Search Results (159)

Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article

Background/Objectives: Sleeve and wedge bronchial resections without removal of lung tissue may represent a surgical option in selected cases of low-grade neoplasms. This study is a retrospective analysis of the surgical technique and the short- and long- term results of bronchial sleeve resections performed in the Department of Thoracic Surgery of Careggi Hospital in Florence, Italy, and in the Department of Thoracic Surgery of Marie Lannelongue Hospital in Plessis Robinson, France. Methods: Between January 2017 and October 2024, 25 patients with low-grade tumors underwent bronchial sleeve resection with total lung-sparing. We collected the preoperative data, surgical techniques, postoperative results and long-term oncologic outcomes. Results: We performed 25 bronchial sleeves which resulted in 20 typical carcinoids (TC), 3 atypical carcinoids (AT) and 2 mucoepidermoid carcinomas. Three patients had R1 resection, and one of them also had N1 disease; a multidisciplinary team opted for a “watch and wait” policy without adjuvant therapies. No local recurrences occurred, although three distant recurrences were observed. The five-year overall survival (OR) rate was 100%; the five-year disease-free survival (DFS) rate was 80%. Conclusions: Bronchoplastic procedures without lung parenchyma resection are an appropriate and feasible technique for selected cases of low-grade endobronchial neoplasms. Full article

Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC). Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous. Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22–735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a “butyrate-rich” baseline profile was 44% (95% CI 35–54) versus 21% (95% CI 15–29) in controls (I² = 18%). Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment. Full article

Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n = 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p < 0.01) and EpCAM (p < 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5, p < 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making. Full article

Background: Rural patients, including those with rectal cancer, continue to be underrepresented in research and medically underserved with unique challenges to accessing care. Like the rest of America, rural patients are experiencing rising rates of rectal cancer; however, unlike the rest of the country, they also have rising rectal cancer-related mortality. This study aims to review the literature regarding care for patients with rectal cancer in rural settings, from presentation and diagnosis to treatment algorithms, oncologic outcomes, their unique preferences, and the goals of care. Methods: A literature search was performed on PubMed, on 31 October 2024, using synonyms of “rural” and “rectal cancer” to identify relevant articles. Articles from outside the USA and Canada and those offering only commentary were eliminated during the initial screening/retrieval. A full-text review was performed on the remaining articles; all the studies that did not address the identified primary or secondary outcomes in rural rectal cancer patients were then excluded. All the primary and secondary outcomes are briefly summarized in narrative form, with more detail on the primary outcomes provided in tables. The variability in the key criteria between the studies is also summarized in the tables and appendices provided. Results: Thirty studies were identified that addressed the outcomes of interest in rural rectal cancer patient populations. The total number of participants could not be assessed given the use of overlapping databases. Of the articles, 21 addressed treatment modalities (surgery, chemotherapy, radiation), 13 addressed oncologic outcomes, and a mix of additional studies addressed the diagnostic work up, costs, and patient preferences. The studies addressing treatment demonstrated similar practices in regard to chemotherapy and surgical management, aside from lower rates of minimally invasive surgery, along with decreased neoadjuvant radiotherapy use and increased under-dosing in rural patients. The oncologic outcomes were overall similar to worse for rural patients as compared to urban patients, even for those receiving treatment at high-volume urban centers. Additionally, rural patients have higher healthcare costs for rectal cancer care. Discussion/Conclusions: Rural patients are an at-risk group, with a rising disease burden and worsening rectal cancer outcomes, despite advances in rectal cancer care and improving oncologic outcomes in the general population. Analysis of the situation is complicated due to the underrepresentation of rural patients in research and the lack of uniformity in the definition of “rural”. Moreover, significant gaps in the literature remain, such that the evaluation of guideline-concordant care is incomplete, including an absence of literature about watch-and-wait approaches in rural populations. While regionalization of rectal cancer care has shown promise, the improvements in outcomes may not be commensurate for rural patients. Thus, a specific focus on the impact of this shift for rural patients is necessary to mitigate unintended consequences. Full article

Purpose: Organ preservation (OP) is an increasingly recognized treatment for locally advanced rectal cancer. However, variability in patient selection, treatment regimens, and surveillance can hinder widespread adoption. We conducted a national, cross-sectional survey evaluating how OP is implemented across Canada. Methods: Between June and July 2023, surgeons, radiation oncologists, and medical oncologists with expertise in OP from all 44 Canadian radiation centers completed an electronic survey about the implementation of OP at their centers. Primary OP was defined as administering neoadjuvant therapy with the explicit goal of avoiding surgery. Secondary OP was defined as deferring planned surgery only when there was an unexpected yet sufficient clinical response. Results: Responses from 40 radiation centers (response rate 90.9%) identified that 20 (50.0%) offered primary and secondary OP, 11 (27.8%) offered only secondary, and 8 (20.0%) offered neither. The most common treatment in primary OP was chemoradiation with consolidation chemotherapy (17/20, 89.5%). When assessing the response in primary OP, endoscopic biopsies were more commonly performed with a near-complete response (10/20, 50.0%) than a complete response (4/20, 20.0%). Watch-and-wait surveillance was more frequently offered for a complete response (17/31, 54.8%) than a near-complete response (4/31, 12.9%). Challenges included limited MRI (21/40, 52.5%), clinic time (18/40, 45.0%), timely surgery if required (16/40, 40.0%), and limited familiarity with the protocols and evidence (15/40, 37.5%). Conclusion: OP is recognized nationwide but is inconsistently implemented. Challenges raise concerns about the current feasibility of OP in Canada and highlight the need for less resource-intensive, complex OP protocols. Full article

