Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Comparing outcomes and cost in surgery versus watch & wait surveillance of patients with rectal cancer post neoadjuvant long course chemoradiotherapy.

BACKGROUND: Watch and wait (W&W) in complete clinical responders after neoadjuvant chemoradiotherapy has increasingly robust data supporting its oncological safety. Recently, studies have assessed the real-world costs of this strategy compared to surgical resection. Our aim was to compare our oncological safety and costs associated with operative and surveillance strategies to international literature. METHODS: Data were retrospectively collected and analysed via electronic health records from March 2014 to March 2021 in Christchurch, New Zealand. Two cohorts were created based on intention to treat. All hospital events were recorded and costed, as well as oncologic outcomes. Our primary endpoints were the cumulative cost of both strategies, 3-year survival rate, and disease-free survival. RESULTS: Forty-eight patients were identified who had rectal cancers resected (OT) with a yPT0N0 pathology, and 42 who were on the wait-and-watch (W&W) audit after having a clinical complete response. After exclusions, we identified 38 OT and 23 W&W patients; the W&W group were more co-morbid (P = 0.05), had worse functional status (P = 0.008), higher BMI (P = 0.34) and more favourable clinical tumour staging (P = 0.01). The operative treatment (OT) group (n = 38) had more acute admissions (34% versus 13% in W&W, P = 0.08, OR 0.29). There was a 35.7% (n = 8 of 23) local recurrence in W&W and none in the OT group (P ≤ 0.001), with successful salvage in the W&W with local recurrence in 71.5% (n = 5 of 7). Three-year distant metastasis-free rate was 97.3% in the OT group and 90.9% in W&W (p = 0.05). Overall survival was 100% (W&W) and 94.7% (OT); (P = 0.019). Care in the OT group cost more than W&W, accounting for local regrowth management; $NZ70,759.56 versus $NZ47,905.52 (P = 0.014). CONCLUSION: This study found better oncological outcomes in the OT group, whilst the W&W group had reduced morbidity and acute bed days. The cost of wait and watch was approximately two-thirds that of operative treatment, even accounting for salvage procedures for local regrowth.

Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db/db Mice.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db/db mice (17-week-old) were orally administrated with OP (200 mg/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+/K+ transporting subunit alpha 3, which was enriched in the cGMP-PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.

Accuracy of deep neural learning models in the imaging prediction of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review.

PURPOSE: Up to 15-27% of patients achieve pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). Deep neural learning (DL) algorithms have been suggested to be a useful adjunct to allow accurate prediction of pCR and to identify patients who could potentially avoid surgery. This systematic review aims to interrogate the accuracy of DL algorithms at predicting pCR. METHODS: Embase (PubMed, MEDLINE) databases and Google Scholar were searched to identify eligible English-language studies, with the search concluding in July 2022. Studies reporting on the accuracy of DL models in predicting pCR were selected for review and information pertaining to study characteristics and diagnostic measures was extracted from relevant studies. Risk of bias was evaluated using the Newcastle-Ottawa scale (NOS). RESULTS: Our search yielded 85 potential publications. Nineteen full texts were reviewed, and a total of 12 articles were included in this systematic review. There were six retrospective and six prospective cohort studies. The most common DL algorithm used was the Convolutional Neural Network (CNN). Performance comparison was carried out via single modality comparison. The median performance for each best-performing algorithm was an AUC of 0.845 (range 0.71-0.99) and Accuracy of 0.85 (0.83-0.98). CONCLUSIONS: There is a promising role for DL models in the prediction of pCR following neoadjuvant-CRT for LARC. Further studies are needed to provide a standardised comparison in order to allow for large-scale clinical application. PROPERO REGISTRATION: PROSPERO 2021 CRD42021269904 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269904 .

The impact of short-course hypofractionated radiotherapy on multimodality treatment utilisation, compliance, and outcome in glioblastoma patients: a Danish patterns of care study.

