Next generation antibacterial strategies for regenerative endodontic procedures: A scoping review.

BACKGROUND: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2). OBJECTIVES: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives. METHODS: Four databases (PUBMed, Cochrane, ClinicalTrials and Science Direct) were searched until 1st May 2023. RESULTS: A total of 918 records were identified, 133 were screened and assessed for eligibility, and 87 articles were included. The findings show that (1) clinical studies are only available for CAS, (2) although next generation strategies are the most studied approach since 2017, they are all at the pre-clinical stage, (3) most of the next generation strategies use galenic forms which offer cell support and colonization and which simultaneously contain antibacterial molecules as alternatives to CAS and to antibiotics in general, (4) standardization is required for future research, specifically regarding the bacterial strains studied, the use of biofilm studies and the cellular behaviour assessments. CONCLUSION: Although NGAS are promising strategies to improve REPs in the context of infection, the current evidence is mostly limited to pre-clinical studies. Further methodological improvement is required to allow relevant comparisons between studies and to reduce the time from bench to bedside.

Transarterial chemoembolization (TACE) for neuroendocrine liver metastasis (NELM): Predictive value of volumetric arterial enhancement (VAE) on baseline MRI.

BACKGROUND: Neuroendocrine tumors (NETs) belong to a rare family of tumors whose incidence has increased significantly over the past 50 years. PURPOSE: To evaluate the prognostic value of volumetric arterial enhancement (VAE) on baseline magnetic resonance imaging (MRI) for patients with neuroendocrine liver metastasis (NELM) treated using transarterial chemoembolization (TACE). MATERIAL AND METHODS: Between October 2012 and December 2018, VAE in 37 patients was measured with a semi-automatic volume of Interest (VOI) on subtracted T1 sequence in the arterial phase. Patients underwent 1-3 sectoral lipiodol TACE. Radiologic response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) at the treatment cycle end and progression free survival were determined. RESULTS: Median age was 68.0 (60.0; 73.0). Twenty-three patients (62%) had a partial response, 10 (27%) had stable disease, four (11%) had progressive disease. VAE was a significant (P<0.05) predictor of radiologic response. Median progression free survival was 13 months (IC 95: 8; 16). In univariate analysis, significant predictors of local progression were alkaline phosphatase (AP) (P=0.035), Ki-67 index (P=0.014), and VAE (P<0.01). VAE over 500ms and Ki-67 index over 3%were risk factors of progression (P=<0.01) in multivariate analysis. CONCLUSION: VAE before TACE could be predictive of radiologic response and could be related to oncologic outcomes in patients with NELM.

Hyperprogressive Disease in Anorectal Melanoma Treated by PD-1 Inhibitors.

The 5-year survival rate of primary anorectal malignant melanoma is less than 20%. Optimal treatment of this condition remains controversial regarding locally disease, and whether any preferential survival benefit arises from either abdominoperineal resection or wide local excision remains unknown. The majority of patients progress to metastatic disease, and for decades, the use of chemotherapies, such as platines or dacarbazine, has been advocated to improve overall survival. The therapeutic use of new checkpoint inhibitors in a variety of trials has provided evidence for an antitumoral effect of PD-1 and/or CTL4 inhibitors in mucosal melanomas, but these treatments must still be further evaluated. Some anecdotal occurrences of rapid progression [i.e., hyperprogressive disease (HPD)] while using these immune agents have been described, suggesting potentially deleterious effects of these drugs for some patients. We report a 77-year-old male metastatic anorectal melanoma patient presenting with HPD over 2 months of a PD1 inhibitor treatment course and document this HPD blood phenotype.

Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer.

