Changing patterns of multidisciplinary team treatment, early mortality, and survival in colorectal cancer.

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.

Non-Hepatosplenic Extramedullary Hematopoiesis Masquerading as Metastatic Malignant Melanoma.

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.

Factors Predicting Operative Difficulty of Laparoscopic Total Mesorectal Excision.

BACKGROUND: Laparoscopic total mesorectal excision is a challenging procedure requiring high-quality surgery for optimal outcomes. Patient, tumor, and pelvic factors are believed to determine difficulty, but previous studies were limited to postoperative data. OBJECTIVE: This study aimed to report factors predicting laparoscopic total mesorectal excision performance by using objective intraoperative assessment. DESIGN: Data from a multicenter laparoscopic total mesorectal excision randomized trial (ISRCTN59485808) were reviewed. SETTING: This study was conducted at 4 centers in the United Kingdom. PATIENTS AND INTERVENTION: Seventy-one patients underwent elective laparoscopic total mesorectal excision for rectal adenocarcinoma with curative intent: 53% were men, mean age was 69 years, body mass index was 27.7, tumor height was 8.5 cm, 24% underwent neoadjuvant therapy, and 25% had previous surgery. MAIN OUTCOME MEASURES: Surgical performance was assessed through the identification of intraoperative adverse events by using observational clinical human reliability analysis. Univariate analysis and multivariate binomial regression were performed to establish factors predicting the number of intraoperative errors, surgeon-reported case difficulty, and short-term clinical and histopathological outcomes. RESULTS: A total of 1331 intraoperative errors were identified from 365 hours of surgery (median, 18 per case; interquartile range, 16-22; and range, 9-49). No patient, tumor, or bony pelvimetry measurement correlated with total or pelvic error count, surgeon-reported case difficulty, cognitive load, operative data, specimen quality, number or severity of 30-day morbidity events and length of stay (all r not exceeding ±0.26, p > 0.05). Mesorectal area was associated with major intraoperative adverse events (OR, 1.09; 95%CI, 1.01-1.16; p = 0.015) and postoperative morbidity (OR, 1.1; 95% CI, 1.01-1.2; p = 0.033). Obese men were subjectively reported as harder cases (24 vs 36 mm, p = 0.042), but no detrimental effects on performance or outcomes were seen. LIMITATIONS: Our sample size is modest, risking type II errors and overfitting of the statistical models. CONCLUSION: Patient, tumor, and bony pelvic anatomical characteristics are not seen to influence laparoscopic total mesorectal excision operative difficulty. Mesorectal area is identified as a risk factor for intraoperative and postoperative morbidity. See Video Abstract at http://links.lww.com/DCR/B35. FACTORES QUE PREDICEN LA DIFICULTAD OPERATIVA DE LA ESCISIÓN MESORRECTAL TOTAL LAPAROSCÓPICA: La escisión mesorrectal total laparoscópica es un procedimiento desafiante. Para obtener resultados óptimos, se requiere cirugía de alta calidad. Se cree que, factores como el paciente, el tumor y la pelvis, determinan la dificultad, pero estudios previos solamente se han limitado a datos postoperatorios.Informar de los factores que predicen el resultado de la escisión mesorrectal total laparoscópica, mediante una evaluación intraoperatoria objetiva.Datos de un ensayo multicéntrico y randomizado de escisión mesorrectal total laparoscópica (ISRCTN59485808).Cuatro centros del Reino Unido.Un total de 71 pacientes fueron sometidos a escisión mesorrectal total laparoscópica electiva, para adenocarcinoma rectal con intención curativa. 53% hombres, edad media, índice de masa corporal y altura del tumor 69, 27.7 y 8.5 cm respectivamente, 24% terapia neoadyuvante y 25% cirugía previa.Rendimiento quirúrgico evaluado mediante la identificación de eventos intraoperatorios adversos, mediante el análisis clínico observacional de confiabilidad humana. Se realizaron análisis univariado y la regresión binomial multivariada para establecer factores que predicen el número de errores intraoperatorios, reportes del cirujano sobre la dificultad del caso y los resultados clínicos e histopatológicos a corto plazo.Se identificaron un total de 1,331 errores intraoperatorios en 365 horas de cirugía (media de 18 por caso, IQR 16-22, rango 9-49). Ningún paciente, tumor o medición de pelvimetría pélvica, se correlacionó con la cuenta de errores pélvicos o totales, reporte del cirujano sobre dificultad del caso, carga cognitiva, datos operativos, calidad de la muestra, número o gravedad de eventos de morbilidad de 30 días y duración de la estadía (todos r <± 0.26, p > 0.05). El área mesorrectal se asoció con eventos adversos intraoperatorios importantes (OR, 1.09; IC 95%, 1.01-1.16; p = 0.015) y morbilidad postoperatoria (OR, 1.1; IC 95%, 1.01-1.2; p = 0.033). Como información subjetiva, hombres obesos fueron casos más difíciles (24 mm frente a 36 mm, p = 0.042) pero no se observaron efectos perjudiciales sobre el rendimiento o los resultados.Nuestro tamaño de muestra es un modesto riesgo de errores de tipo II y el sobreajuste de los modelos estadísticos.No se observa que las características anatómicas del paciente, tumor y pelvis ósea influyan en la dificultad operatoria de la escisión mesorrectal laparoscópica total. El área mesorrectal se identifica como un factor de riesgo para la morbilidad intraoperatoria y postoperatoria. Vea el resumen del video en http://links.lww.com/DCR/B35.