BACKGROUND: The aim of this retrospective registry-based Danish patterns of care study was (1) to evaluate the real-world utilisation of short-course hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) patients over time, and (2) to evaluate the impact of short-course HFRT by assessing trends in multimodality treatment utilisation, compliance, and outcome. MATERIAL AND METHODS: Data of all adults with newly diagnosed pathology-confirmed GBM between 2011 and 2019 were extracted from the nationwide Danish Neuro-Oncology Registry. Short-course HFRT was defined as a fraction size of > 2 Gy to a planned dose of > 30 Gy. Patterns of care were assessed. To analyse trends in the assignment to short-course HFRT, and in radiotherapy (RT) compliance, multivariable logistic regression was applied. To analyse trends in survival, multivariable Cox regression was used. RESULTS: In this cohort of 2416 GBM patients, the utilisation of short-course HFRT significantly increased from ca. 10% in 2011 to 33% in recent years. This coincided with the discontinued use of palliative regimens and a decreased use of conventional fractionation. The proportion of patients proceeding to RT remained stable at ca. 85%. The proportion of patients assigned to chemoradiotherapy (CRT) remained stable at ca. 60%; the use of short-course hypofractionated CRT increased with ca. 10%, while the use of conventionally fractionated CRT decreased with ca. 10%. Compliance with conventionally fractionated and short-course HFRT was respective 92% and 93%, and significantly increasing in recent years. In the complete cohort, the median overall survival remained stable at ca. 11 months. Assignment to short-course HFRT was independently associated with shorter survival. CONCLUSION: In Denmark, the use of short-course HFRT significantly increased in recent years. Nonetheless, the overall utilisation of RT and chemotherapy did not increase on a population level. Nor did survival change. In contrast, compliance with both conventionally fractionated RT and short-course HFRT increased.

Short vs long-course antibiotic therapy in adults with acute cholangitis: A systematic review, meta-analysis, and evidence quality assessment.

BACKGROUND: Acute cholangitis (AC) constitutes an infection with increased mortality rates in the past. Due to new diagnostic tools and therapeutic methods, the mortality of AC has been significantly reduced nowadays. The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection. However, the optimal duration of the antibiotic treatment of AC is still debatable. AIM: To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC. METHODS: This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence. The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Fifteen studies were included in the systematic review, and eight were eligible for meta-analysis. Due to heterogeneous duration cutoffs, three study-analysis groups were formed, with a cutoff of 2-3, 6-7, and 14 d. RESULTS: A total of 2763 patients were included in the systematic review, and 1313 were accounted for the meta-analysis. The mean age was 73.66 ± 14.67 years, and the male and female ratio was 1:08. No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d, compared to longer treatments (odds ratio = 0.78, 95% confidence interval: 0.23-2.67, I2 = 9%) and the recurrence rates and hospitalization length were also not different in all study groups. CONCLUSION: Short- and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC. Safe conclusions cannot be extracted concerning the hospitalization duration.

Short-Term Outcomes and Cost-Effectiveness between Long-Course Chemoradiation and Short-Course Radiotherapy for Locally Advanced Rectal Cancer.

PURPOSE: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. MATERIALS AND METHODS: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. RESULTS: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. CONCLUSION: SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

Total neoadjuvant treatment and PD-1/PD-L1 checkpoint inhibitor in locally advanced rectal cancer.

For local advanced rectal cancer (LARC), total neoadjuvant treatment (TNT) has shown more complete response (CR), reduced risk of distant metastasis (DM) and increase of the sphincter preservation rate. Now it is the one and only recommendation for high-risk group of LARC according to National Comprehensive Cancer Network (NCCN) rectal cancer guideline, while it is also preferentially recommended for low-risk group of LARC. TNT is also beneficial for distant rectal cancer patients who have need for organ preservation. Even though the prognostic value of programmed cell death-ligand 1 (PD-L1) in the neoadjuvant chemoradiotherapy (NACRT) of LARC patients is undetermined yet, the combination of NACRT and programmed cell death-1 (PD-1)/PD-L1 antibodies seem bring new hope for mismatch repair proficient (pMMR)/microsatellite stable (MSS) LARC patients. Accumulating small sample sized studies have shown that combining NACRT with PD-1/PD-L1 antibody yield better short-term outcomes for pMMR/MSS LARC patients than historic data. However, ideal total dose and fractionation of radiotherapy remains one of unresolved issues in this combination setting. Thorough understanding the impact of radiotherapy on the tumor microenvironment and their interaction is needed for in-depth understanding and exquisite design of treatments combination model.

