Postpartum ovarian vein thrombosis with left renal venous infarction after vaginal delivery.

A primipara in her late 20s presented with abdominal pain and pain in the left flank 14 days after a ventouse delivery. She was treated with antibiotics, antiemetics and analgesics with the initial differential diagnosis of cystitis, pyelonephritis or nephrolithiasis. Despite the treatment, the patient experienced increased colic pain and nausea. An ultrasound showed an enlarged left kidney, suggesting pyelonephritis, and thereby, the antibiotic treatment was adjusted accordingly. Despite additional pain medication, pain relief could not be achieved. The diagnosis of ovarian venous thrombosis was considered, and an abdominal CT scan confirmed the diagnosis. The patient was treated with anticoagulant therapy. Hypercoagulability work-up revealed a heterozygous mutation of the Factor V Leiden. Our patient awaits a haematologic follow-up.

Paraneoplastic anti-TIF1-gamma-positive dermatomyositis as expression of cervical squamous cell carcinoma recurrence.

Idiopathic inflammatory myopathies are neuromuscular disorders characterised by muscle weakness and histologically inflammation within the muscle. Dermatomyositis and polymyositis are highly associated with a wide range of cancers, especially in antitranscriptional intermediary factor-1 (TIF1)-gamma-positive myositis. We present a case of paraneoplastic dermatomyositis in a patient with a medical history of a FIGO stage 1B1 cervical squamous cell carcinoma. Anti-TIF1-gamma autoantibodies were detected by myositis lineblot analysis and a PET-CT scan revealed an abnormality positioned at the right ovary. She underwent laparoscopic exploration and pathological analysis of the PET-positive abnormality showed a lymphogenic metastasis of a squamous cell carcinoma, competitive with cervical carcinoma recurrence. She started chemoradiation as curative oncological treatment. The dermatomyositis was successfully treated with high-dose corticosteroids. Physicians should be aware of the association between myositis and the increased risk of malignancies.

Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

BACKGROUND: In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC. METHODS: A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia - haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis - platelets >400 × 109 platelets/L, leucocytosis - leukocytes >10 × 109/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy. RESULTS: A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively, P = 0.002 and P = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19-4.50), P = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy (n = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival (P = 0.005 and P = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy (n = 74), anaemia was associated with reduced disease-specific survival (P = 0.041). CONCLUSIONS: Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy.What is already known on this subject? In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome.What do the results of this study add? It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients.What are the implications of these findings for clinical practice and/or further research? Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

In this study we focused on three specific blood values before surgery to predict survival outcomes in endometrial cancer patients: low haemoglobin (anaemia), high platelet count (thrombocytosis) and high white blood cell count (leucocytosis). We studied 894 patients with endometrial cancer over about 4.5 years, in which 11.5% had anaemia, 8.8% thrombocytosis and 12.7% leucocytosis. Anaemia was linked to a lower chance of surviving endometrial cancer, even after we considering patients' age, thrombocytosis, leucocytosis and the endometrial cancer risk classification groups. In patients who received radiotherapy after surgery (293 patients), anaemia was linked to a lower change of surviving and cancer coming back within 5 years. In patients within the intermediate endometrial cancer risk classification group who only received specific radiotherapy (74 patients), anaemia was even linked with lower chance of survival. In conclusion, anaemia is an important factor in predicting endometrial cancer outcomes, and it might also make radiotherapy less effective for some patients.

Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer.

Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific-(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC.

Comparing Methods to Determine Complete Response to Chemoradiation in Patients with Locally Advanced Cervical Cancer.

OBJECTIVES: There is no consensus on the most reliable procedure to determine remission of cervical cancer after chemoradiotherapy (CRT). Therefore, this study aims to assess the diagnostic performance of two different imaging techniques, MRI and 18F[FDG]-PET/CT, in determining the presence of locoregional residual disease after CRT in patients with locally advanced cervical cancer. METHODS: Patients diagnosed with locally advanced cervical cancer (FIGO 2009) treated with CRT were retrospectively identified from a regional cohort. The accuracy of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was assessed with histology as the reference standard. RESULTS: The negative predictive value (NPV) and positive predictive value (PPV) for locoregional residual disease detection of MRI and 18F[FDG]-PET/CT combined were 84.2% (95% CI 73.2-92.1), and 70.4% (95% CI 51.8-85.2), respectively. The NPV and PPV of MRI alone were 80.2% (95% CI 71.2-87.5) and 47.7% (95% CI 35.8-59.7), respectively, and values of 81.1% (95% CI 72.2-88.3) and 55.8 (95% CI 42.2-68.7), respectively, were obtained for 18F[FDG]-PET/CT alone. CONCLUSION: In this study, the reliability of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was limited. Combining MRI and 18F[FDG]-PET/CT did not improve predictive values. Routine use of both MRI and 18F[FDG]-PET/CT in the follow-up after CRT should be avoided. MRI during follow-up is the advised imaging technique. Pathology confirmation of the presence of locoregional residual disease before performing salvage surgery is warranted.