Non-Melanoma Skin Cancers in the Older Patient.

PURPOSE OF REVIEW: The incidence of non-melanomatous skin cancer (NMSC) increases with age and there are specific considerations regarding management of NMSC for the older patient population. Here we will review current data regarding treatment considerations and options for older patients with NMSC. RECENT FINDINGS: Hypofractionated regimens and high-dose brachytherapy may be non-surgical treatment options for older patients with NMSC. Other less aggressive strategies such as active surveillance can also be considered in some settings. Management of NMSC in the older patient population requires a thorough assessment of comorbidities, frailty, and life expectancy. Additionally, discussions regarding goals of care and quality of life (QOL) issues are especially important in this population. Older patients with NMSC in particular may benefit from a tailored treatment plan based on current available data rather than a broad application of general treatment guidelines for NMSC.

A Rare Case of Grey Zone Lymphoma Successfully Treated with Brentuximab Vedotin and R-CHP Chemotherapy.

INTRODUCTION: The diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin's lymphoma (cHL), also referred to as grey zone lymphoma (GZL), is a challenging diagnosis. There are no standardized guidelines; however, evidence strongly suggests that DLBCL-based regimens are effective in the treatment of GZL. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate that has established efficacy in relapsed/refractory Hodgkin and some T-cell lymphomas. There is some evidence that BV has a positive response in non-Hodgkin lymphoma (NHL) with a wide range of CD30 expressions-including GZL. CASE: We present a case of a patient initially diagnosed with cHL who underwent repeat biopsy which was revealed to be GZL. Based on PET scanning and immunohistochemical studies, she was classified as a stage IIIA CD20+/CD30+ GZL patient. Given her strong CD30 expression, she underwent 6 cycles of R-BV-CHP (rituximab, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone) chemotherapy and achieved complete response (CR) both clinically and radiographically. DISCUSSION: Given the rarity of GZL, this case illustrates the immense challenges in making the diagnosis, discusses the current treatment options, and suggests that BV may be a viable therapeutic candidate in the treatment of GZL.

Biomarkers for early detection of colorectal cancer and polyps: systematic review.

There is growing interest in early detection of colorectal cancer as current screening modalities lack compliance and specificity. This study systematically reviewed the literature to identify biomarkers for early detection of colorectal cancer and polyps. Literature searches were conducted for relevant papers since 2007. Human studies reporting on early detection of colorectal cancer and polyps using biomarkers were included. Methodologic quality was evaluated, and sensitivity, specificity, and the positive predictive value (PPV) were reported. The search strategy identified 3,348 abstracts. A total of 44 papers, examining 67 different tumor markers, were included. Overall sensitivities for colorectal cancer detection by fecal DNA markers ranged from 53% to 87%. Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection. Canine scent detection had a sensitivity of detecting colorectal cancer of 99% and specificity of 97%. The PPV of immunochemical fecal occult blood test (iFOBT) is 1.26%, compared with 0.31% for the current screening method of guaiac fecal occult blood test (gFOBT). A panel of serum protein biomarkers provides a sensitivity and specificity above 85% for all stages of colorectal cancer, and a PPV of 0.72%. Combinations of fecal and serum biomarkers produce higher sensitivities, specificities, and PPVs for early detection of colorectal cancer and adenomas. Further research is required to validate these biomarkers in a well-structured population-based study.

The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumor growth and survival via alphav integrin ligation.

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.

Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma.

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.