Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

Colorectal Cancer in the Young: Research in Early Age Colorectal Cancer Trends (REACCT) Collaborative.

Background: The incidence of colorectal cancer (CRC) is increasing in the young (under 50). Defining the clinicopathological features and cancer-specific outcomes of patients with early-onset CRC is important to optimize screening and treatment strategies. This study evaluated disease-specific features and oncological outcomes of patients with early-onset CRC. Methods: Anonymized data from an international collaboration were analyzed. The inclusion criteria for this study were patients aged <50 years with stage I-III disease surgically resected with curative intent. Overall and disease-free survival were calculated using the Kaplan-Meier method. Results: A total of 3378 patients were included, with a median age of 43 (18-49) and a slight male preponderance (54.3%). One-third had a family history of colorectal cancer. Almost all (>95%) of patients were symptomatic at diagnosis. The majority (70.1%) of tumors were distal to the descending colon. Approximately 40% were node positive. Microsatellite instability was demonstrated in one in five patients, representing 10% of rectal and 27% of colon cancers. A defined inherited syndrome was diagnosed in one-third of those with microsatellite instability. Rectal cancer displayed a worse prognosis stage for stage. Five-year disease-free survival for stage I, II, and III colon cancer was 96%, 91%, and 68%, respectively. The equivalent rates for rectal cancer were 91%, 81%, and 62%. Conclusions and relevance: The majority of EOCRC would be captured with flexible sigmoidoscopy. Extending screening to young adults and public health education initiatives are potential interventions to improve survivorship.

A systematic review of oncological outcomes after nipple-sparing mastectomy for breast cancer.

Nipple-sparing mastectomy is an alternative to skin-sparing mastectomy in select patients. Increasing evidence supports its use in the setting of breast cancer, however concerns still exist regarding oncological safety. The aim of this systematic review was to evaluate long-term oncological outcomes of patients who underwent nipple-sparing mastectomy for breast cancer. A systematic review of the literature was performed to evaluate oncological outcomes in patients with breast cancer who underwent nipple-sparing mastectomy. Five major databases (PubMed, Embase, Scopus, Web of Science and Cochrane) were searched. The review included all original articles published in English reporting long-term oncological outcomes. 2334 studies were identified. After applying inclusion and exclusion criteria, 17 retrospective studies involving 7107 patients were included. The indication for nipple-sparing mastectomy was invasive carcinoma in 6069 patients (85.4%) and in situ disease in 1038 (14.6%). Median follow up was 48 months (range 25-94). The weighted mean rates of local recurrence and recurrence involving the nipple-areola complex were 5.4% (0.9-11.9) and 1.3% (0-4.9), respectively. The weighted mean distant failure rate was 4.8% (1.5-23.0). Therapeutic nipple-sparing mastectomy is oncologically safe in select patients with breast cancer.

The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review.

Colorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Anastomotic leak risk in complete responders to neoadjuvant therapy for rectal cancer: a systematic review.

PURPOSE: The oncological benefits of achieving a complete pathological response following neoadjuvant chemoradiotherapy for rectal cancer are well defined. How a pathological response affects anastomotic healing or leak rates is not clear. The aim of this systematic review was to compare anastomotic leak rates among patients who did and did not achieve a complete pathological response. METHODS: Three major databases (PubMed, Embase, and Scopus) were searched. Predetermined inclusion criteria included prospective and retrospective articles published in English reporting complete pathological response and anastomotic leak rates following total mesorectal excision in ≥ 30 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and total mesorectal excision. The primary outcomes measured included complete pathological response and 30-day postoperative morbidity. RESULTS: From a total of 8919 patients with rectal cancer in 7 studies, 4165 fulfilled the criteria for inclusion. The majority (> 80%) of patients had clinical stage II or III disease. A defunctioning loop ileostomy was formed in 76.5%. A total of 589 (14.1%) patients achieved a pCR of whom 63 (10.7%) developed an anastomotic leak compared to 272/3576 (7.6%) patients without a pCR (p = 0.02). CONCLUSION: Patients with complete pathological response following neoadjuvant chemoradiotherapy and total mesorectal excision may be at higher risk of anastomotic leak than incomplete responders. This may need to be taken into account when counseling patients about the relative risks of organ preservation versus anterior resection.

Evidence-based treatment strategies for acute diverticulitis.

PURPOSE: Diverticular disease is a common acquired condition of the lower gastrointestinal tract that may be associated with significant morbidity. The term encompasses a spectrum of pathological processes with varying clinical manifestations. The purpose of this review was to update the reader on modern evidence-based treatment strategies for acute diverticulitis. METHODS: A literature search of the PUBMED database was performed using the keywords 'diverticulosis', 'diverticular disease' and 'diverticulitis'. Only articles published in the English language were included. RESULTS: Evidence-based treatment strategies for acute diverticulitis have evolved over time. Data have questioned the need for antibiotic therapy for Hinchey I disease and the role of percutaneous abscess drainage for Hinchey II. Clinical trials have demonstrated laparoscopic lavage is an appropriate option for select patients with Hinchey III disease and primary resection with anastomosis and defunctioning stoma may be considered in some cases of Hinchey IV disease. CONCLUSION: Risk-adapted treatment strategies and operative decision-making for acute diverticulitis are increasingly based on a combination of patient and disease factors.