Patient-reported Bowel Function and Bowel-related Quality of Life After Pelvic Radiation for Rectal Adenocarcinoma: The Impact of Radiation Fractionation and Surgical Resection.

INTRODUCTION: Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited. METHODS: Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management. RESULTS: Of 204 patients surveyed, 124 (60.8%) responded. Median (interquartile range) time from radiation to survey completion was 30.1 (18.3-43) months. Seventy-nine (63.7%) respondents received LCRT, and 45 (36.3%) received SCRT; 101 (81.5%) respondents underwent surgery, and 23 (18.5%) pursued nonoperative management. There were no differences in LARS, FIQoL or FACT-G7 between patients receiving LCRT versus SCRT. On multivariable analysis, only nonoperative management was associated with lower LARS score signifying less bowel dysfunction. Nonoperative management and female sex were associated with a higher FIQoL score signifying less disruption and distress from fecal incontinence issues. Finally, lower BMI at the time of radiation, female sex, and higher FIQoL score were associated with higher FACT-G7 scores signifying better overall QOL. CONCLUSIONS: These results suggest long-term patient-reported bowel function and QOL may be similar for individuals receiving SCRT and LCRT for the treatment of LARC, but nonoperative management may lead to improved bowel function and QOL.

Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy.

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).

STAR-TREC: An International Three-arm Multicentre, Partially Randomised Controlled Trial Incorporating an External Pilot.

AIM: Organ saving treatment for early-stage rectal cancer can reduce patient reported side effects compared to standard total mesorectal excision (TME) and preserve quality of life (QOL). An optimal strategy for achieving organ preservation and longer-term oncological outcomes are unknown, thus there is a need for high quality trials. METHOD: Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC) is an international 3-arm multi-centre, partially randomised controlled trial incorporating an external pilot. In phase III, patients with cT1-3b N0 tumours, ≤40mm in diameter, who prefer organ preservation are randomised 1:1 between mesorectal long course chemoradiation versus mesorectal short course radiotherapy, with selective transanal microsurgery. Patients preferring radical surgery receive TME. STAR-TREC aims to recruit 380 patients to organ preservation and 120 to TME surgery. The primary outcome is the rate of organ preservation at 30 months. Secondary clinician reported outcomes include acute treatment-related toxicity, rate of non-operative management, non-regrowth pelvic tumour control at 36 months, non-regrowth disease free survival at 36 months, and overall survival at 60 months and patient reported toxicity, health related QOL at baseline, 12 and 24 months. Exploratory biomarker research uses circulating tumour DNA to predict response and relapse. DISCUSSION: STAR-TREC will prospectively evaluate contrasting therapeutic strategies and implement new measures including a smaller mesorectal target volume, 2-step response assessment and non-operative management for complete response. The trial will yield important information to guide routine management of patients with early-stage rectal cancer.

Watch and wait for Rectal Cancer: A 9 year Experience.

