Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma.

BACKGROUND AND AIMS: For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. METHODS: In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a "suspicious" nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. RESULTS: A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. CONCLUSIONS: Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.

18 F-FDG PET/MRI for restaging esophageal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose ( 18 F-FDG) PET/MRI may potentially improve tumor detection after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: This was a prospective, single-center feasibility study. At 6-12 weeks after nCRT, patients underwent standard 18 F-FDG PET/computed tomography (CT) followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18 F-FDG PET/CT or the 18 F-FDG PET/MRI first; the other scan was assessed 1 month later. Maximum standardized uptake value corrected for lean body mass (SUL max ) and mean apparent diffusion coefficient (ADC mean ) were measured at the primary tumor location. Histopathology of the surgical resection specimen served as the reference standard for diagnostic accuracy calculations. When patients had a clinically complete response and continued active surveillance, response evaluations until 9 months after nCRT served as a proxy for ypT and ypN (i.e. 'ycT' and 'ycN'). RESULTS: In the 21 included patients [median age 70 (IQR 62-75), 16 males], disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans) and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18 F-FDG PET/MRI vs. 18 F-FDG PET/CT was 38/57% vs. 76/61%. For ypN+, accuracy was 63/53% vs. 63/42%, resp. Neither SUL max (both scans) nor ADC mean were discriminatory for yp/ycT+ . Fourteen of 21 (67%) patients were willing to undergo a similar 18 F-FDG PET/MRI examination in the future. CONCLUSION: 18 F-FDG PET/MRI currently performs comparably to 18 F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience and performing serial scans might contribute to enhancing the accuracy of tumor detection after nCRT using 18 F-FDG PET/MRI. TRIAL REGISTRATION: Netherlands Trial Register NL9352.

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances.

INTRODUCTION: There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer "FAPI" has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells. METHODS: We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512). Patient-wise and lesion-wise comparisons were performed for primary tumour (T), lymph nodes (N), organ metastases (M) and peritoneal carcinomatosis (PC). Maximum standardized uptake values (SUVmax) and tumour-to-background ratios (TBR) were compared between PET using FAPI versus FDG (if reported). RESULTS: Ten articles met the inclusion criteria. In all studies, FAPI PET showed superiority over FDG-PET/CT/MRI for the detection of T, N, M and PC, both in the patient-wise and in lesion-wise comparisons (when performed). Additionally, higher SUVmax and TBRmax values were reported for use of FAPI compared to FDG. CONCLUSIONS: The positive results of this review warrant prospective clinical studies to investigate the accuracy and clinical value of FAPI PET for diagnosing and staging patients with pancreatic-, gastric- and cholangiocarcinoma.

Socioeconomic differences in participation and diagnostic yield within the Dutch national colorectal cancer screening programme with faecal immunochemical testing.

BACKGROUND: CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. METHODS: All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. RESULTS: Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72-0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69-0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16-1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). CONCLUSIONS: Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group.

Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study.

INTRODUCTION: Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. METHODS AND ANALYSIS: A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. ETHICS AND DISSEMINATION: The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. STUDY REGISTRATION: NL8231-10 December 2019; Netherlands Trial Register.

A multicentre retrospective analysis on growth of residual hepatocellular adenoma after resection.

