUSION: MRI can help predict histological necrosis after the administration of preoperative chemotherapy to osteosarcoma via measuring the largest enhancing component. Hence, it is a promising preoperative indicator of response to neoadjuvant chemotherapy. However, tumour volume and intramedullary component size measurement are not effective predictors of histological necrosis. The increased volume and intramedullary component of the tumour were attributed to the increased central necrotic component of the tumour after chemotherapy. IMPLICATIONS FOR PRACTICE: In this study, we showed that MRI can help predict histological necrosis and thus, prognosis after the administration of preoperative chemotherapy to osteosarcoma via the measurement of the largest enhancing component of the tumour. This is significant because histological necrosis is currently the gold standard method for assessing the treatment response. However, this requires an invasive procedure, and a non-invasive method would be beneficial. Assessing the treatment response through imaging after the completion of the initial chemotherapy will also help determine the final surgical approach and thus predict survival.

Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas.

BACKGROUND: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. METHODS: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. RESULTS: A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893-18.188, p = 0.070). CONCLUSION: The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases.

BACKGROUND: The red blood cell distribution width (RDW) level is a potential prognostic factor for solid tumours. We aimed to investigate the predictive value of pre-neoadjuvant chemotherapy (pre-NAC) RDW, preoperative RDW and the change in RDW on the pathological response and prognosis of patients with colorectal liver metastasis (CRLM), which was helpful for treatment decision-making, surveillance and prognostication. METHODS: This retrospective study analyzed clinicopathologic data, treatments and outcomes of 150 CRLM patients treated with NAC followed by liver resection at our hospital. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcome was postoperative major complications. The RDW level was presented as the RDW-SD level and the RDW-CV level. The optimal cut-off of RDW level was determined by X-tile analysis. The change in RDW was scored as 0 (decreased pre-NAC RDW and decreased preoperative RDW), 2 (elevated pre-NAC RDW and elevated preoperative RDW), or 1 (all other combinations). Multivariable logistic regression analysis was performed to determine the relationships between the tumour characteristics and pathological response and the postoperative major complications. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with survival. RESULTS: The optimal cut-off values of the RDW-CV and RDW-SD levels for survival were 13.5% and 42.2 fl, respectively. The multivariate analysis showed that a preoperative RDW-CV ≥13.5% (OR =3.215, 95% CI: 1.299-7.958, P=0.012) significantly predicted a favorable pathological response. The multivariate analysis revealed that a pre-NAC RDW-CV ≥13.5% (OR =2.462, 95% CI: 1.080-5.615, P=0.032) significantly predicted postoperative major complications. In the multivariate analysis, an RDW-CV change =2 (HR =0.487, 95% CI: 0.309-0.768, P=0.002) was a significant predictor of better PFS. The multivariate analysis also revealed that an RDW-SD change =2 (HR =0.532, 95% CI: 0.332-0.854, P=0.009) were an independent predictor of better OS. CONCLUSIONS: This study revealed that pre-NAC RDW, preoperative RDW and RDW changes may be reliable markers that could predict a pathological response and prognosis in CRLM patients receiving NAC followed by liver resection.

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined. OBJECTIVE: To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC. METHODS: The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis. RESULTS: Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR. CONCLUSIONS: pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.

Does MTA provide a more favourable histological response than other materials in the repair of furcal perforations? A systematic review.

BACKGROUND: There is no consensus on which furcal perforation repair material induces a more favourable histological response. This systematic review of laboratory studies provides an overview of the studies comparing repair materials in animal models. OBJECTIVES: To evaluate whether mineral trioxide aggregate (MTA) yields a more favourable histological response than other materials when used to repair furcal perforations in animal experimental models. METHODS: This review followed the PRISMA checklist. The studies included various materials used to repair furcal perforations and compared the histological responses with MTA. An electronic search was conducted in EMBASE, PubMed, Scopus and Web of Science up to 2 September 2020, with no language or publication date restrictions. Studies whose full text was unavailable were excluded. The ARRIVE and SYRCLE tools were used to assess the methodological quality and risk of bias (RoB) of the studies. RESULTS: The studies included in the qualitative synthesis were conducted in rat (n = 3) and dog (n = 17) models. They were classified as having a low quality, high methodological heterogeneity and high RoB. MTA and Biodentine, the materials most often compared, reduced the inflammatory reaction to mild over time. In addition, a mineralized tissue was formed in all studies. The response yielded by MTA was better than or equivalent to that of the other tested materials. DISCUSSION: This review confirmed that MTA is the reference standard material for furcal perforation repair. However, research using animal models has inherent limitations, and the substantial methodological heterogeneity across the studies included should be considered. Therefore, the knowledge generated by this systematic review should be translated into clinical practice cautiously. CONCLUSIONS: Features described in the report and quality assessment guidelines, such as PRIASE, ARRIVE and SYRCLE, should guide researchers. Despite the high RoB and the low methodological quality of the studies included, findings indicated that MTA yields a more favourable histological response than other materials in the repair of furcal perforations. REGISTRATION: PROSPERO (CRD42020181297).