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects. The favorable toxicity profile of the combination of 5-fluorouracil with oxaliplatin, together with its significant antitumor activity in several gastrointestinal malignancies, led to the evaluation of its efficacy and tolerability in patients with advanced grade 1/2 (G1/G2) NETs. The endpoints of the study were tumor response (according to the Response Evaluation Criteria in Solid Tumors 1.1), overall survival (OS), progression-free survival (PFS) and symptom improvement. From January, 2013 to January, 2015, during our Regional Multidisciplinary Tumor Board dedicated to NETs (RENATEN network), FOLFOX was recommended for the treatment of metastatic NETs as first-line therapy or after failure of other therapies. The inclusion criteria were metastatic, well-differentiated G1/G2 NETs, progressing within the last 3 months. Cases with previous antitumor therapy were allowed. The patients received modified FOLFOX-6 and were assessed every 3 months by computed tomography or magnetic resonance imaging examinations. A total of 31 patients were included. The median follow-up was 20 months [95% confidence interval (CI): 15-27]. Nine patients (29%) exhibited a partial response, and 13 (41%) achieved stable disease; the disease control rate was 70%. A total of 9 patients exhibited disease progression. The control rate was 78% for pancreatic and 65% for extrapancreatic NETs. The median OS was not reached; the 1- and 2-year OS rates were 89 and 70%, respectively (Fig. 1). No significant difference in OS was observed between the <5 and 5-20% Ki-67 subgroups (P=0.41) (Fig. 2A) or according to primary tumor location (P=0.71) (Fig. 2B). The median PFS was 14.1 months (95% CI: 9.3-24.1), with no significant difference in PFS between the Ki-67 subgroups (P=0.26) (Fig. 3A) or by primary tumor location (P=0.995) (Fig. 3B). The median time to treatment failure was 14.72 months (95% CI: 10.0-not estimable). No unusual toxicity or toxicity-related deaths were reported. Finally, 7 of 9 patients who achieved a partial response benefited from a break in treatment of ≥3 months. The median duration of this break was 9.2 months (range, 3-42 months). Of the 13 patients with stable disease, 12 may have also benefited from a chemotherapy break. The median break duration was 10 months (range, 0.5-26 months).

Treatment of Pancreatic Adenocarcinoma in Elderly Patients over 75 Years of Age: A Retrospective Series of 129 Patients.

PURPOSE: To better know the presentation and outcome of pancreatic adenocarcinoma in patients above 75 years of age. METHOD: Retrospective analysis of consecutive patients with a pancreatic adenocarcinoma seen in the Comprehensive Cancer Center of Marseille between January 2002 and January 2012 was used. RESULTS: During these 10 years, 129 patients older than 75 years of age were seen, 61 females and 68 males, median age 78. At diagnosis, the tumor was metastatic in 45%. First line treatments were: surgical resection in 22 cases, radio-chemotherapy in 20 cases (1 operated on later), systemic chemotherapy in 59 cases, and best supportive care alone in 28 cases. Resection was possible in 19 cases and was R0 in 17; post-operative mortality was 0%, and half received adjuvant chemotherapy. Median overall survival was 43 months with a 2-year overall survival of 64%. For locally advanced tumor, 16 received best supportive care and 33 a specific treatment (20 cases of radio-chemotherapy). Median overall survival was 9.1 months and 2-year overall, survival was 6.1%. Among the 58 metastatic patients, 79% received systemic chemotherapy (most by gemcitabine); tolerance was correct in half. Median overall survival was 4.7 months, with a 2-year overall survival of 5.3%. CONCLUSIONS: Surgery of pancreatic adenocarcinoma is feasible and safe in elderly patients with good outcomes. In advanced and metastatic patients, the outcome is poor despite a correct tolerance of systemic chemotherapy. Randomized trials specially designed for this population are urgently needed.

High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature.

Desmoid tumors are rare benign monoclonal fibroblastic tumors. Their aggressiveness is local with no potential for metastasis or dedifferentiation. Here we report on a 61-year-old patient who presented a locally advanced breast desmoid tumor diagnosed 20 years after post-operative radiotherapy for breast carcinoma. After 2 years of medical treatment, a high-grade undifferentiated pleomorphic soft tissue sarcoma arose within the desmoid tumor. Despite extensive surgery removing both tumors, the patient showed locoregional relapse by the sarcoma, followed by multimetastatic progression, then death 25 months after the surgery. The arising of a soft tissue sarcoma in a desmoid tumor is an exceptional event since our case is the fourth one reported so far in literature. It reinforces the need for timely and accurate diagnosis when a new mass develops in the region of a preexisting desmoid tumor, and more generally when a desmoid tumor modifies its clinical or radiological aspect.

Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.