BACKGROUND & AIMS: Hepatocellular adenoma (HCA) is a benign liver tumour that may require resection in select cases. The aim of this study was to the assess growth of residual HCA in the remnant liver and to advise on an evidence-based management strategy. METHOD: This multicentre retrospective cohort study included all patients with HCA who underwent surgery of HCA and had residual HCA in the remnant liver. Growth was defined as an increase of >20% in transverse diameter (RECIST criteria). Data on patient and HCA characteristics, diagnostic work-up, treatment and follow-up were documented and analysed. RESULTS: A total of 134 patients were included, one male. At diagnosis, median age was 38yrs (IQR 30.0-44.0) and median BMI was 29.9 kg/m2 (IQR 24.6-33.3). After resection, median number of residual sites of HCA was 3 (IQR 2-6). Follow-up of residual HCA showed regression in 24.6%, stable HCA in 61.9% and growth of at least one lesion in 11.2%. Three patients (2.2%) developed new HCA that were not visible on imaging prior to surgery. Four patients (3%, one male) underwent an intervention as growth was progressive. No statistically significant differences in clinical characteristics were found between patients with growing residual or new HCA versus those with stable or regressing residual HCA. CONCLUSION: In patients with multiple HCA who undergo resection, growth of residual HCA is not uncommon but interventions are rarely needed as most lesions stabilize and do not show progressive growth. Surveillance is indicated when residual HCA show growth after resection, enabling intervention in case of progressive growth.

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age.

BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 µg Hb/g feces) and high (47 µg Hb/g feces) cutoff value. RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the low cutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001). CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%.

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening.

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 µg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 µg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.

Quality Monitoring of a FIT-Based Colorectal Cancer Screening Program.

BACKGROUND: Quality assessment is crucial for consistent program performance of colorectal cancer (CRC) screening programs using fecal immunochemical test for hemoglobin (FIT). However, literature on the consistency of FIT performance in laboratory medicine was lacking. This study examined the consistency of FIT in testing positive or detecting advanced neoplasia (AN) for different specimen collection devices, lot reagents, and laboratories. METHODS: All participants with a FIT sample with a cutoff concentration of 47 µg Hb/g feces in the Dutch CRC screening program in 2014 and 2015 were included in the analyses. Multivariable logistic regression analyses were performed to estimate the odds ratios of collection devices, reagents, and laboratories on testing positive or detecting AN and positive predictive value (PPV). RESULTS: In total, 87519 (6.4%) of the 1371169 participants tested positive. Positivity rates and detection rates of AN differed between collection devices and reagents (all P < 0.01). In contrast, PPVs were not found to vary between collection devices, reagents, or laboratories (all P > 0.05). Positivity rates showed a small difference for laboratories (P = 0.004) but not for detection rates of AN. Size of the population affected by the deviating positivity rates was small (0.1% of the total tested population). CONCLUSIONS: Variations were observed in positivity and detection rates between collection devices and reagents, but there was no detected variation in PPV. Although the overall population effect of these variations on the screened population is expected to be modest, there is room for improvement.

Can point shear wave elastography differentiate focal nodular hyperplasia from hepatocellular adenoma.

PURPOSE: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are liver tumors that require different management. We assessed the potential of point shear wave elastography (pSWE) to differentiate FNH from HCA and the interobserver and intraobserver reliability of pSWE in the examination of these lesions and of native liver tissue (NLT). METHODS: The study included 88 patients (65 FNH, 23 HCA). pSWE was performed by two experienced liver sonographers (observers 1 [O1] and 2 [O2]) and acquired within the lesion of interest and NLT. Group differences, optimal cutoff for characterization and interobserver reliability was assessed with Mann-Whitney-U, area under the ROC curce (AUROC) and intraclass correlation coefficient (ICC). Intraobserver reliability in NLT was assessed in 20 healthy subjects using ICC. RESULTS: Median stiffness was significantly higher in FNH than in HCA (7.01 kPa vs 4.98 kPa for O1 (P = 0.017) and 7.68 kPa vs 6.00 kPa for O2 (P = 0.031)). A cutoff point for differentiation between the two entities could not be determined with an AUROC of 0.67 (O1) and 0.69 (O2). Interobserver reliability was good for lesion- stiffness (ICC = 0.86) and poor for NLT stiffness (ICC = 0.09). In healthy subjects, intraobserver reliability for NLT-stiffness was poor for O1 (ICC = 0.23) and moderate for O2 (ICC = 0.62). CONCLUSION: This study shows that pSWE cannot reliably differentiate FNH from HCA. Interobserver and intraobserver reliability for pSWE in NLT were insufficient. Interpretation of results gained with this method should be done with great caution.

Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI.

AIM: To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA). PATIENTS AND METHODS: Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2-9 HCA and at least 10 HCA. RESULTS: A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2-9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in patients with inflammatory HCA compared with steatotic HCA (31 vs. 26, respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%), whereas patients with inflammatory HCA were often diagnosed with multiple lesions (122/166, 73%). CONCLUSION: Our series show a significantly higher BMI and frequency of inflammatory HCA in patients with multiple HCA compared with single HCA.

Real-Time Monitoring of Results During First Year of Dutch Colorectal Cancer Screening Program and Optimization by Altering Fecal Immunochemical Test Cut-Off Levels.

BACKGROUND & AIMS: After careful pilot studies and planning, the national screening program for colorectal cancer (CRC), with biennial fecal immunochemical tests (FITs), was initiated in The Netherlands in 2014. A national information system for real-time monitoring was developed to allow for timely evaluation. Data were collected from the first year of this screening program to determine the importance of planning and monitoring for optimal screening program performance. METHODS: The national information system of the CRC screening program kept track of the number of invitations sent in 2014, FIT kits returned, and colonoscopies performed. Age-adjusted rates of participation, the number of positive test results, and positive predictive values (PPVs) for advanced neoplasia were determined weekly, quarterly, and yearly. RESULTS: In 2014, there were 741,914 persons invited for FIT; of these, 529,056 (71.3%; 95% CI, 71.2%-71.4%) participated. A few months into the program, real-time monitoring showed that rates of participation and positive test results (10.6%; 95% CI, 10.5%-10.8%) were higher than predicted and the PPV was lower (42.1%; 95% CI, 41.3%-42.9%) than predicted based on pilot studies. To reduce the burden of unnecessary colonoscopies and alleviate colonoscopy capacity, the cut-off level for a positive FIT result was increased from 15 to 47 µg Hb/g feces halfway through 2014. This adjustment decreased the percentage of positive test results to 6.7% (95% CI, 6.6%-6.8%) and increased the PPV to 49.1% (95% CI, 48.3%-49.9%). In total, the first year of the Dutch screening program resulted in the detection of 2483 cancers and 12,030 advanced adenomas. CONCLUSIONS: Close monitoring of the implementation of the Dutch national CRC screening program allowed for instant adjustment of the FIT cut-off levels to optimize program performance.

Burden of waiting for surveillance CT colonography in patients with screen-detected 6-9 mm polyps.

PURPOSE: We assessed the burden of waiting for surveillance CT colonography (CTC) performed in patients having 6-9 mm colorectal polyps on primary screening CTC. Additionally, we compared the burden of primary and surveillance CTC. MATERIALS AND METHODS: In an invitational population-based CTC screening trial, 101 persons were diagnosed with <3 polyps 6-9 mm, for which surveillance CTC after 3 years was advised. Validated questionnaires regarding expected and perceived burden (5-point Likert scales) were completed before and after index and surveillance CTC, also including items on burden of waiting for surveillance CTC. McNemar's test was used for comparison after dichotomization. RESULTS: Seventy-eight (77 %) of 101 invitees underwent surveillance CTC, of which 66 (85 %) completed the expected and 62 (79 %) the perceived burden questionnaire. The majority of participants (73 %) reported the experience of waiting for surveillance CTC as 'never' or 'only sometimes' burdensome. There was almost no difference in expected and perceived burden between surveillance and index CTC. Waiting for the results after the procedure was significantly more burdensome for surveillance CTC than for index CTC (23 vs. 8 %; p = 0.012). CONCLUSION: Waiting for surveillance CTC after primary CTC screening caused little or no burden for surveillance participants. In general, the burden of surveillance and index CTC were comparable. KEY POINTS: • Waiting for surveillance CTC within a CRC screening caused little burden • The vast majority never or only sometimes thought about their polyp(s) • In general, the burden of index and surveillance CTC were comparable • Awaiting results was more burdensome for surveillance than for index CTC.

