The diagnostic accuracy of local staging in colon cancer based on computed tomography (CT): evaluating the role of extramural venous invasion and tumour deposits.

PURPOSE: The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease). METHODS: All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard. RESULTS: A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits. CONCLUSION: The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study.

PURPOSE: Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome. METHODS: Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors. RESULTS: DTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45-2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02-4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR. CONCLUSIONS: Our data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.

An in vivo study of the primary and coupled rotations of the thoracic spine.

OBJECTIVE: To provide preliminary data on three-dimensional thoracic spine kinematics measured in vivo. DESIGN: This study measured the three planes of thoracic spine motion in normal subjects using an external measuring device. BACKGROUND: Few studies have investigated the primary and associated coupled rotations in the thoracic spine in vivo. Most knowledge of motion characteristics comes from in vitro studies which have limitations. There is a lack of agreement on the patterns of thoracic coupled motion especially that between lateral flexion and axial rotation. METHODS: Thoracic motion was examined in 60 normal subjects (30 males, 30 females) aged 18-24 years. The primary and coupled rotations of the thoracic regions T(1-4), T(4-8), T(8-12) were measured using a 3 SPACE Fastrak system. RESULTS: The three thoracic regions displayed the characteristic variations in range and distribution of primary rotations previously described. The pattern of coupled motion varied between subjects but an ipsilateral pattern predominated between lateral flexion and axial rotation in the middle and lower thoracic regions while the upper thoracic region was found to exhibit either a contralateral or ipsilateral pattern. Gender did not influence results. CONCLUSIONS: The pattern of coupled motion in the thoracic spine demonstrated some variability between subjects in vivo. Lateral flexion and axial rotation were strongly coupled with overall, their relationship being predominantly ipsilateral.

Identification and characterization of non-dividing cell populations in phase II cultures of human glial cells.

It has been reported that cultures of normal cells in phase II contain a non-multiplying cell population, the size of which increases with passage number. In phase II cultures of normal human glial cells we have found two subpopulations of non-proliferating cells, one of which has a characteristic morphology, and differs from the actively dividing cells in a number of respects: (1) they are larger although of various sizes and are well spread over a very large substratum area: (2) they contain a great number of granules showing acid phosphatase activity, being heavy metal positive and displaying the characteristic natural fluorescence of lipofuscin pigment; and (3) they frequently contained a central somewhat irregular nucleus with various numbers of darkly staining nucleolar-like structures. Cytophotometric nuclear DNA measurements of the described "large" cell population show a decreased proportion of diploid cells as compared to their smaller sister cells. Moreover, with increasing passage number, the DNA values for large cells shift towards higher ploidy levels resulting in a scattered aneuploid pattern in the oldest passage. This "large" cell subpopulation consists of between 2% and 3% of all passages and becomes greatly decreased following subcultivation. The other subpopulation of non-dividing cells is generally morphologically similar to the dividers, increases in size with passage number and is the more important in the phase III phenomenon.

Accuracy of cytologic diagnosis of central nervous system neoplasms in sterotactic biopsies.

The cytohistologic correlation is reported for 112 of the 128 consecutive sterotactic aspiration biopsies performed on patients with clinical and neuroradiologic evidence of brain tumors investigated at the Neurosurgery Department, Karolinska Hospital, from 1976 to 1979. The cytodiagnostic accuracy of benign and malignant tumors was 87% when adequate cell material was obtained. In 17 benign tumors of the sellar region, the diagnostic rate was 88%; cytologic examination independent of histologic biopsy is feasible in this area. The cytodiagnostic accuracy for 95 malignant central nervous system (CNS) tumors was 87% after adjusting for the appreciable sampling error inherent in the use of a stereotactic procedure during the early phase of the study. Two histopathologically proven infectious lesions were reported cytologically as benign. The main microscopic problems were the recognition of highly differentiated astroglial neoplasms and the differential diagnosis between poorly differentiated brain neoplasms and metastases to the CNS. Cytodiagnostic accuracy of CNS tumors can be increased by technical improvements in the stereotactic device, diagnostic experience and immunochemical staining.