Adjuvant and neoadjuvant chemotherapy for osteosarcoma: JCOG Bone and Soft Tissue Tumor Study Group.

The usefulness of adjuvant chemotherapy for high-grade osteosarcoma was established by two randomized, controlled trials conducted in the 1980s, which used six drugs, doxorubicin, cisplatin, high-dose methotrexate, bleomycin, cyclophosphamide and actinomycin D. Since then, development has been promoted in the direction of introducing preoperative chemotherapy, changing post-operative adjuvant chemotherapy according to histological effects, adding ifosfamide as a key drug and strengthening adjuvant chemotherapy. No clinical trials, however, have shown the effectiveness of study treatment, and the improvement of treatment results during that time has been slight, although the JCOG0905 study is now going to verify the effectiveness of introducing ifosfamide for patients who experienced limited preoperative therapeutic effects. We are desperately looking for a breakthrough.

10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis.

PURPOSE: The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. METHODS: In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. RESULTS: 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). CONCLUSIONS: The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

Histological response to neoadjuvant chemotherapy in localized Ewing sarcoma of the bone: A retrospective analysis of available scoring tools.

AIM: The aim is to evaluate which of the existing scoring systems of histological response to neoadjuvant chemotherapy best stratifies the clinical outcome of patients with localized Ewing sarcoma of bone. METHODS: 474 patients with diagnosis of localized Ewing sarcoma of bone were included. The median follow-up was 13.5 years. RESULTS: The overall survival and the disease-free survival (DFS) were 70.8% and 63.9% at 5 years. The percentage of histological response to neoadjuvant chemotherapy ranged between 5% and 100% (mean 83%). The agreement between Bologna System and the different percentual cut-offs of histological response to neoadjuvant chemotherapy was high, with kappa statistics of 0.83 for a cut-off of ≥90%; 0.86 for a cut-off of ≥95%; 0.79 for a cut-off of ≥96% and 0.61 for a cut-off of 100%. Statistically higher DFS rates for good responders compared to poor responders were found when using each given system. Model performance indicators showed that Bologna system had a lower AIC score and a higher c-statistics to predict DFS. When the patients classified as good responders using the different percentual cut-offs of histological response to neoadjuvant chemotherapy, were instead re-classified using the Bologna system, statistical differences were noted in DFS within each specific group. CONCLUSIONS: All scoring tools to evaluate histological response to neoadjuvant chemotherapy offer good predictive value for DFS in localized Ewing's sarcoma of bone. The Bologna system better stratifies those patients with histological response to neoadjuvant chemotherapy between 90 and 99%, representing a more reliable scoring tool in this subset.

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer.

PURPOSE: A proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates. PATIENTS AND METHODS: Patients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes. RESULTS: Records were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P=0.047), a limited parietal invasion (P=0.001), clinically negative lymph node (P<0.001) and a circumferential extent greater than 50% (P=0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6cm were associated with no response to treatment (P=0.049 and P=0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P<0.001 and P=0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P=0.001). CONCLUSION: The identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.

Impact of preoperative chemotherapy on the histological response of patients with peritoneal metastases from colorectal cancer according to peritoneal regression grading score (PRGS) and TRG.

BACKGROUND: This study evaluated the histologic response after preoperative systemic therapy (pST) using the Peritoneal Regression Grading Score (PRGS) and tumor regression grade (TRG) classifications for patients with peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty-three patients were selected from a prospective database of 196 patients who underwent CRS followed by HIPEC for synchronous PM from CRC. In all study patients, biopsies of the PM obtained before pST (during the first laparoscopy) and after pST (during cytoreductive surgery) were compared. RESULTS: Complete (PRGS 1), Major (PRGS 2), Minor (PRGS 3) and no histological responses (PRGS 4) were obtained in 17,5%, 52% and 13% and 17,5% of patients, respectively. Major (TRG 1-2), partial (TRG3), and no (TRG4-5) histological tumor regression were observed in 61%, 9% and 30% of patients, respectively. Regardless of the classification applied, median OS was significantly higher in patients with a "complete or major" response than in those with a "minor/partial or no" response (54 vs. 26 months, p < 0.05). CONCLUSIONS: The PRGS and TRG can be used in clinical practice to evaluate the histological response after pST. This study demonstrated that a complete histologic response of PM from CRC can be obtained after pST.

Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: A mouse model study.

