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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]

Background: Several studies have highlighted poor compliance with surveillance colonoscopy guidelines. The National Health and Medical Research Council (NHMRC) guidelines were revised in 2018 and were more complex than the previous iteration (2011). The aim of this study was to determine the impact of 2018 NHMRC polyp surveillance guidelines on compliance with colonoscopy surveillance intervals. Methods: A multicentre retrospective clinical audit was conducted between January 2020 and February 2021. Patients awaiting a colonoscopy for polyp surveillance at two public tertiary care hospitals in South Australia were included. Compliance rates of recommended polyp surveillance colonoscopy intervals after implementation of 2018 NHMRC guidelines were compared with 2011 NHMRC guidelines. The projected impact on colonoscopy bookings of the change in guideline intervals was modelled to 5 and 10 years, factoring in differences in compliance. Results: Of 3996 patients awaiting colonoscopy services at two public hospitals in South Australia, 1984 patients (60% male, median age 61 years) were waitlisted for polyp surveillance. Overall compliance with surveillance guidelines was >60%. Implementation of the 2018 NHMRC guidelines significantly reduced compliance from 65.8% (2011 guidelines) to 50.8% (2018) (χ2 <0.001, OR 0.5). Modelling projections to 5 and 10 years demonstrated that application of the 2018 guidelines significantly increases the projected number of colonoscopy bookings per year. Conclusion: The revised 2018 NHMRC guidelines have resulted in significantly poorer compliance post‐implementation, possibly due to their increased complexity. This has potential to increase the surveillance colonoscopy waiting list burden. [ABSTRACT FROM AUTHOR]

Background: The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery. Methods: The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one‐off snapshot measure. Univariate and multivariable logistic regression analyses were performed. Results: Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety‐three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk‐factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side‐to‐side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02). Conclusion: This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI. [ABSTRACT FROM AUTHOR]

This study investigated the efficacy of Er,Cr:YSGG laser and ultrasonic activated irrigation on eradicating a mixed‐species biofilm grown in root canals with complex anatomy. The biofilm was grown over 4‐weeks in the root canals of decoronated human mandibular molar teeth. Control roots received no further treatment. The remaining roots were chemomechanically prepared using different irrigating protocols: 4% NaOCl and 15% EDTAC with ultrasonic activated irrigation and laser activated irrigation using power settings of 0.5 W and 0.75 W. Cellular viability was determined using serial plating. One tooth from each group was subjected to qualitative SEM analysis. Quantification by culturing revealed significant differences between control group and all other treatment groups. This study demonstrated that chemomechanical irrigation with laser and ultrasonic activated irrigation significantly reduced the bacterial load from complex root canal systems; however, there were no significant differences found between the experimental groups. [ABSTRACT FROM AUTHOR]

MOVIMIENTO DE MUJERES EN CENTROAMERICA. By Ana Leticia Aguilar, Blanca Estela Dole, Morena Herrera, Sof[acute{i}]a Montenegro, Lorena Camacho, and Lorena Flores. (Managua: Programa Regional La Corriente, 1997. Pp. 511.) GENDER [...]

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]

Objectives: To investigate if there is subspecies specific migration to the placenta by Fusobacterium nucleatum (Fn) and to determine whether experimentally induced periodontitis results in adverse pregnancy outcomes (APO) in mice. Methods: Periodontitis was induced in pregnant mice using an inoculum of Fn and Porphyromonas gingivalis. In parallel, four sub-species of Fn were individually injected into the circulatory system. At day 18 of gestation, the placenta, liver, spleen and blood were harvested and litter size, number of viable fetuses and resorptions, maternal, fetal and placenta weights were recorded. For the direct inoculation group, some mice were allowed to deliver for assessment of length of gestation, litter size, maternal, placental and pup weight. The presence of Fn was assessed by PCR and inflammatory mediators were measured by ELISA or multiplex analysis. Results: Mice with alveolar bone loss, a marker of periodontitis, demonstrated significantly higher fetal weights (p = 0.015) and fetal/placental weight ratios (p = 0.030). PCR analysis of maternal organs did not identify Fn in any extracted tissues. In mice that received direct injection of Fn subspecies, varying degrees of APO were observed including preterm birth, intrauterine growth restriction, and fetal loss. Haematogenous spread of only Fn subsp. nucleatum to the placenta was confirmed. Litter size was significantly smaller (p = 0.023) and the number of resorptions was higher in inoculated versus control groups. Mice injected with subsp. nucleatum had significantly increased circulating CRP levels (p = 0.020) compared to controls while the mice with induced periodontitis had increased levels of IL-6 (p = 0.047) and IL-8 (p = 0.105). Conclusions: Periodontitis in mice elevated fetal weight and the fetal weight/placental weight ratio. This study found that subsp. nucleatum migrated haematogenously to the placenta, leading to APO in mice. The study supports the potential role of Fn in the association between periodontitis and APO. [ABSTRACT FROM AUTHOR]

Background: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery., Methods: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis., Results: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects., Conclusion: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au)., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.