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The article discusses the use of Total Neoadjuvant Therapy (TNT) for the treatment of locally advanced rectal cancer. The article highlights the benefits of TNT, including improved disease-free survival and increased complete response rates. However, there is a lack of consensus on the definition of a "near" complete response (nCR), which complicates discussions with patients. The article also addresses the timing of assessment for complete response and the potential risks of delaying surgery. The authors emphasize the need for further research and data to improve patient outcomes and decision-making in rectal cancer treatment. [Extracted from the article]

Background: Pelvic exenteration surgery is complex, necessitating co‐ordinated multidisciplinary input and improved referral pathways. A state‐wide pelvic exenteration multidisciplinary team (MDT) meeting was established in SA and the outcomes of this were audited and compared with historical data. Methods: All patients referred for discussion between August 2021 and July 2022 to the SA State‐wide Pelvic Exenteration MDT were included in this study. MDT discussion centred around disease resectability, risk versus benefit of surgery, and need for local or interstate referral. Prospective data collection included patient demographics and MDT recommendations of surgery, palliation, or referral. Patients referred for surgery locally or interstate were compared with a retrospective patient cohort treated previously between January and December 2020. Results: Over 12 months, 91 patients were discussed (including nine multiple times), by a mean of 18 meeting participants each month. Forty‐eight patients (58.5%) had primary malignancy, 25 (30.5%) recurrent malignancy, and 9 (11.0%) had non‐malignant disease. Colorectal cancer was the most common presentation (56.1%), followed by gynaecological (30.5%) and urological (6.1%) malignancy. Pelvic exenteration surgery was recommended to be performed locally in 53.7% of patients and the remainder for non‐surgical treatment, palliation, or re‐discussion. During this time, 44 patients underwent surgery locally (versus 34 in 2020) and only 4 referred interstate (versus 8 in 2020). Conclusion: The establishment of a dedicated state‐wide pelvic exenteration MDT has resulted in better coordination of care for patients with locally advanced pelvic malignancy in SA, and significantly reduced the need for interstate referral. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare current treatment response rates with personalized Total Neoadjuvant Therapy (pTNT), against extended chemotherapy in the 'wait period' (xCRT) and standard chemoradiotherapy (sCRT) with adjuvant chemotherapy for rectal cancer. Methods: This was a multicentre retrospective cohort analysis. Consecutive patients with rectal cancer treated with pTNT over a 3.9‐year period were compared to a historical cohort of patients treated with xCRT or sCRT as part of the published WAIT Trial. pTNT patients received 8 cycles mFOLFOX6 or 6 cycles CAPOX in the neoadjuvant setting (no adjuvant treatment). Patients in the WAIT Trial received either 3 cycles 5‐FU/LV during the 10‐week wait period after chemoradiotherapy or standard chemoradiotherapy, followed by adjuvant chemotherapy. The primary endpoint was overall complete response (oCR) rate defined as the proportion of patients who achieved either complete clinical response (cCR) or pathological complete response (pCR). Results: Of 284 patients diagnosed with rectal cancer during the 3.9‐year period, 107 received pTNT. Forty of these were matched with 49 patients from the WAIT Trial (25 received xCRT and 24 received sCRT). There was a significant difference in oCR between the groups (pTNT n = 21, xCRT n = 6, sCRT n = 7, P = 0.043). Of the patients that underwent surgery, pCR occurred in 13 patients with no significant difference between groups (P = 0.415). There were no significant differences in 2‐year disease‐free survival or overall survival. Conclusion: Compared with sCRT and xCRT, pTNT results in a significantly higher complete response rate which may facilitate organ preservation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. Methods: A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. Results: Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. Conclusion: Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to compare the in vitro cytokine response of gingival fibroblasts (GF’s) from healthy and inflamed human gingival tissues and to assess whether GF’s from inflamed gingivae are capable of mounting a secondary inflammatory response after exposure to P. gingivalis LPS.Materials and methods: GF’s were obtained from healthy donors and periodontitis patients and cultured in vitro. Cells were exposed to P. gingivalis LPS for 24h before measurement of MCP-1, GRO, IL-6, IL-8 and VEGF using a bead-based multiplex assay. Statistical comparisons were made between LPS-exposed GF’s and unstimulated cells as well as the two patient groups by two-way ANOVA.Results: GF’s exposed to P. gingivalis LPS significantly increased their production of MCP-1, GRO, IL-6, IL-8 and VEGF compared to unstimulated cells. GF’s isolated from inflamed tissue from periodontitis patients demonstrated consistently less cytokine production after exposure to P. gingivalis LPS, most notably for GRO and IL-6.Conclusions: The current study demonstrates that GF’s play an active role in the inflammatory response in periodontal disease by producing a number of chemokines and cytokines. Furthermore, inflamed GF’s may be compromised in their ability to mount an adequate secondary immune response in relation to chemokine/cytokine production.Clinical relevance: The compromised inflammatory cytokine response of inflamed human gingival fibroblasts to P. gingivalis LPS may impact on their ability to recruit and activate inflammatory cells while maintaining persistent inflammation, a key feature of periodontal disease. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study investigated the role of Lactobacillus rhamnosus GG (LGG) on bone loss and local and systemic inflammation in an in vivo mouse model of experimental periodontitis (PD). Materials and Methods: Experimental PD was induced in mice by oral inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum over a period of 44 days. The probiotic LGG was administered via oral inoculation or oral gavage prior to, and during disease induction. The antimicrobial activity of LGG on the inoculum was also tested. Alveolar bone levels and gingival tissue changes were assessed using in vivo microcomputed tomography and histological analysis. Serum levels of mouse homologues for IL‐8 were measured using multiplex assays. Results: Pre‐treatment with probiotics either via oral gavage or via oral inoculation significantly reduced bone loss (p < .0001) and gingival inflammation (p < .0001) when compared with PD group. Oral gavage treatment group had significantly less tartrate‐resistant acid phosphatase positive cells (p < .02) then PD group. LGG showed no antimicrobial activity against P. gingivalis and F. nucleatum. Conclusions: Lactobacillus rhamnosus GG effectively suppresses bone loss in a mouse model of induced PD irrespective of the mode of administration. [ABSTRACT FROM AUTHOR]

Aim: To compare the levels of the soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG) and their relative ratio in gingival crevicular fluid (GCF) among periodontitis patients with varying smoking histories., Material and Methods: GCF samples were collected from 149 periodontitis patients who were never smokers (n=58), former smokers (n=39) and current smokers (n=52). sRANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays., Results: sRANKL, OPG and their relative ratio were not statistically significant among the never smokers, former smokers and current smokers. However, OPG was significantly reduced and subsequently the sRANKL:OPG ratio was significantly increased in the high pack-years group as compared with never smokers. The positive correlation between pack-years and the sRANKL:OPG ratio remained statistically significant after adjusting for age and current smoking status., Conclusion: Increased lifetime exposure to cigarette smoking above a minimum threshold suppresses OPG production and leads to increased sRANKL:OPG. This may partially explain increased bone loss in smoking-related periodontitis.