Improving preoperative diagnosis in endometrial cancer using systematic morphological assessment and a small immunohistochemical panel.

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2 ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC = 0.92; 95%CI = 0.88-0.95) compared to solely morphological evaluation (AUC = 0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC = 0.93; 95%CI = 0.88-0.98) compared to solely morphological evaluation (AUC = 0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2 ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%).

Extrauterine adenomyoma located in the inguinal region: a case report of a 44-year-old woman.

Adenomyomas are benign tumours made of smooth muscle cells, endometrial glands and stroma. An extrauterine location is extremely rare with an unknown pathogenesis. Preoperative diagnosis is challenging and pathologic examination is necessary to confirm the diagnosis. Here we present a case report of a 44-year-old woman with a painful non-reducible mass in the right inguinal region without fever or other alarming symptoms 2 months after a laparoscopic hysterectomy. She was treated with a surgical resection of the mass. Extrauterine adenomyoma is a very uncommon entity. Preoperative workup is challenging, as confirmation of the diagnosis can only be achieved by histopathological analysis following surgical excision.

Polymorphisms in MMP-14 and MMP-2 genes and ovarian cancer survival.

BACKGROUND: Functional polymorphisms in matrix metalloproteinases can increase or decrease the risk of cancer. This study focused on ovarian cancer and investigated how polymorphisms in the coding region of MMP-14 and the promoter region of MMP-2 are related to clinical characteristics including survival. METHODS: In 144 patients with ovarian tumours from a Caucasian population, polymorphisms of MMP-14 (+7096 and +6767) and MMP-2 (-735 and -1306) were analysed. These results were then correlated to the immunohistochemical expression of MMP-14 and MMP-2 and clinical characteristics. RESULTS: In these patients, the MMP-14 +7096 polymorphism showed only TT genotype, in sharp contrast to the described MAF (minimal allele frequency) C of 27%. The MMP-14 +6767 G>A polymorphism was found to have a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046) for recurrence-free survival in advanced-stage patients. However, this significance disappeared after Bonferroni correction for multiple testing. No other correlations between MMP-14 and MMP-2 polymorphisms, immunohistochemistry and clinical characteristics were found, except between the MMP-2 -1306 polymorphism and differentiation grade, with a Spearman correlation coefficient of -0.19, p 0.064. CONCLUSIONS: In ovarian cancer, the MMP-14 +6767 G>A polymorphism in the coding region seems to improve recurrence-free survival with a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046). However, as this significance disappeared after correction for multiple testing, there is a need for further research on the functional effect of this change in the MMP-14 gene with larger patient sample sizes.

Improved preoperative risk stratification with CA-125 in low-grade endometrial cancer: a multicenter prospective cohort study.

OBJECTIVES: The global obesity epidemic has great impact on the prevalence of low-grade endometrial carcinoma. The preoperative tumor serum marker cancer antigen 125 (CA-125) might contribute to improved identification of high-risk patients within this group. The study aimed to investigate the prognostic value of CA-125 in relation to established preoperative prognosticators, with a focus on identifying patients with poor outcome in low-grade endometrial carcinoma (EC) patients. METHODS: Prospective multicenter cohort study including all consecutive patients surgically treated for endometrial carcinoma in nine collaborating hospitals from September 2011 until December 2013. All preoperative histopathological diagnoses were reviewed in a blinded manner. Associations between CA-125 and clinicopathological features were determined. Univariable and multivariable analysis by Cox regression were used. Separate analyses were performed for preoperatively designated low-grade and high-grade endometrial carcinoma patients. RESULTS: A total of 333 patients were analyzed. CA-125 was associated with poor prognostic features including advanced International Federation of Gynecology and Obstetrics (FIGO) stage. In multivariable analysis, age, preoperative tumor and CA-125 were significantly associated with disease-free survival (DFS); preoperative grade, tumor type, FIGO and CA-125 were significantly associated with disease-specific survival (DSS). Low-grade EC patients with elevated CA-125 revealed a DFS of 80.6% and DSS of 87.1%, compared to 92.1% and 97.2% in low-grade EC patients with normal CA-125. CONCLUSION: Preoperative elevated CA-125 was associated with poor prognostic features and independently associated with DFS and DSS. Particularly patients with low-grade EC and elevated CA-125 represent a group with poor outcome and should be considered as high-risk endometrial carcinoma.

Posterior axilla sling traction: a new technique for severe shoulder dystocia.

We describe a case of severe shoulder dystocia where, after failing of the known techniques, the posterior axilla sling traction technique was applied successfully. This technique was first described in 2009 by Hofmeyr and Cluver and must be considered at severe cases of shoulder dystocia where all other non-invasive techniques have failed.

