Does "One Size Fits All"? Rethinking FIGO Depth of Invasion Measurements in Vulvar Cancer.

Depth of invasion (DOI) is an important diagnostic parameter in patients with vulvar carcinoma, where a cutoff value of 1 mm largely determines the tumor stage and the need for groin surgery. DOI measurement should be reproducible and straightforward. In light of the new recommendation on how to measure DOI in the International Federation of Gynecology and Obstetrics (FIGO) staging system 2021, an exploratory study was conducted on the current practice of DOI measurement in vulvar cancer. In this study of 26 selected cases, 10 pathologists with high exposure to vulvar cancer cases in daily practice assessed both the conventional (FIGO 2009) and alternative (FIGO 2021) DOI methods for applicability and preference. In this set of cases, the DOI measurement according to FIGO 2009 was generally considered easier to apply than the measurement according to FIGO 2021, with applicability being rated as "easy to reasonable" in 76.9% versus 38.5% of cases, respectively ( P =0.005). The preferred method was FIGO 2009 or tumor thickness in 14 cases and FIGO 2021 in 6 cases. No invasion was preferred in 1 case. For the remaining 5 cases, half of the pathologists opted for the FIGO 2009 method and half for the FIGO 2021 method. Although the FIGO 2009 method proved to be more readily applicable in most of the cases studied, the method may differ for each case. There may not be a "one size fits all" solution for all cases of vulvar cancer.

Feasibility of clinical studies of chemical exchange saturation transfer magnetic resonance imaging of prostate cancer at 7 T.

Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours.

Establishment of the Dutch Nationwide, Interdisciplinary Infrastructure and Biobank for Fundamental and Translational Ovarian Cancer Research: Archipelago of Ovarian Cancer Research.

OBJECTIVES: Ovarian cancer has the worst overall survival rate of all gynecologic malignancies. For the majority of patients, the 5-year overall survival rate of less than 50% has hardly improved over the last decades. To improve the outcome of patients with all subtypes of ovarian cancer, large-scale fundamental and translational research is needed. To accommodate these types of ovarian cancer research, we have established a Dutch nationwide, interdisciplinary infrastructure and biobank: the Archipelago of Ovarian Cancer Research (AOCR). The AOCR will facilitate fundamental and translational ovarian cancer research and enhance interdisciplinary, national, and international collaboration. DESIGN: The AOCR biobank is a prospective ovarian cancer biobank in which biomaterials are collected, processed, and stored in a uniform matter for future (genetic) scientific research. All 19 Dutch hospitals in which ovarian cancer surgery is performed participate and collaborate in the AOCR biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients of 16 years and older with suspected or diagnosed ovarian, fallopian tube, or primary peritoneal cancer are recruited for participation. Patients who agree to participate give written informed consent for collection, storage, and issue of their biomaterials for future studies. After inclusion, different blood samples are taken at various predefined time points both before and during treatment. In case of a diagnostic paracentesis or biopsy, the residual biomaterials of these procedures are stored in the biobank. During surgery, primary tumor tissue and, if applicable, tissue from metastatic sites are collected and stored. From each patient, a representative histological hematoxylin and eosin stained slide is digitalized for research purposes, including reassessment by a panel of gynecologic pathologists. Clinical and pathological data are obtained on a per-study basis from Dutch registries. Research proposals for the issue of biomaterials and data are evaluated by both the Archipelago Scientific Committee and the Steering Committee. Researchers using the biomaterials from the AOCR biobank are encouraged to enrich the biobank with data and materials resulting from their analyses and experiments. LIMITATIONS: The implementation and first 4 years of collection are financed by an infrastructural grant from the Dutch Cancer Society. Therefore, the main limitation is that the costs for sustaining the biobank after the funding period will have to be covered. This coverage will come from incorporation of budget for biobanking in future grant applications and from fees from external researchers and commercial parties using the biomaterials stored in the AOCR biobank. Moreover, we will apply for grants aimed at sustaining and improving research infrastructures and biobanks. CONCLUSIONS: With the establishment of the Dutch nationwide, interdisciplinary Archipelago of Ovarian Cancer Research infrastructure and biobank, fundamental and translational research on ovarian cancer can be greatly improved. The ultimate aim of this infrastructure is that it will lead to improved diagnostics, treatment, and survival of patients with ovarian cancer.

Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer.

Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. As evidenced for HSV-1, organoid-based cervical models may serve to study sexually transmitted infections. Starting from Pap brush material, a small biobank of tumoroids derived from affected individuals was established that retained the causative human papillomavirus (HPV) genomes. One of these uniquely carried the poorly characterized HPV30 subtype, implying a potential role in carcinogenesis. The tumoroids displayed differential responses to common chemotherapeutic agents and grew as xenografts in mice. This study describes an experimental platform for cervical (cancer) research and for future personalized medicine approaches.

What are the odds? Prostate metastases to ureter and peritoneum.

In patients with prostate cancer, metastases mostly develop in bone, lung, liver, pleura and adrenal glands. Prostate carcinoma metastases to the ureter are very rare, and the peritoneum is an even rarer site of prostate metastases. We present two cases of ureteral metastases of prostate cancer, of which one patient also developed malignant ascites and peritoneal metastases. An overview of the literature on these metastatic sites is also provided. Both patients presented with hydronephrosis and a ureteral mass. Biopsies of the masses were taken, which showed the presence of prostate carcinoma metastases. The first patient was treated with chemotherapy but was diagnosed with progressive disease and died 3 years later. The second patient was diagnosed with pathology-confirmed peritoneal metastases 8 months later. He died 2 years after presentation with hydronephrosis.

Expression of nuclear FIH independently predicts overall survival of clear cell renal cell carcinoma patients.

AIM: The hypoxia inducible factor (HIF) pathway plays an important role in sporadic clear cell renal cell carcinoma (ccRCC) by stimulating processes of angiogenesis, cell proliferation, cell survival and metastases formation. Herein, we evaluate the significance of upstream proteins directly regulating the HIF pathway; the prolyl hydroxylases domain proteins (PHD)1, 2 and 3 and factor-inhibiting HIF (FIH), as prognostic markers for ccRCC. METHODS: Immunohistochemical marker expression was examined on a tissue microarray containing tumour tissue derived from 100 patients who underwent nephrectomy for ccRCC. Expression levels of HIF, FIH and PHD1, 2 and 3 were correlated with overall survival (OS) and clinicopathological prognostic factors. RESULTS: HIF-1α was positively correlated with HIF-2α (p<0.0001), PHD1 (p = 0.024), PHD2 (p<0.0001), PHD3 (p = 0.004), FIH (p<0.0001) and VHL (p = 0.031). HIF-2α levels were significantly associated with FIH (p<0.0001) and PHD2 (p = 0.0155). Mutations in the VHL gene, expression variations of HIF-1α, HIF-2α and PHD1, 2, 3 did not show a correlation to OS or clinicopathological prognostic factors. Tumour stage, grade, diameter, metastastic disease and intensity of nuclear FIH were significantly correlated to OS in univariable analysis (p = 0.023). Low nuclear FIH levels remained a strong independent prognostic factor in multivariable analysis (p = 0.009). CONCLUSION: These results show that low nuclear expression of FIH is a strong independent prognostic factor for a poor overall survival in ccRCC.

In vivo bladder cancer diagnosis by high-volume Raman spectroscopy.

We studied the feasibility of Raman spectroscopy for the diagnosis of bladder cancer in vivo. Since the invasion stage is crucial for the treatment choice, a high-volume based Raman probe was used to investigate the potential of determining the invasiveness of bladder cancer. High quality spectra were obtained from suspicious and nonsuspicious bladder locations during the procedure of transurethral resection of bladder tumors (TURBT) with collection times of 1-5 s. Multivariate analysis was used to generate the classification models. The algorithm was able to distinguish bladder cancer from normal bladder locations with a sensitivity of 85% and a specificity of 79%. The Raman spectra of bladder cancer stages showed a gradual increase in the intensity of specific amino acid peaks and, most likely, an increase in the intensity of DNA peaks.