Background: Neoadjuvant long course chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. It can reduce tumour bulk, downstage, reduce the risk of local recurrence, and increase the possibility of clear resection margins. The aim of our study is to evaluate all patients over a 9 year period who underwent neoadjuvant chemoradiotherapy for rectal cancer and entered our watch and wait programme. Methods: Data were analysed from a prospective database for all patients diagnosed with rectal cancer over a 9 year period (2011-2019 inclusive). Findings: Over a 9 year period, 532 patients were treated for rectal cancer, with 180 patients receiving long course chemoradiotherapy. 61 (11%) patients entered a watch and programme as they had a complete clinical and radiological response following chemoradiotherapy. Within this programme, 40 patients (65%) remain disease free over the follow-up period (mean 38 months); 12 (20%) patients had regrowth and proceeded to surgery; and 9 (15%) proceeded to palliation due to being unfit for surgery or had distant metastatic disease. Overall (all cause) mortality was 18% during follow-up period in the watch and wait group. Conclusions: Neoadjuvant long course chemoradiotherapy is the standard treatment for locally advanced rectal cancer. 34% of our patient group who received long course chemoradiotherapy entered a watch and wait programme with the majority avoiding major rectal surgery.

Current Practice Patterns in Locally Advanced Rectal Cancer at Academic Institutions: A National Survey Among Radiation Oncologists, Medical Oncologists, and Colorectal Surgeons.

PURPOSE: To assess the current treatment patterns in locally advanced rectal cancer (LARC) among radiation oncologists (RO), medical oncologists (MO), and colorectal surgeons (SR) specializing in gastrointestinal (GI) malignancies at academic institutions. MATERIALS AND METHODS: An online survey consisting of 7 LARC clinical vignettes was distributed to GI specialists practicing at ACGME accredited academic institutions. Treatment paradigms consisted of long-course chemoradiation (LC-CRT) and short-course (SCRT) radiotherapy, chemotherapy (CHT), and surgery. The survey was open from January to April 2021. RESULTS: Thirty-six RO, 14 MO and 21 SR (71/508 physicians) replied resulting in a response rate of 14.0%. For low rectal node positive tumors, 88.7% of primary recommendations incorporated TNT (73.1% LC-CRT, 26.9% SCRT). NOM was preferred by 41.3% if a clinical complete response (cCR) was achieved. The presence of high-risk features led 95.8% of physicians to employ TNT (79.4% LC-CRT, 20.6% SCRT). For a cT3N1-2 mid-rectal tumor without high-risk features, 85.9% would primarily recommend TNT (56.6% LC-CRT, 43.4% SCRT). For a cT4bN2a mid-rectal tumor without high-risk features, 97.2% of primary recommendations included TNT (76.9% LC-CRT, 23.1% SCRT). CONCLUSION: Among academic RO, MO, and SR, the traditional regimen of LC-CRT, surgery, and adjuvant CHT is now infrequently recommended for LARC. TNT has been widely adopted for locally advanced node positive rectal tumors with variable patterns of care with respect to sequencing of CHT and RT. Fractionation with LC-CRT remained the majority. Non-operative management after a cCR in low rectal tumors has gained traction transforming LARC from a once classically perceived surgical disease.

Current status of neoadjuvant therapy for locally advanced rectal cancer in Wuhan Union Hospital Cancer Center.

BACKGROUND: To analyze and explore the evolution and short-term efficacy of neoadjuvant therapy for patients with mid and low LARC in Wuhan Union Hospital Cancer Center. METHODS: Patients diagnosed with rectal cancer from January 2015 to December 2021 were collected. The treatment patterns, short-term efficacy and treatment-related adverse events (AEs) of mid and low LARC patients who received neoadjuvant therapy were analyzed. The Chi-square test was used to compare the differences between groups. RESULTS: A total of 980 patients with mid and low LARC were enrolled, over time, the proportion of patients receiving neoadjuvant therapy gradually increased, and the treatment mode of direct surgery after diagnosis was gradually watered down. More than 80% of the patients implemented radiotherapy-based neoadjuvant therapy, and the proportion of patients receiving SCRT sequential systemic therapy gradually exceeded that of LCRT combined chemotherapy after 2020. Of all patients who completed radiotherapy and underwent surgery, 170 patients received long-course chemoradiotherapy (LCRT) combined with chemotherapy (Group C) and 98 patients received short-course radiotherapy (SCRT) combined with systemic therapy (chemotherapy with or without immunotherapy) (Group D). The pathological complete response (pCR) rate in Group D was significantly higher than that in Group C (38.8% vs. 19.4%, P = 0.001). The pCR rate in the SCRT plus immunotherapy group was better than that in the group without immunotherapy (49.2% vs. 21.6%, P = 0.007). 82.3% of the patients receiving immunotherapy were treated with SCRT sequential 2-cycle CapOX plus Camrelizumab treatment, and the pCR was as high as 52.9%. Immunotherapy did not increase the incidence of Grade 3-4 AEs. CONCLUSIONS: Neoadjuvant therapy based on radiotherapy is becoming used in patients with mid and low LARC. SCRT sequential systemic therapy is increasingly widely used in LARC patients in our center. Compared with the traditional LCRT or SCRT sequential chemotherapy, SCRT sequential chemotherapy plus immunotherapy has a remarkable pCR rate and manageable toxicity. Looking forward this new treatment mode will bring lasting survival benefits to patients.

