The Ratio of Free Fatty Acids (Ffas) Divided By High-Density Lipoprotein Cholesterol (HDL-C) Is A Promising Pre-Treatment Biomarker For Predicting Worse Overall Survival (OS) of Neuroendocrine Tumours (Nets) In The Colorectum: A Retrospective Study.

Background: free fatty acids (FFAs) and high-density lipoprotein cholesterol (HDL-C) were associated with various malignancy. However, whether FFA, HDL-C and FFA/HDL-C can play a potiential role in predicting patients with colorectal neuroendocrine tumours (NETs) was unclear. Meanwhile, FFA/HDL-C has a superior prognosis ability was unknown, too.Methods: One hundred patients with pathologically diagnosed colorectal NETs in 2011-2017 were enrolled, and the levels of FFA, HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), cholesterol (CHOL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) between colorectal NET patients and healthy controls matched by age and sex were compared. In addition, the association of clinicopathological characteristics and follow-up data with FFA, HDL-C and FFA/HDL-C was analysed.Results: FFA was overexpressed (0.55±0.23 vs. 0.48±0.11, P= 0.006), and HDL-C was underexpressed (1.31±0.41 vs. 1.41±0.29, P=0.046) in colorectal NETs. FFA ≥0.52 mmol/L predicted lymph node metastasis (LNM) (P=0.015), HDL-C ≤1.0 mmol/L predicted tumour size ≥2 cm (P=0.017), and FFA/HDL-C>0.75 predicted tumour grade (P=0.030), LNM (P=0.014), and tumour size(P=0.018). No significant association was found between FFA and tumour grade (P=0.613) or HDL-C and tumour grade (P=0.594) or FFA and tumour size (P=0.142) or HDL-C and LNM (P=0.443). FFA ≥0.52 mmol/L (P=0.014) and HDL-C ≤1.0 mmol/L predicted worse overall survival (OS) (P=0.019). FFA/HDL-C predicted an even worse prognosis in terms of OS (P<0.001).Conclusion: FFA ≥0.52 mmol/L HDL-C ≤1.0 mmol/L and FFA/HDL-C>0.75 were promising cut-off values in predicting LNM, tumour size and worse OS in colorectal NETs.

Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group – ESOI Joint Paper

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.

Risk factors for lymph node metastasis and prognosis in colorectal neuroendocrine tumours

Purpose The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. Methods The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. Results A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. Conclusions When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.

Primary non-Hodgkin’s lymphoma of the orbit: treatment outcomes from India

Background: Primary non-Hodgkin’s lymphoma (NHL) of the orbit is rare. Orbital NHLs show good response to both radiotherapy (RT) and chemotherapy, and hence, the emphasis should be to ensure maximum cure rate with minimum morbidity. In this study, we present the clinical profile and treatment outcomes of patients with NHL who had initial presentation in the orbit. Materials and methods: In this retrospective analysis, case records of patients with a diagnosis of NHL of the orbit were analysed from January 2005 to January 2015. Patients were worked up and staged according to the Ann Arbor system. Patients with large tumours were initially given chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin and prednisolone) three weekly for 4–6 cycles. Patients with residual disease were given RT 20–30 Gy at 2 Gy per fraction. RT when given as a primary treatment consisted of 36–45 Gy at 1·8–2 Gy per fraction on either Cobalt 60 machine or linear accelerator. Results: A total of 52 patients with diagnosis of orbital NHL were included in this study. Median age at presentation was 57 years (range 13–71). Left, right and bilateral orbit was involved in 21 (40%), 28(54%) and 3(6%) patients, respectively. Low- and high-grade pathology was seen in 39(75%) and 13(25%) patients, respectively. On immunohistochemistry, 23(44%) tumors were CD 20 positive. After staging, 33 (63%) patients had stage I disease. Median tumour size was 4·0 × 3·2 × 1·5 cm (1·7 × 1·7 × 1·4 cm to 5·8 × 4·0 × 4·7 cm). Primary RT was given to 7(13%) patients. Upfront chemotherapy was given in 45(86·5%) patients, out of which 24 had stage I disease. RT consolidation was done in 26 (50%) patients for residual disease after chemotherapy. Median follow-up was 88 months (range 29–183 months). Relapse occurred in 6(9·6%) patients; 2 local; 2 local + distant and in 2 distant alone. These patients were successfully salvaged with systemic chemotherapy and local RT. One patient died due to neutropenia. Overall survival in this series was 96%. Conclusions: Excellent local control was achieved with initial chemotherapy followed by RT for primary orbital NHL with minimal toxicity. We recommend a dose of 36–40 Gy for definitive RT and 30 Gy for lymphoma following chemotherapy using 2 Gy/fraction for Indian patients who present with bulky tumours. RT should be incorporated in treatment of orbital NHL whenever possible as it is safe, effective and is associated with minimal complications.

RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance

Background Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women. Material and methods This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays. Results About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance. Conclusion RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target.

LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b

Background Although long noncoding RNA HLA complex group 18 (lncRNA HCG18) has been suggested to regulate cell growth in several tumours, the function of HCG18 in epithelial ovarian cancer (EOC) and its mechanism are still unclear. Methods shRNAs were applied to reduce HCG18 and related genes. For overexpression of miRNA, a miRNA mimic was transfected into cells. Quantitative real-time PCR (qRT–PCR) was used to detect levels of HCG18, miR-29a/b, and mRNAs. MTT, colony formation, wound healing and Transwell assays were used to evaluate cell proliferation, migration and invasion, respectively. A luciferase reporter assay was utilized to evaluate NF-κB activity and the binding of miRNAs with HCG18 or TRAF4/5. BALB nude mice injected with cells stably expressing shHCG18 or shNC were used for in vivo modelling. Subcutaneous tumour growth was monitored in nude mice, and immunohistochemistry (IHC) was used to determine expression of the proliferation marker Ki67. Results Abnormal expression of HCG18 and miR-29a/b was observed in EOC tissues. Knockdown of HCG18 using shRNA inhibited proliferation, migration, EMT and the proinflammatory pathway in EOC cells. miR-29a/b mimics and TRAF4/5 knockdown exhibited effects similar to HCG18 knockdown. Further experiments suggested that HCG18 directly targets miR-29a/b and upregulates TRAF4/5 expression, which are inhibited by targeting miR-29a/b. Moreover, overexpression of TRAF4/5 antagonized the inhibitory effect of HCG18 knockdown, suggesting that they are involved in HCG18-mediated oncogenic effects. Silencing HCG18 reduced tumour size and levels of Ki67 and TRAF4/5 while increasing miR-29a/b levels in vivo. Conclusions Taken together, our data revealed an oncogenic signalling pathway mediated by HCG18 in ovarian cell lines, which functions as a ceRNA of miR-29a/b and thus derepresses expression levels of TRAF4/5, facilitating NF-κB pathway-mediated promotion of EOC cell proliferation and migration.

Does the modified Glasgow Prognostic Score aid in the management of patients undergoing surgery for a soft-tissue sarcoma?

Aims The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. Methods This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. Results We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. Conclusion This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168–176.

Estimation of Clinical Size of Breast Tumour Lesions Using Contrast Enhanced Magnetic Resonance Imaging: Delineation of Tumour Boundaries

This study covers an extended spectrum of clinical cases (1) to analyze the accurate tumour size, (2) to demarcate accurate tumour boundaries in order to plan an effective target volumes for radiotherapy, thermal ablation including radiofrequency ablation and nanoparticles induced thermal ablation. Once the clinical size of the tumour is established, realistic three-dimensional volume of the tumour can be calculated. Accurate margins (0.5 cm -1 cm) can only be sacrificed if true tumour boundaries with irregular nodal spread can be retrieved.

Open Partial Nephrectomy with Zero Ischaemia Using a Supra 12th Rib Miniflank Incision: A Minimally Invasive Open Approach for Small Renal Masses

Introduction. To assess a minimally invasive open technique for partial nephrectomy with zero ischaemia time. Methods. A review was performed in a prospectively maintained database of a single surgeon series of all patients undergoing partial nephrectomy using a supra 12th rib miniflank incision with zero ischaemia. Data of seventy one patients who underwent a partial nephrectomy over an 82-month period were analyzed. Data analyzed included operative time, estimated blood loss, pre and postoperative renal function, complications, final pathological characteristics, and tumour size. Results. Seventy one partial nephrectomies were performed from February 2009 to October 2015. None were converted to radical nephrectomy. Mean operative time was 72 minutes (range 30–250), and mean estimated blood loss was 608 mls (range 100–2500) with one patient receiving blood transfusion. The mean pre and postoperative haemoglobin levels were 144 and 112 g/l. The mean pre and postoperative creatinine levels were 82 and 103 Umol/L. There were 8 Clavian–Dindo Grade 2 complications and 1 major complication (Clavian IIIa). Histology confirmed 24 benign lesions and 47 malignant lesions, 46 cT1a lesions, 24 cT1b lesions, and 1 cT2 lesion. Median follow-up was 38 months with no local recurrence or progression of disease with 5 patients having a positive margin (7%). Conclusion. Our results demonstrate that a supra 12th miniflank incision open partial nephrectomy with zero ischaemic time for SRMs has satisfactory outcomes with preservation of renal function. A minimally invasive open partial nephrectomy remains an important option for units that cannot offer patients a laparoscopic or a robotic procedure.

De-Escalating Breast Cancer Surgery: Should We Apply Quality Indicators from Other Jurisdictions in Canada?

Quality Indicators (QIs), including the breast-conserving surgery (BCS) rate, were published by the European and American Breast Cancer Societies and this study assesses these in a Canadian population to look for opportunities to de-escalate surgery. A total of 2311 patients having surgery for unilateral, unifocal breast cancer between 2013 and 2017 were identified and BCS QIs calculated. Reasons for mastectomy had been prospectively collected with synoptic operative reporting. Our BCS rate for invasive cancer < 3 cm was 77.1%, invasive cancer < 2 cm was 84.1%, and DCIS < 2 cm was 84.9%. There was no statistically significant change in BCS rates over a five-year period, but there was a reduction in contralateral prophylactic mastectomies (CPM) from 28% in 2013 to 16% in 2017 (p < 0.001). Trend analysis looking at tumour size and medical need for mastectomy indicated that 80% of patients at our centre would be eligible for BCS with tumour cut off of 2.5 cm. Our institution met American but not European QI standards for BCS rates, potentially indicating a difference in patient demographics compared to Europe. Our results support the understanding that BCS rates are influenced by multiple factors and are challenging to compare across jurisdictions. CPM rates may offer a more actionable opportunity to de-escalate surgery for breast cancer.