Computer tomography colonography participation and yield in patients under surveillance for 6-9 mm polyps in a population-based screening trial.

PURPOSE: Surveillance CT colonography (CTC) is a viable option for 6-9 mm polyps at CTC screening for colorectal cancer. We established participation and diagnostic yield of surveillance and determined overall yield of CTC screening. MATERIAL AND METHODS: In an invitational CTC screening trial 82 of 982 participants harboured 6-9 mm polyps as the largest lesion(s) for which surveillance CTC was advised. Only participants with one or more lesion(s) ≥6 mm at surveillance CTC were offered colonoscopy (OC); 13 had undergone preliminary OC. The surveillance CTC yield was defined as the number of participants with advanced neoplasia in the 82 surveillance participants, and was added to the primary screening yield. RESULTS: Sixty-five of 82 participants were eligible for surveillance CTC of which 56 (86.2 %) participated. Advanced neoplasia was diagnosed in 15/56 participants (26.8 %) and 9/13 (69.2 %) with preliminary OC. Total surveillance yield was 24/82 (29.3 %). No carcinomas were detected. Adding surveillance results to initial screening CTC yield significantly increased the advanced neoplasia yield per 100 CTC participants (6.1 to 8.6; p < 0.001) and per 100 invitees (2.1 to 2.9; p < 0.001). CONCLUSION: Surveillance CTC for 6-9 mm polyps has a substantial yield of advanced adenomas and significantly increased the CTC yield in population screening. KEY POINTS: • The participation rate in surveillance CT colonography (CTC) is 86 %. • Advanced adenoma prevalence in a 6-9 mm CTC surveillance population is high. • Surveillance CTC significantly increases the yield of population screening by CTC. • Surveillance CTC for 6-9 mm polyps is a safe strategy. • Surveillance CTC is unlikely to yield new important extracolonic findings.

Evolution of Screen-Detected Small (6-9 mm) Polyps After a 3-Year Surveillance Interval: Assessment of Growth With CT Colonography Compared With Histopathology.

OBJECTIVES: Volumetric growth assessment has been proposed for predicting advanced histology at surveillance computed tomography (CT) colonography (CTC). We examined whether is it possible to predict which small (6-9 mm) polyps are likely to become advanced adenomas at surveillance by assessing volumetric growth. METHODS: In an invitational population-based CTC screening trial, 93 participants were diagnosed with one or two 6-9 mm polyps as the largest lesion(s). They were offered a 3-year surveillance CTC. Participants in whom surveillance CTC showed lesion(s) of ≥6 mm were offered colonoscopy. Volumetric measurements were performed on index and surveillance CTC, and polyps were classified into growth categories according to ±30% volumetric change (>30% growth as progression, 30% growth to 30% decrease as stable, and >30% decrease as regression). Polyp growth was related to histopathology. RESULTS: Between July 2012 and May 2014, 70 patients underwent surveillance CTC after a mean surveillance interval of 3.3 years (s.d. 0.3; range 3.0-4.6 years). In all, 33 (35%) of 95 polyps progressed, 36 (38%) remained stable, and 26 (27%) regressed, including an apparent resolution in 13 (14%) polyps. In 68 (83%) of the 82 polyps at surveillance, histopathology was obtained; 15 (47%) of 32 progressing polyps were advanced adenomas, 6 (21%) of 28 stable polyps, and none of the regressing polyps. CONCLUSIONS: The majority of 6-9 mm polyps will not progress to advanced neoplasia within 3 years. Those that do progress to advanced status can in particular be found among the lesions that increased in size on surveillance CTC.

Chronic lower urinary tract symptoms in women: classification of abnormalities and value of dedicated MRI for diagnosis.