The Potential for Overtreatment With Total Neoadjuvant Therapy (TNT): Consider One Local Therapy Instead.

With increased therapeutic options in rectal cancer, a central question has become how to tailor therapy to patient preferences to avoid both over and under treatment. Total Neoadjuvant Therapy (TNT), defined as delivering all planned chemotherapy and radiation therapy (RT) before surgery, was developed with the primary goal of improving overall survival through early elimination of micrometastatic disease. In this narrative review assessing patients with operable adenocarcinoma of the rectum, we sought to evaluate TNT versus alternative options with regard to both quality of life (QoL) and oncologic outcomes. Survey data of patient preferences reveal that an increased focus on QoL when discussing options is essential. While evidence favors TNT improving distant metastases-free survival, this has not yet translated to a clear OS benefit. The improved pathologic complete response rate with TNT compared to short course RT or chemoradiation alone suggests proceeding to surgery might result in overtreatment, lending support to a watch-and-wait option for patients with a goal for nonoperative management if a clinical complete response is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. In the treatment of rectal cancer, the future appears to be moving toward one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy instead: chemoradiation followed by consolidation chemotherapy, saving surgery only for incomplete responders rather than as part of the initial treatment plan. Also, selective use of RT should be considered for low-risk patients. By thoroughly assessing how these treatment de-escalation options compare to more traditional treatment algorithms, this narrative review provides guidance on how to honor patient preferences for QoL by avoiding treatments that might offer negligible benefits in oncologic outcomes.

High vs. Standard Radiotherapy Dose in Locally Advanced Rectal Adenocarcinoma Patients Treated With Neoadjuvant Long Course Chemoradiotherapy: A Population-based Study.

BACKGROUND/AIM: Locally advanced rectal cancer (LARC) patients are often treated with neoadjuvant long course chemoradiotherapy (NLCCRT) using 45-50.4 Gy conventional fractionated radiotherapy (CFRT). The role of radiotherapy dose escalation is unclear. PATIENTS AND METHODS: We identified LARC patients diagnosed from 2011 to 2016 and treated with NLCCRT using CFRT at high dose (54-60 Gy) or standard dose (45-50.4 Gy). In the primary analyses, we used propensity score (PS) weighting to balance the observable potential confounders. The hazard ratio (HR) of death and other endpoints were compared. We also evaluated these outcomes in supplementary analyses via an alternative approach. RESULTS: Our primary analysis included 459 patients. The HR of death when high dose was compared with standard dose was 0.62 (p=0.51). There were also no statistically significant differences in other endpoints or in the supplementary analyses. CONCLUSION: Overall, survival of LARC patients treated with NLCCT in CFRT was not significantly different between high or standard dose.

Trends in the use of short-course radiation therapy for rectal cancer in New South Wales, Australia.

