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Background This study reports early mortality and survival from colorectal cancer in relation to the pattern of treatments delivered by the multidisciplinary team (MDT) meeting at a high-volume institution in England over 14 years. Methods All patients diagnosed with colorectal cancer and discussed during MDT meetings from 2003 to 2016 at a single institution were reviewed. Three time intervals (2003–2007, 2008–2012, and 2013–2016) were compared regarding initial surgical management (resection, local excision, non-resection surgery, and no surgery), initial oncological therapy, 90-day mortality, and crude 2-year survival for the whole cohort. Sub-analyses were performed according to age greater or less than 80 years. Results The MDT managed 4617 patients over 14 years (1496 in the first interval and 1389 in the last). Over this time, there was a reduction in emergency resections from 15.5 per cent to 9.0 per cent (P < 0.0001); use of oncological therapies increased from 34.6 per cent to 41.6 per cent (P < 0.0001). The 90-day mortality after diagnosis of colorectal cancer dropped from 14.8 per cent to 10.7 per cent (P < 0.001) and 2-year survival improved from 58.6 per cent to 65 per cent (P < 0.001). Among patients aged 80 years or older (425 and 446, in the first and last intervals respectively) there was, in addition, a progressive increase in 'no surgery' rate from 33.6 per cent to 50.2 per cent (P < 0.0001) and a reduction in elective resections from 42.4 per cent to 33.9 per cent (P = 0.010). The 90-day mortality after elective resection fell from 10.0 per cent (18 of 180) to 3.3 per cent (5 of 151; P = 0.013). Conclusions Survival from colorectal cancer improved significantly over 14 years. Among patients aged ≥80 years, major changes in the type of treatment delivered were associated with a decrease in postoperative mortality. [ABSTRACT FROM AUTHOR]

Cancer Rehabilitation: Why Can't We Get Out of First Gear? Because of advances in the diagnosis and treatment of some cancers, there are now more than five million cancer survivors [...]

Introduction: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are often used for benign and Sm1 large non-pedunculated rectal polyps (LNPRPs), although other surgical techniques including transanal endoscopic microsurgery (TEMS) and transanal minimal invasive surgery remain available. This review covers the role of pre-excisional imaging and selective biopsy of LNPRPs. Areas covered: Polyps between 2 and 3 cm with favorable features (Paris 1, Kudo III/IV pit patterns, and non-lateral spreading type [LST]) may have a one-stage EMR without biopsy and imaging, provided adequate expertise is available with other technologies such as magnifying chromoendoscopy. Higherrisk polyps (moderate/severe dysplasia, 0-IIa+c morphology, nongranular LST, Kudo pit pattern V or submucosal carcinoma, or those >3 cm) should have pre-EMR/ESD imaging with magnetic resonance imaging (MRI) and/or endorectal ultrasound (ERUS) ± biopsies and photographs prior to multidisciplinary team discussion. Expert commentary: In some centers, EMR and ESD are considered the primary modality of treatment, with TEMS as a back-up, while elsewhere, TEMS is the main modality for excision of significant polyps and early colorectal cancer lesions. Likewise, the exact roles of ERUS and MRI will depend on availability of local expertise, although it is suggested that the techniques are complementary. [ABSTRACT FROM AUTHOR]

The article focuses on a systematic review conducted by the authors related to identification of biomarkers for diagnosing colorectal cancer and polyps. Topics discussed include detection of the cancer through fecal DNA markers, serum protein biomarkers, high positive predictive value (PPV) of immunochemical fecal occult blood test (iFOBT) as compared to guaiac fecal occult blood test (gFOBT) and high cost involved in screening on the basis of biomarkers.

Colorectal cancer (CRC) is a major cause of mortality in western society with a 5-year survival of approximately 50%. Metastasis to the liver and lungs is the principal cause of death and occurs in up to 25% of patients at presentation. Despite advances in available techniques for treating metastases, the majority of patients remain incurable and existing adjuvant therapies such as chemotherapy are only of limited effectiveness. Understanding the molecular mechanisms underlying the metastatic process may allow us to identify those at greatest risk of recurrence and discover new tumour targets to prevent disease progression. It is now apparent that tumour stroma plays an important role in promoting tumour progression. A pronounced desmoplastic reaction was associated with a reduced immune response and has been shown to be an independent poor prognostic indicator in CRC and cancer recurrence. Determining the cause(s) and effect(s) of this stromal response will further our understanding of tumour cell/stromal interactions, and will help us identify prognostic indicators for patients with CRC. This will not only allow us to target our existing treatments more effectively, we also aim to identify novel and more specific therapeutic targets for the treatment of CRC which will add to our current therapeutic options. [ABSTRACT FROM AUTHOR]