Implementation of laparoscopic hysterectomy for endometrial cancer over the past decade.

BACKGROUND: Laparoscopic hysterectomy (LH) for the treatment of early-stage endometrial carcinoma/cancer (EC) has demonstrated to be safe in several randomized controlled trials. Yet, data on implementation of LH in clinical practice are limited. In the present study, implementation of LH for EC was evaluated in a large oncology network in the Netherlands. RESULTS: Retrospectively, a total of 556 EC patients with FIGO stage I-II were registered in the selected years. The proportion of LH gradually increased from 11% in 2006 to 85% in 2015. LH was more often performed in patients with low-grade EC and was not related to the studied patient characteristics. The introduction of TLH was frequently preceded by LAVH. Patients treated in teaching hospitals were more likely to undergo a LH compared to patients in non-teaching hospitals. The conversion rate was 7.7%, and the overall complication rates between LH and AH were comparable, but less postoperative complications in LH. CONCLUSIONS: Implementation of laparoscopic hysterectomy for early-stage EC increased from 11 to 85% in 10 years. Implementation of TLH was often preceded by LAVH and was faster in teaching hospitals.

Mesenteric lymphangioma mimicking a cystic ovarian mass on imaging.

Pelvic cystic masses are frequently observed in women. Most lesions are benign and of ovarian origin. However, non-ovarian lesions can be easily confused with cystic ovarian masses on imaging, which hampers diagnostic and therapeutic management. In this report, a rare case of mesenteric lymphangioma mimicking an ovarian cystic mass, discovered as an incidental finding on orthopaedic MRI in an adult female, is presented. The report highlights the sometimes difficult diagnostic process of pelvic cystic masses, due to an extensive differential diagnosis and the fact that imaging is often inconclusive. Even though most cystic masses are of ovarian origin, non-ovarian causes can mimic ovarian masses and should be considered as differential diagnoses. Surgical exploration may be necessary to exclude malignant causes.

[A woman with a special cervix]. / Een vrouw met een bijzondere cervix.

A 40-year-old woman (nulligravida) presented with abnormal cervical cytology. At colposcopy a double external uterine os was discovered with a levonorgestrel intra uterine contraceptive device placed in the opening on the left side. Ultrasound revealed an uterus bicornis bicollis. Despite frequent examinations, the abnormality had not been discovered earlier. Therefore, contraception and cervical cytology sampling had most likely been inadequate.

Labor dystocia as first presentation of pelvic malignancy.

The underlying causes of labor dystocia can be various. Lack of expulsive forces or fetal malpresentation are amongst the most common ones. However, pelvic masses are described as well. Here we describe two cases of labor dystocia as first presentation of pelvic malignancy.

Detection and genotyping of human papillomavirus in self-obtained cervicovaginal samples by using the FTA cartridge: new possibilities for cervical cancer screening.

This study assesses human papillomavirus (HPV) detection and genotyping in self-sampled genital smears applied to an indicating FTA elute cartridge (FTA cartridge). The study group consisted of 96 women, divided into two sample sets. All samples were analyzed by the HPV SPF(10)-Line Blot 25. Set 1 consisted of 45 women attending the gynecologist; all obtained a self-sampled cervicovaginal smear, which was applied to an FTA cartridge. HPV results were compared to a cervical smear (liquid based) taken by a trained physician. Set 2 consisted of 51 women who obtained a self-sampled cervicovaginal smear at home, which was applied to an FTA cartridge and to a liquid-based medium. DNA was obtained from the FTA cartridges by simple elution as well as extraction. Of all self-obtained samples of set 1, 62.2% tested HPV positive. The overall agreement between self- and physician-obtained samples was 93.3%, in favor of the self-obtained samples. In sample set 2, 25.5% tested HPV positive. The overall agreement for high-risk HPV presence between the FTA cartridge and liquid-based medium and between DNA elution and extraction was 100%. This study shows that HPV detection and genotyping in self-obtained cervicovaginal samples applied to an FTA cartridge is highly reliable. It shows a high level of overall agreement with HPV detection and genotyping in physician-obtained cervical smears and liquid-based self-samples. DNA can be obtained by simple elution and is therefore easy, cheap, and fast. Furthermore, the FTA cartridge is a convenient medium for collection and safe transport at ambient temperatures. Therefore, this method may contribute to a new way of cervical cancer screening.

Parental acceptance of Human Papillomavirus vaccines.