INTRODUCTION: Trends in the use of short-course radiation therapy (RT) for rectal cancer in Australia are unknown. The purpose of this study was to compare short-course RT and long-course chemoradiation (CRT) utilisation in the neoadjuvant treatment of rectal cancer in New South Wales (NSW). METHODS: Patients who received neoadjuvant RT (2009-2014) for rectal cancer were identified from the NSW Central Cancer Registry. Univariate and multivariable analyses were performed to investigate factors associated with receipt of short-course RT. RESULTS: A total of 1196 (81%) patients received long-course CRT, and 274 (19%) patients received short-course RT. Receipt of short-course RT was associated with older age: 54% in patients ≥80 years, and 11% in patients <50 years (P < 0.0001). Patients with T2 disease (30%) were more likely to receive short-course RT, compared with T3 (19%) or T4 (8%) disease (P = 0.002). Patients with N0 (23%) disease were more likely to be treated with short-course RT, compared with N+ (16%) (P = 0.03). The proportion of short-course RT delivered to patients with Charlson Comorbidity Index (CCI) ≥ 2 (28%) was higher than patients with CCI = 0 (17%) (P = 0.002). There was wide variation in the proportion of short-course RT used across residence local health districts (5-29%) (P < 0.0001). CONCLUSION: In rectal cancer patients treated with neoadjuvant RT in NSW, 19% received short-course RT. The use of short-course RT was associated with older age, comorbidities and less advanced disease. Wide variation across NSW was identified and future research investigating factors for the variation will be useful.

MRI radiomics in the prediction of therapeutic response to neoadjuvant therapy for locoregionally advanced rectal cancer: a systematic review.

Introduction: The standard of care for locoregionally advanced rectal cancer is neoadjuvant therapy (NA CRT) prior to surgery, of which 10-30% experience a complete pathologic response (pCR). There has been interest in using imaging features, also known as radiomics features, to predict pCR and potentially avoid surgery. This systematic review aims to describe the spectrum of MRI studies examining high-performing radiomic features that predict NA CRT response.Areas covered: This article reviews the use of pre-therapy MRI in predicting NA CRT response for patients with locoregionally advanced rectal cancer (T3/T4 and/or N1+). The primary outcome was to identify MRI radiomic studies; secondary outcomes included the power and the frequency of use of radiomic features.Expert opinion: Advanced models incorporating multiple radiomics categories appear to be the most promising. However, there is a need for standardization across studies with regards to; the definition of NA CRT response, imaging protocols, and radiomics features incorporated. Further studies are needed to validate current radiomics models and to fully ascertain the value of MRI radiomics in the response prediction for locoregionally advanced rectal cancer.

Long course of polymyxin B for the treatment of brain abscess caused by carbapenem resistant Acinetobacter baumannii: a case report / 中华危重病急救医学

The clinical efficacy of polymyxins in severe infection caused by carbapenem resistant organism (CRO) has gradually been recognized, and the course of treatment is generally 2 to 4 weeks. The most common complications after intravenous injection are nephrotoxicity and neurotoxicity, however, there are few reports on the efficacy and safety of the long course use of polymyxins. A patient with carbapenem resistant Acinetobacter baumannii (CRAB) infection after neurosurgery was admitted to the department of neurosurgical intensive care unit (NICU) of Lanzhou University Second Hospital. As the family refused the excision of brain abscess and Ommaya reservoir placement, polymyxin B was given intravenous (3.0 mg·kg -1·d -1) combined with intrathecal (5 mg once daily) injection, and high-dose sulbactam (8 g/d) was intravenously injected for anti-infection therapy. Finally, the brain abscess was absorbed and the patient was successfully cured. The total course of polymyxin B was 69 days with a cumulative dosage of 7 500 mg. There were no complications such as polymyxin-related nephrotoxicity and neurotoxicity during the period, and no symptoms of respiratory inhibition or neuromuscular blockage were observed, but polymyxin-related skin pigmentation appeared about 1 month after intravenous administration of polymyxins B, which subsided after drug withdrawal. It is suggested that long course of polymyxins B is safe and effective for intracranial infection caused by CRAB.

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study.

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced "dysplastic-like" features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.