Molecular characterization of colorectal cancer related peritoneal metastatic disease.

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.

The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden.

Colorectal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and of patients with CPM not responding to treatment with CRS & HIPEC, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome (n = 25), epigenome (n = 24) and genome (n = 21) of CPM and matched primary CRC was performed. CPM were characterised by frequent Wnt/ ß catenin negative regulator mutations, TET2 mutations, mismatch repair mutations and high tumour mutational burden. Here we show the molecular features associated with CPM development and associated with not responding to CRS & HIPEC. Potential applications include improving patient selection for treatment with CRS & HIPEC and in future research into novel and personalised treatments targeting the molecular features identified here.

A Systematic Review of Local Excision After Neoadjuvant Therapy for Rectal Cancer: Are ypT0 Tumors the Limit?

BACKGROUND: Neoadjuvant therapy reduces local recurrence after radical surgery for rectal cancer with complete pathological response in 15% to 25% of patients. Radical surgery is associated with significant morbidity that may be avoided by local excision in selected cases. OBJECTIVE: This systematic review aimed to determine the oncological outcomes and morbidity of local excision after neoadjuvant therapy. DATA SOURCES: Data sources included MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases. STUDY SELECTION: A systematic search of the databases using validated terms for rectal cancer, neoadjuvant therapy, and local excision was conducted. INTERVENTIONS: Neoadjuvant therapy and local excision were the included interventions. MAIN OUTCOME MEASURES: Pooled local recurrence, median survival, and pooled morbidity were measured. RESULTS: Twenty unique studies were included (14 cohort, 5 comparative cohort, and 1 randomized controlled trial), describing 1068 patients. Patient choice, prohibitive comorbidity, good clinical response, and early stage disease were the most frequent indications for local excision. Pretreatment T2 and T3 tumors accounted for 46.4% and 30.7% of cases. Long-course treatment was administered in all of the studies, except to a cohort of 64 patients who received short-course radiotherapy. Pooled complete clinical response was 45.8% (95% CI, 31.4%-60.5%), and pooled complete pathological response was 44.2% (95% CI, 36.4%-52.0%). Median follow-up was 54 months (range, 12-81 months). ypT0 tumors had a pooled local recurrence rate of 4.0% (95% CI, 1.9%-6.9%) and a median disease-free survival rate of 95.0% (95% CI, 87.4%-100%). Pooled local recurrence and median disease-free survival rates for ypT1 tumors or higher were 21.9% (95% CI, 15.9%-28.5%) and 68.0% (58.3%-69.0%). Pooled incidence of complications was 23.2% (95% CI, 15.7%-31.7%), with suture-line dehiscence reported in 9.9% (95% CI, 4.8%-16.7%). LIMITATIONS: Limitations included study quality, high risk of selection bias and detection bias in study designs, and limited sample sizes. CONCLUSIONS: Local excision after neoadjuvant therapy should only be considered a curative treatment if complete pathological response is obtained. Given the high rate of local recurrence among incomplete responders, future studies should focus on predicting patients who will achieve complete pathological response.

Primary ectopic breast carcinoma in a supernumerary breast arising in the anterior chest wall: a case report and review of the literature.

Accessory mammary tissue occurs in 0.2-6% of women, and is under the same hormonal influences as breast tissue, potentially undergoing malignant transformation. Carcinomas of accessory mammary tissue account for ∼0.3% of breast cancers, 5% of which are within a supernumerary breast. Due to its rarity and the low index of clinical suspicion, it is often diagnosed at a later stage compared with breast cancer. Reports of carcinoma developing in a supernumerary breast are rare. We describe a case of a 48-year-old woman, presenting with ectopic breast carcinoma within a supernumerary breast below the inframammary fold. We describe the mode of presentation, diagnosis and treatment with reference to the available literature. The radiotherapy treatment plan is discussed in detail to provide reference for future cases as the available literature offers no formal guidance on radiotherapy dose, fractionation or treatment field.