OBJECTIVE: To determine whether parents would accept Human Papillomavirus (HPV) vaccination for their children and which variables may influence their decision, including knowledge about cervical cancer and HPV. STUDY DESIGN: Three hundred and fifty-six parents of children aged 10-12 years were interviewed regarding the acceptance of an HPV vaccine for their children and their knowledge of HPV and cervical cancer. All data were recorded anonymously. Results were compared using the chi(2)- and the Mann-Whitney test. RESULTS: HPV vaccination would be accepted by 88% of the parents, preferably when the child is aged 10-12 years. Parents of children who received all the vaccinations of the National Vaccination Programme accepted HPV vaccination significantly more. Less than a third of all parents had heard of HPV, and 14% were aware of the causal relationship of HPV and cervical cancer. Knowledge of HPV and cervical cancer, religion, age, education, and marital status did not show any significant relation with HPV vaccine acceptance. CONCLUSIONS: A majority of the parents would accept HPV vaccination. HPV vaccine acceptance seems to be dependent on vaccine acceptance in general, even more than on knowledge of HPV and its causal relation with cervical cancer. However, parents requested more information about cervical cancer, HPV, and HPV vaccination, before the HPV vaccine is introduced.

High-risk HPV presence in cervical specimens after a large loop excision of the cervical transformation zone: significance of newly detected hr-HPV genotypes.

Large loop excision of the cervical transformation zone (LLETZ) is a well-established treatment for high-grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high-risk (hr-) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr-HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr-HPV in 85 high-grade squamous cervical LLETZ biopsies and in the first follow-up smear was determined. In 80 (94%) of the LLETZ biopsies hr-HPV was detected in contrast to 30 (35%) hr-HPV positive follow-up scrapes. Twenty of the 80 hr-HPV positive women (25%) had the same hr-HPV genotypes in their follow-up cervical smears as was found in the corresponding biopsies. In the follow-up smear of 13 women a new hr-HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re-activation of this virus from proximal layers of the cervical canal incised during surgery.

Evaluation of the SPF10-INNO LiPA human papillomavirus (HPV) genotyping test and the roche linear array HPV genotyping test.

The need for accurate genotyping of human papillomavirus (HPV) infections is becoming increasingly important, since (i) the oncogenic potential among the high-risk HPV genotypes varies in the pathogenesis of cervical cancer, (ii) monitoring multivalent HPV vaccines is essential to investigate the efficiency of the vaccines, and (iii) genotyping is crucial in epidemiologic studies evaluating HPV infections worldwide. Various genotyping assays have been developed to meet this demand. Comparison of different studies that use various HPV genotyping tests is possible only after a performance assessment of the different assays. In the present study, the SPF(10) LiPA version 1 and the recently launched Roche Linear Array HPV genotyping assays are compared. A total of 573 liquid-based cytology samples were tested for the presence of HPV by a DNA enzyme immunoassay; 210 were found to be positive for HPV DNA and were evaluated using both genotyping assays (163 with normal cytology, 22 with atypical squamous cells of undetermined significance, 20 with mild/moderate dysplasia, and 5 with severe dysplasia). Comparison analysis was limited to the HPV genotype probes common to both assays. Of the 160 samples used for comparison analysis, 129 (80.6%) showed absolute agreement between the assays (concordant), 18 (11.2%) showed correspondence for some but not all genotypes detected on both strips (compatible), and the remaining 13 (8.2%) samples did not show any similarity between the tests (discordant). The overall intertest comparison agreement for all individually detectable genotypes was considered very good (kappa value, 0.79). The genotyping assays were therefore highly comparable and reproducible.

Reduction in muscle glycogen and protein utilization with glucose feeding during exercise.

Effects of feeding glucose on substrate metabolism during cycling were studied. Trained (60.0 +/- 1.9 mL x kg(-1) x min(-1)) males (N = 5) completed two 75 min, 80% VO(2max) trials: 125 g 13(C)-glucose CHO); 13(C)-glucose tracer, 10 g (C). During warm-up (30 min 30% VO2max) 2 . 2 g 13(C)-glucose was given as bicarbonate pool primer. Breath samples and blood glucose were analyzed for 13(C/12)C with IRMS. Protein oxidation was estimated from urine and sweat urea. Indirect calorimetry (protein corrected) and 13(C/12)C enrichment in expired CO(2)and blood glucose allowed exogenous (Gexo), endogenous (Gendo), muscle (Gmuscle), and liver glucose oxidation calculations. During exercise (75 min) in CHO versus C (respectively): protein oxidation was lower (6.8 +/- 2.7, 18.8 +/- 5.9 g; P = 0.01); Gendo was reduced (71.2 +/- 3.8, 80.7 +/- 5.7% P = 0.01); Gmuscle was reduced (55.3 +/- 6.1, 65.9 +/- 6.0%; P = 0.01) compensated by increased Gexo(58.3 +/- 2.1, 3.87 +/- 0.85 g; P = 0.000002). Glucose ingestion during exercise can spare endogenous protein and carbohydrate, in fed cyclists, without glycogen depletion.