OBJECTIVE: Chronic lower urinary tract symptoms are common in women. We present a classification of abnormalities that can be considered in the differential diagnosis for lower urinary tract symptoms and can show the value of dedicated state-of-the art MRI in the workup of patients. CONCLUSION: Dedicated MRI tailored to patient symptoms and clinical findings has the potential to map out morphologic causes and categorize dysfunctional conditions from those that are truly nonmorphologic.

Neoadjuvant chemotherapy followed by radiotherapy and concurrent hyperthermia in patients with advanced-stage cervical cancer: a retrospective study.

OBJECTIVE: To evaluate the efficacy of neoadjuvant chemotherapy, followed by radiotherapy and concurrent hyperthermia (triple therapy) in patients with advanced-stage cervical cancer. METHODS: We selected 43 patients from our hyperthermia database, who were treated from 1996 to 2010 with triple therapy for large primary tumours (>6 cm) or para-aortic lymph node metastases. All patients received platinum-based chemotherapy followed by full-dose radiotherapy, brachytherapy and five hyperthermia treatments. The response was evaluated by gynaecological examination and a CT-scan. Time-to-event variables were estimated using the Kaplan Meier method and the Cox regression method. RESULTS: The mean age of the patients was 50.4 years (range 29-80). The median tumour size was 5.6 cm at diagnosis (range 2.6-8.2), positive lymph nodes were present in 90.7%. A total of 67% of the patients completed all six planned courses of chemotherapy. After completion of neoadjuvant chemotherapy, 83.7% of patients achieved a complete or partial response. At the end of treatment, the complete response rate was 81.4% (95%CI 69.2-93.5). Grade 2, 3 and 4 acute vascular toxicity occurred in 17 patients. The incidence of grade 3-4 haematological toxicity did not exceed 10% and no neutropenic fever occurred. For grade 1-2 renal toxicity, a switch to carboplatin was made (n = 6). No acute grade 3-4 renal toxicity was observed. No treatment-related deaths were recorded. The median follow-up time was 29.8 months (range 4.1-124.8). Overall survival rate at 12 months was 79% (95%CI 57.4-92.3). CONCLUSION: The triple therapy seems feasible and effective in the treatment of advanced-stage, high-risk cervical cancer. However, chemotherapy-induced vascular toxicity occurred frequently, which may warrant the use of prophylactic anticoagulants. We recommend a phase II trial for prospective confirmation for comparison with standard chemoradiation and the use of anticoagulants.

Hepatocellular adenomas: correlation of MR imaging findings with pathologic subtype classification.

PURPOSE: To investigate the correlation between magnetic resonance (MR) imaging findings and pathologic subtype classification of hepatocellular adenoma (HCA). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. MR imaging studies of 61 lesions (48 patients; median age, 36 years) were available and were independently reviewed by two radiologists. Consensus readings on all morphologic and signal-intensity imaging features were obtained. Previously, these lesions had been classified on the basis of pathologic findings and immunohistochemical analysis. Fisher exact and χ² tests were performed to compare the results between the different subtypes. A Bonferroni correction was applied to correct for multiple testing (α < .0033). RESULTS: MR imaging signs of diffuse intratumoral fat deposition were present in seven (78%) of nine liver-fatty acid binding protein (L-FABP)-negative HCAs compared with five (17%) of 29 inflammatory HCAs (P = .001). Steatosis within the nontumoral liver was present in 11 (38%) of 29 inflammatory HCAs compared with none of the L-FABP-negative HCAs (P = .038). A characteristic atoll sign was only seen in the inflammatory group (P = .027). Presence of a typical vaguely defined type of scar was seen in five (71%) of seven ß-catenin-positive HCAs (P = .003). No specific MR imaging features were identified for the unclassified cases. CONCLUSION: L-FABP-negative, inflammatory, and ß-catenin-positive HCAs were related to MR imaging signs of diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defined scar, respectively. Since ß-catenin-positive HCAs are considered premalignant, closer follow-up with MR imaging or resection may be preferred.