This experimental study evaluated the histological response of peritoneal metastases (PM) from colorectal cancer (CRC) after preoperative systemic chemotherapy (pCT). The results demonstrated that the Peritoneal Regression Grade Score could be used in medical practice. AIM: The aim was to evaluate the histological criteria used by the tumour regression grade (TRG) and Peritoneal Regression Grade Score (PRGS) for determining the response to chemotherapy (CT), in a mouse model of peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty immunocompetent BALB/c mice were randomized into four groups at day (D) 10 after intraperitoneal (ip) injection with bioluminescent CRC tumour cells (CT26-luc). A histology before treatment group was obtained by sacrifice on D10; the other groups all received one of the following ip treatments over 15 days: 5% glucose (control, G5); 5-fluorouracil (5FU, 0.03 mg/g); or 5FU with oxaliplatin (Ox, 0.006 mg/g). The histological response (HR) was analysed by comparing the histology of PM before and after treatment, using both scores: TRG and PRGS. RESULTS: All mice showed limited PM as visualised by bioluminescence and confirmed at the time of sacrifice in the histology before treatment group. The mean peritoneal carcinomatosis index (PCI) was = 8 [6-10], The rate of complete HR was significantly higher in the Ox-5FU group (83.3%) than 5FU group (0%) and G5 group (0%) (p = 0.016). Fibrosis was present only in CT-treated groups (p = 0.05). PCI, ascites volume and haemorrhagic ascites were significantly higher in the G5 group than CT groups (p < 0.05). CONCLUSIONS: The TRG score can be used in practice when we want to compare the HR between the primary tumour and the PMs. The PRGS is a good measure of HR and is correlated with the efficacy of CT.

Neo-adjuvant Chemotherapy-Induced Neutropenia Is Associated with Histological Responses and Outcomes after the Resection of Colorectal Liver Metastases.

BACKGROUND: Neutropenia, the major adverse event in chemotherapy, is associated with favourable clinical outcome in several solid tumours. We aimed to investigate the predictive value of neo-adjuvant chemotherapy (NAC)-induced neutropenia for the pathological response and prognosis in colorectal liver metastases (CRLM) patients. METHODS: A retrospective review was performed in 141 CRLM patients receiving NAC followed by liver resection. A logistic regression was applied to analyse potential predictors. A Cox proportional hazards analysis was used to analyse survival. RESULTS: Neutropenia due to NAC was observed in 42.6% (60/141) of all patients, and grade 3/4 neutropenia was noted in 31.7% (19/60). A pathological response (tumour regression grade (TRG) 1-3) was reported in 46.1% (65/141) of patients. Multivariate analysis showed that neutropenia significantly predicted the favourable pathological response (OR = 3.718, 95% CI 1.716-8.329, P = 0.001), as well as targeted therapy, good differentiation and preoperative CEA < 10 ng/ml as independent predictors of favourable histological response. Of the patients, 54.6% (77/141) had postoperative complications, including 28 major complications (28/77, 36.4%). Severe neutropenia significantly predicted postoperative major complications in multivariate analysis (OR = 4.077, 95% CI 1.184-14.038, P = 0.026). Compared to patients without neutropenia, patients with neutropenia had significantly better progression-free survival (PFS) (P = 0.007; mPFS, 10.2 months vs. 6.7 months). Patients with histological response had significantly better PFS than patients with no histological response (P = 0.001; mPFS, 10.0 months vs. 5.5 months). According to multivariate analyses, neutropenia was a significant predictor for better PFS (HR = 0.613, 95% CI 0.406-0.925, P = 0.020) but not OS. CONCLUSIONS: For CRLM patients receiving NAC followed by liver resection, NAC-induced neutropenia was a significant predictor of favourable pathological response, postoperative major complications and better prognosis, which makes it useful for CRLM patients in guiding treatment approaches and prognosis assessments.

Differences in intraosseous and extraosseous post-chemotherapy regression of Ewing sarcomas and their influence on prognosis.

BACKGROUND: In Ewing sarcomas (ES), histological response to polychemotherapy is the main prognostic factor. We aimed at evaluating the histological response separately for the extraosseous and intraosseous tumor compartment as well as its prognostic influence. METHODS: Thirty-one patients with ES and marked soft tissue expansion, treated at our department between January 2006 and December 2015, were retrospectively included. Data was taken from medical records. Original histologic specimens of the resected tumors were re-evaluated separately for intra- and extraosseous tumor regression according to Salzer-Kuntschik regression grading. Multivariate survival analysis with stepwise backward variable selection was calculated to determine the impact of extraosseous and intraosseous regression on prognosis. RESULTS: All patients had received chemotherapy, 15 (48.4%) had been administered preoperative radiotherapy. Extraosseous tumor regression was significantly worse than intraosseous regression (Wilcoxon signed-rank test, p = 0.018). While neither intraosseous nor extraosseous tumor regression had an impact on overall survival, extraosseous complete remission had a beneficial impact on event-free-survival in the multivariate analysis (Cox-regression; hazard ratio: 0.148, 95% confidence interval 0.031-0.707, p = 0.017). CONCLUSIONS: On average, regression of ES seems to be worse in the extraosseous tumor compartment following preoperative chemotherapy. Moreover, extraosseous tumor regression may have a stronger prognostic influence on event-free survival than intraosseous regression.