Background and Clinical Significance: Ventricular septal defect (VSD) is a rare but serious complication following myocardial infarction (MI) that can lead to cardiogenic shock and carries a high mortality rate. Acute mitral regurgitation (MR) is another severe complication of MI with additional risks of mortality. The optimal timing of surgical intervention for VSD with MR is still being debated, and delaying surgery in medically manageable patients has been associated with improved survival. However, managing these patients in the intensive care unit (ICU) presents unique challenges. Case Presentation: In this paper, we present the case of a 52-year-old male with comorbidities who developed post-MI VSD with severe MR and underwent successful delayed surgical repair and mitral valve replacement. Our aim is to highlight the clinical characteristics, diagnostic approach, and management strategies of this rare complication in the critical care setting. The patient presented in cardiogenic shock and acute pulmonary edema. After stabilization using an intra-aortic balloon pump, pre- and afterload reducing pharmacotherapy and non-invasive mechanical ventilation, a watchful waiting strategy was employed, and surgery was performed on day 21 after hospital admission. Surgery was performed under general anesthesia, and the patient did not develop any complications related to the intra-aortic balloon pump or novel organ dysfunction. Conclusions: This case highlights the importance of a multidisciplinary approach to managing post-MI VSD with MR and emphasizes the need for careful patient selection and timing of surgical intervention in the critical care setting. Clinicians should be aware of the potential benefits of delaying surgical intervention in medically manageable patients, while also considering the unique challenges of managing these patients in the ICU. Full article

Background/Objectives: With recent advancements in rectal cancer management leading to longer patient survival, the impact of various treatment approaches on patients’ quality of life (QOL) becomes an important focus of attention. While QOL studies exist for watch-and-wait after (chemo)radiation with/without local excision, data on health-related QOL (HRQOL) outcomes after contact X-ray brachytherapy (CXB) remain limited. This study evaluated functional and HRQOL outcomes in rectal cancer patients undergoing CXB and (chemo)radiation over one year. Methods: This prospective observational study (enrolment January–October 2023) with one-year follow-up assessed functional and HRQOL outcomes after CXB and (chemo)radiation using EORTC-QLQ-CR29, HADS, and EQ-5D-3L questionnaires. Longitudinal analyses were conducted using linear mixed-effects models, incorporating both fixed and random effects, following data processing based on relevant scoring manuals. Results: QOL was assessed in 53 patients who attended our centre for CXB for various clinical indications, with 51, 47, and 42 remaining at the end of treatment, 6-month, and 12-month follow-ups, respectively. Overall, symptom and functional scores from EORTC-QLQ-CR29 remained stable throughout the follow-up period. Significant improvements were observed in abdominal pain, flatulence, urinary frequency, and body weight at 12 months. HADS and EQ-5D-3L scores remained stable, while EQ-VAS scores showed improvement, indicating a good overall quality of life following CXB treatment. Conclusions: CXB treatment combined with (chemo)radiation maintained stable HRQOL, with some improvements in symptoms and QOL noted during the subsequent year. These findings will help rectal cancer patients understand the benefits and limitations of CXB as a treatment option. Full article

Purpose: The aim of this review is to provide a contemporary update on the current management approaches and options with specific considerations in malignant rectal polyps. Methods: A literature review was carried out in PubMed, Embase and Cochrane databases using the keywords “malignant” and “polyp*”. Only publications in English language were included. Results: Histopathological features including margins, depth of invasion, tumour grade, LVI and tumour budding determines the risk of lymph node metastasis in malignant polyps. Rectal malignant polyps should be considered differently compared to their colonic counterpart. A low threshold should be considered for utilising transrectal excision to fully excise the polyp and to assess the margins. The rates of complete pathological response associated with total neoadjuvant therapy as well as the advent of “watch and wait” adds to the complexity of managing malignant rectal polyps. Conclusions: The management of malignant colorectal polyps lies in risk-stratifying patients who will benefit from an oncological resection. Full article

Desmoid tumors are rare mesenchymal neoplasms arising from locally invasive fibroblasts. While they lack metastatic potential, they exhibit high local recurrence rates and can cause significant tissue destruction. We present the case of a 39-year-old female patient who initially presented with epigastric pain, pyrosis, and a palpable, firm, painless mass in the left upper quadrant, extending to the left hemithorax. The patient’s medical history included treated cervical neoplasia. Clinical evaluation, imaging studies, and histopathological analysis suggested aggressive fibromatosis. The patient opted for a surgical excision, which resulted in tumor recurrence one year later, with infiltration of the ribs near the sternum. Despite oncological recommendations favoring conservative management, the patient opted for a second surgical intervention, involving an en-bloc resection of the tumor and the affected sternum and ribs, followed by thoracic wall reconstruction. Full article