B Background: b Up to 30% of patients with stage III disease have a recurrence by 5 years after "curative" surgery. The postoperative day 3 median neutrophil count of the patients that developed distant metastasis was 9.4(5.3-12.1)x10 SP 9 sp /L vs. 6.3(3.7-8.6)x10 SP 9 sp /L for the patients that didn't (p=0.048). B Conclusion: b We show some preliminary evidence, postoperative neutrophil count can be used as risk predictor of the development of distant metastasis in patients undergoing surgery for stage III rectal cancer, with a specificity of 90%, NPV81%. [Extracted from the article]

Non-hepatosplenic extramedullary hematopoiesis (NHS-EMH), the formation of blood cellular elements outside the medulla of the bone marrow and outside the liver and spleen, has been noted among patients with myeloproliferative neoplasms and other serious hematological diseases. However, NHS-EMH is rarely identified among individuals without concurrent hematological disease. Since the radiologic features of NHS-EMH are nonspecific, lesions may be mistaken for metastatic disease when observed in patients with known solid tumors. We report an unusual case of a patient with a simultaneous presentation of malignant melanoma and multiple NHS-EMH lesions. The biopsy revealed trilineage hematopoiesis resembling normal bone marrow tissue, in the absence of abnormalities of peripheral blood counts or presence of driver mutations associated with myeloproliferative neoplasms. The biopsy results were critical in downstaging the patient and thus permitted avoidance of unnecessary malignant melanoma therapy. This case emphasizes the importance of surgical biopsy of suspect lesions when treatment strategies will be impacted., Competing Interests: The authors have no conflict of interest to disclose., (Copyright 2022, Williams et al.)

Purpose: The treatment of metastatic colorectal carcinoma represents a major clinical challenge. We investigated the hypothesis that the desmoplastic reaction within the liver elicited by metastatic adenocarcinoma, characterized by collagen I deposition and altered collagen IV distribution, promotes the growth and survival of hepatic colorectal carcinoma metastases., Experimental Design: Partial hepatectomy specimens for metastatic colorectal adenocarcinoma were examined immunohistochemically for differential integrin expression. Human colorectal adenocarcinoma cell lines HT-29, KM12SM, and KM12c were grown on wild-type collagen I or IV, or cleavage-resistant r/r collagen I, and assessed for their growth, survival, and resistance to 5-fluorouracil. The effect of alpha(v)beta(3) and alpha(v)beta(5) integrin blockade by neutralizing antibodies was examined., Results: Collagen I, in contrast to collagen IV, significantly enhanced the growth, survival, and chemoresistance of colorectal carcinoma cells. Blockade of the alpha(v)beta(3) and alpha(v)beta(5) integrins significantly reduced colorectal carcinoma cell proliferation on collagen, especially in the cell line with the most metastatic potential. These in vitro findings correlated with the pattern of integrin expression identified within resected hepatic colorectal carcinoma metastases. Using matrix metalloproteinase-resistant r/r collagen I as a dominant negative ligand for alpha(v) integrins, we showed a key role for this integrin-ligand interaction in mediating the survival and proliferation of colorectal carcinoma cells., Conclusions: Desmoplasia has an important role in the development of hepatic colorectal carcinoma metastasis. The interaction between integrin and collagen I is identified as a potential therapeutic target.

Purpose: The purpose of this study was to determine the role of functional interactions between pancreatic cancer cells and pancreatic stellate cells (PSCs) in the formation of the desmoplastic reaction (DR) in pancreatic cancer and to characterize the effect of type I collagen (the predominant component of the DR) on pancreatic cancer cell phenotype., Experimental Design: PSCs and type I collagen were identified in sections of pancreatic cancer using immunohistochemistry, and their anatomic relationship was studied. Interactions among pancreatic cancer cell lines (MIA PaCa-2, Panc-1, and AsPC-1), primary cultures of human PSCs, and type I collagen were investigated in a series of tissue culture models., Results: In vivo, the DR causes gross distortion of normal pancreas, bringing cancer cells into close contact with numerous PSCs and abundant type I collagen. In tissue culture models of pancreatic cancer, conditioned media from each cell line increased PSC [3H]thymidine incorporation up to 6.3-fold that of controls, and AsPC-1 cells also increased PSC collagen synthesis 1.3-fold. Type I collagen was observed to increase long-term survival of pancreatic cancer cells treated with 5-fluorouracil, by up to 62% in clonogenic assays. This was because type I collagen increased the proliferation of cancer cells ([3H]thymidine incorporation was up to 2.8-fold that of cells cultured on tissue culture plastic) and reduced apoptosis of AsPC-1 cells in response to 5-fluorouracil (by regulating mcl-1)., Conclusions: These experiments elucidate a mechanism by which the DR in pancreatic cancer may form and, via the collagen within it, promote the malignant phenotype of pancreatic cancer cells, suggesting significant detriment to the host.