Transient Changes in Serum CEA, CA19-9, CRP, YKL-40, and IL-6 during Adjuvant Chemotherapy and Survival of Patients with Colorectal Cancer.

Serum carcinoembryonic antigen (CEA) is frequently monitored to detect colorectal cancer (CRC) recurrence after surgery. The clinical significance of transiently increased CEA during adjuvant chemotherapy is poorly understood. Serum CEA, CA19-9, CRP, YKL-40, and IL-6 were measured before, during, and after adjuvant 5-fluorouracil-based chemotherapy in the randomised LIPSYT study population. The biomarker kinetic patterns were classified into three groups: no increase, a transient increase (≥10% increase followed by a decrease), and a persistent increase during the adjuvant treatment, and the associations of these patterns with disease free-survival (DFS) and overall survival (OS) were investigated by using Cox regression analyses. The findings were validated in two single-centre cohorts that received modern adjuvant chemotherapy. A transient increase in CEA occurred in about a half of the patients during chemotherapy, in all the cohorts. The patients with a transient increase had a roughly similar DFS and OS to the patients with no increase, and a more favourable survival compared to the patients with a persistent increase. In the LIPSYT cohort, the hazard ratio was 0.21 for DFS (CI95% 0.07-0.66) and 0.24 for OS (CI95% 0.08-0.76). Transient increases in CA19-9 and YKL-40 tended to be associated with a favourable survival. A transient increase in CEA during adjuvant chemotherapy is associated with a favourable survival when compared with a persistent increase.

Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer.

BACKGROUND: In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. MATERIAL AND METHODS: This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan-Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. RESULTS: Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI95% 3.85-13.58), impaired OS (HR 7.16; CI95% 3.76-13.63), and more relapses (HR 7.9; CI95% 3.4-18.2); but sensitivity for CEA in finding relapses was only 31% (CI95% 21-48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI95% 1.10-4.13], HR for CRP 3.14 [CI95% 1.21-8.16]), impaired DFS (HR 2.18 [CI95% 1.12-4.24] or 3.23 [CI95% 1.34-7.82]), and impaired OS (2.33 [CI95%1.24-4.40] or 2.68 [CI95%1.12-6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. CONCLUSION: In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.

Can carcinoembryonic antigen replace computed tomography in response evaluation of metastatic colorectal cancer?

INTRODUCTION: Response Evaluation Criteria in Solid Tumours (RECISTs 1.1) define computed tomography (CT) as the gold standard in response evaluation of patients with metastatic colorectal cancer (mCRC) who are undergoing chemotherapy. The aim of this study was to evaluate whether carcinoembryonic antigen (CEA), which is cheaper and easier to perform, can replace repeated CT. MATERIAL AND METHODS: The study included 66 patients with non-resectable mCRC participating in a phase I-II study. CEA values were determined, and CT images were taken every 2 months. CT images were externally and retrospectively reviewed according to the RECIST 1.1 criteria. Different cut-off values for CEA change in percent (DeltaCEA%) compared with baseline or nadir value underwent testing to find patients with disease control (that is stable disease, partial or complete response) at 2, 4, 6 and 8 months, in order to identify those who could have continued with chemotherapy based on CEA values alone. CT verification is needed in progressive disease (PD), and therefore identifying PD patients was our secondary endpoint. RESULTS: The results showed that by using a cut-off value of 0 for DeltaCEA%, disease control was seen in all patients at all measuring points (negative predictive value (NPV) = 1.0). Secondarily, increasing CEA was able to identify all PD patients (sensitivity (Se) = 1.0) and in 50-74% of the patients increasing CEA provided a lead time to PD on upcoming CT. It was possible to replace CT with CEA in all patients with decreasing CEA, meaning that 23-47% of CT scans could have been avoided at any given time point. CONCLUSION: When the CEA level at a certain measuring point is the same or lower than CEA at baseline or at nadir (the measuring point with the lowest CEA value) during treatment, CEA can replace CT.

Pilonidal disease treatment by radial laser surgery (FiLaC™): The first Finnish experience.

BACKGROUND AND OBJECTIVE: Pilonidal disease is common, and it afflicts especially young adults, causing disability. Several types of treatment methods are applicable, but no consensus exists regarding the best method. The aim of our study was to assess the novel radial laser probe treatment in pilonidal disease and report the success rate and recurrence rate. METHODS: We studied retrospectively 86 patients who, according to our hospital patient records, underwent radial laser probe surgery between January 2017 and September 2019. RESULTS: In a mean follow-up time of 14 months, the success rate at 2 months was 86%. Most operations were done under local anesthesia on a day-surgery basis. The recovery time was rapid, and median sick leave was 12 days. Of those initially successfully treated, 3% developed a recurrence. Altogether 17% of the patients underwent a re-operation. Spillage of pus during surgery, however, reduced the success rate to 53%. CONCLUSIONS: Radial laser probe treatment is a quick, safe, and minimally invasive treatment choice for pilonidal disease, especially when no active infection is present.

Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation.

BACKGROUND: Acute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules. METHODS: Kidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous-arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage. RESULTS: Significant renal release of LFABP [trans-renal gradient 8.4 (1.7-30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1-5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood. CONCLUSIONS: Ischaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.

Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer.

In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.

CEA fluctuation during a single fluorouracil-based chemotherapy cycle for metastatic colorectal cancer.

BACKGROUND: Carcinoembryogenic antigen (CEA) is useful in the evaluation of chemotherapy response of metastatic colorectal cancer (CRC). We studied weekly CEA during one fluorouracil-based chemotherapy cycle, correlated with long-term (8-12 week interval) computed tomography (CT) and CEA responses. PATIENTS AND METHODS: CEA, liver function tests and inflammatory parameters were measured prospectively at baseline, day 7, day 14, and after the cycle (day 21/28), in 60 patients with metastatic CRC. RESULTS: CEA non-significantly decreased at day 7 and was increased on day 14. In progressive disease, CEA increased significantly during the evaluation cycle (55.4 µg/l vs. 148.2 µg/l; p=0.024), but the level was stable in patients with disease control (10.6 µg/l vs. 17.8 µg/l; p=0.58). CEA fluctuation correlated neither with liver function test nor with inflammatory parameters. Correlation of long-term response was most evident in progressive disease. CONCLUSION: CEA should not be measured during 5-fluorouracil-based oral chemotherapy nor within two weeks from intravenous chemotherapy administration.