Background/Objectives: The management of locally advanced rectal cancer has evolved significantly, shaped by advances in multimodal neoadjuvant therapy and a growing emphasis on organ preservation through the watch-and-wait approach. These advancements, however, introduce complex treatment decisions that require careful consideration by both patients and clinicians. Methods: This narrative review explores the evolution of the management of locally advanced rectal cancer and the role of shared decision-making in guiding treatment decisions, particularly for patients facing decisions between surgical resection and watch-and-wait. Additionally, it discusses the development of tools to aid in shared-decision making, current challenges in implementing shared decision-making and future directions for improvement patient centered care in locally advanced rectal cancer management. Results: Considerations for decision making include anatomical considerations that influence surgical options, the potential benefits and risks of watch-and-wait versus surgical resection of the rectum, and the impact of treatment on bowel, urinary, and sexual function. Additionally, patients must weigh the long-term implications of their choices on quality of life. Conclusions: Shared decision-making has emerged as a critical component of patient-centered care and ensures that treatment decisions align with patients’ values and priorities. Given the preference-sensitive nature of the management of locally advanced rectal cancer, shared decision-making plays an important role in helping patients navigate these decisions. Full article

Aortic stenosis is a progressive condition with substantial implications for morbidity and mortality. In recent years, attention has shifted toward risk stratification and the development of individualized management plans to optimize treatment outcomes. The management of asymptomatic patients has become a topic of significant controversy, as emerging studies challenge traditional watchful waiting guidelines and propose the potential benefits of early intervention. While early intervention may reduce overall morbidity and mortality in this patient population, the associated procedural risks remain a critical consideration. This review seeks to analyze the existing literature, offering an updated perspective on patient risk stratification and evidence evaluating both management approaches. Full article

Background and Objectives: Subthreshold depression (StD) presents with depressive symptoms similar to major depressive disorder (MDD) but of lower intensity. Despite its milder form, StD is significantly prevalent in the older population, affecting up to 12.9%. StD is associated with adverse outcomes, such as an increased risk of MDD and mild cognitive impairment (MCI). Treating StD in older adults is challenging due to the limited efficacy and side effects of traditional antidepressants. As a result, clinicians often adopt a “watchful waiting” strategy, which increases the risk of StD progressing into MDD or MCI. Choline alphoscerate (α-GPC), a cholinergic drug, is indicated in the treatment of pseudodepression in the elderly, a condition that corresponds to the actual definition of StD. This review highlights the role of α-GPC in the treatment of StD in older subjects. Methods: A comprehensive review of preclinical and clinical studies was conducted, focusing on the efficacy of α-GPC in improving cognitive and behavioral functions in mental conditions and in modulating neurotransmitter systems involved in depression, such as dopamine and serotonin. Results: Evidence points to the therapeutic benefits of using α-GPC in StD as it acts on cholinergic dysfunction and cognitive impairment. Additionally, it may improve mood regulation and motivation, key factors in StD and in depressive disorders. These findings suggest that α-GPC may reduce the risk of progression from StD to MDD or MCI. Conclusions: α-GPC represents an effective and safe therapeutic option for the treatment of StD in the older population, improving clinical outcomes and enhancing the quality of life in this high-risk group. Full article

Background: Patients with low tumour burden follicular lymphoma (FL) are managed with an initial watchful waiting (WW) approach. The way to better predict the time-to-treatment (TTT) is still under investigation for its possible clinical impact. This study explored whether radiomic features extracted from baseline ¹⁸F-FDG PET/CT could predict TTT in FL patients on WW. Methods: Thirty-eight patients on initial WW (grade 1–3a) were retrospectively included from 2010 to 2019. Eighty-one PET/CT morphological and first-level intensity radiomic features were extracted from the total metabolic tumour burden (TMTV), the lesion having the highest SUVmax and a reference volume-of-interest placed on the healthy liver. Models using linear regression (LR) and support vector machine (SVM) were constructed to assess the feasibility of using radiomic features to predict TTT. A leave-one-out cross-validation approach was used to assess the performance. Results: For LR models, we found a root-mean-squared error of 29.4, 28.6, 26.4 and 26.8 and an R² of 0.03, 0.08, 0.21 and 0.20, respectively, incrementing the features from one to four. Accordingly, the best model included three features: the liver minimum SUV value, the liver SUV skewness and the sum of squared SUV values in the TMTV. For SVM models, accuracies of 0.79, 0.63, 0.76 and 0.68 and areas under the curve of 0.80, 0.72, 0.77 and 0.63 were found, respectively, incrementing the features from one to four. The best performing model used one feature, namely the median value of the lesion containing the SUVmax value. Conclusions: The baseline PET/CT radiomic approach has the potential to predict TTT in FL patients on WW. Integrating radiomics with clinical parameters could further aid in patient stratification. Full article