BackgroundProstate cancer is morphologically and molecularly heterogeneous. Genomic heterogeneity might be mirrored by variability in DNA ploidy. Aneuploidy is a hallmark of genomic instability and associated with tumor aggressiveness. Little attention has been paid to the biological significance of the diploid tumor cell population that often coexists with aneuploid populations. Here, we investigated the role of DNA ploidy in tumor heterogeneity and clonal evolution.MethodsThree radical prostatectomy specimens with intratumoral heterogeneity based on nuclear features on H&E were selected. DNA content of each subpopulation was determined by DNA image cytometry and silver in situ hybridization (SISH). Genomic evolution was inferred from array comparative genomic hybridization (aCGH). Additionally, immunohistochemistry was used to examine the stemness‐associated marker ALDH1A1.ResultsNuclear morphology reliably predicted DNA ploidy status in all three cases. In one case, aCGH analysis revealed several shared deletions and one amplification in both the diploid and the aneuploid population, suggesting that these populations could be related. In the other two cases, a statement about relatedness was not possible. Furthermore, ALDH1A1 was expressed in 2/3 cases and exclusively observed in their diploid populations.ConclusionsIn this proof‐of‐concept study, we demonstrate the feasibility to predict the DNA ploidy status of distinct populations within one tumor by H&E morphology. Future studies are needed to further investigate the clonal relationship between the diploid and the aneuploid subpopulation and test the hypothesis that the aneuploid population is derived from the diploid one. Finally, our analyses pointed to an enrichment of the stemness‐associated marker ALDH1A1 in diploid populations, which warrants further investigation in future studies.

Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival. Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin. High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.

NUT carcinoma (NUTc) is a rare and aggressive malignant epithelial tumor characterized by rearrangement of the NUT gene on chromosome 15q14. In this article, we present the fifth case worldwide of a young woman affected by a NUTc arising from a submandibular gland, presenting as a rapidly evolving mass. She underwent a right scialoadenectomy and received the initial diagnosis of high-grade mucoepidermoid carcinoma. Due to evidence of local recurrence at magnetic resonance imaging 1 month later, a subsequent right radical neck dissection was performed. The patient then sought a second opinion at our cancer center and finally received the correct diagnosis of NUT carcinoma. Given the well-known aggressive behavior of this neoplasm, as well as clinical and radiological features, she underwent adjuvant chemo-radiation (intensity-modulated radiotherapy + concurrent chemotherapy with cisplatin). After a disease-free interval of 2.6 months, a widespread metastatic disease led to rapid deterioration of performance status and patient death in a few weeks after metastatic onset. We presented a case of NUTc arising from salivary gland aiming to improve the knowledge of this rare malignancy. First, we pointed out that in the setting of rare tumors like salivary gland cancers, the diagnosis should be obtained by expert pathologists, and patients should be referred to tertiary cancer centers for their clinical management. Second, molecular profiling may help to identify possible druggable targets that may be exploited to treat patients suffering from this aggressive malignancy. Sharing the molecular data provided in this case will be useful for further research.

Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

In patients with uterine adenosarcoma, a total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) is typically recommended as an initial treatment. There is no consensus on adjuvant therapies. We report the case of a patient with uterine adenosarcoma with postoperative residual disease. We performed four courses of adjuvant chemotherapy, including Ifosfamide, Mesna, and Adriamycin, and whole pelvic radiation with a dose of 50.4 Gy/28 Fr. A combination of chemotherapy and radiotherapy may be a promising treatment option for uterine adenosarcoma with postoperative residual disease.

BackgroundAfghanistan is in an epidemiological transition, as cancer is the second leading cause of mortality due to non‐communicable diseases. This study is the first to provide a comprehensive perspective on the overall cancer situation in Afghanistan by discussing the top five most common cancers, their incidence variations, risk factors, and preventive measures. The limited number of cancer studies conducted in Afghanistan highlights the importance of the present review.Recent FindingsThis article provides an overview of cancer burden in Afghanistan in 2020. It utilizes IARC‐generated GLOBOCAN 2020 data for one, three, and five‐year prevalence rates, the estimated number of new cancer cases, and mortality rates by age group in Afghanistan. According to GLOBOCAN, the top five common cancers in both sexes in Afghanistan were breast (n = 3173, 14.3%), stomach (n = 2913, 7.8%), lung (n = 1470, 6.6%), cervix uteri (n = 1200, 5.4%), and colorectum (n = 1084, 4.9%).ConclusionThis study provides a brief overview of the general cancer situation in Afghanistan, and a more in‐depth analysis of the five common cancers identified. Effective therapies, awareness, and prevention initiatives targeting lifestyle, immunization, early diagnosis, and environmental risk factors are essential for addressing the impact of population growth and aging on cancer incidence in Afghanistan. Further research and extensive studies are needed to better understand cancer burden in the country.

We recently reported the importance of deep learning (DL) of pelvic magnetic resonance imaging in predicting the degree of urinary incontinence (UI) following robot-assisted radical prostatectomy (RARP). However, our results were limited because the prediction accuracy was approximately 70%. To develop a more precise prediction model that can inform patients about UI recovery post-RARP surgery using a DL model based on intraoperative video images. The study cohort comprised of 101 patients with localized prostate cancer undergoing RARP. Three snapshots from intraoperative video recordings showing the pelvic cavity (prior to bladder neck incision, immediately following prostate removal, and after vesicourethral anastomosis) were evaluated, including pre- and intraoperative parameters. We evaluated the DL model plus simple or ensemble machine learning (ML), and the area under the receiver operating characteristic curve (AUC) was analyzed through sensitivity and specificity. Of 101, 64 and 37 patients demonstrated "early continence (using 0 or 1 safety pad at 3 months post-RARP)" and "late continence (others)," respectively, at 3 months postoperatively. The combination of DL and simple ML using intraoperative video snapshots with clinicopathological parameters had a notably high performance (AUC, 0.683-0.749) to predict early recovery from UI after surgery. Furthermore, combining DL with ensemble artificial neural network using intraoperative video snapshots had the highest performance (AUC, 0.882; sensitivity, 92.2%; specificity, 78.4%; overall accuracy, 85.3%) to predict early recovery from post-RARP incontinence, with similar results by internal validation. The addition of clinicopathological parameters showed no additive effects for each analysis using DL, EL and simple ML. Our findings suggest that the DL algorithm with intraoperative video imaging is a reliable method for informing patients about the severity of their recovery from UI after RARP, although it is not clear if our methods are reproducible for predicting long-term UI and pad-free continence.

The growing population of long-term childhood cancer survivors encounter a substantial burden of cardiovascular complications. The highest risk of cardiovascular complications is associated with exposure to anthracyclines and chest radiation. Longitudinal cardiovascular surveillance is recommended for childhood cancer patients; however, the optimal methods and timing are yet to be elucidated. We aimed to investigate the feasibility of different echocardiographic methods to evaluate left ventricular systolic function in retrospective datasets, including left ventricular ejection fraction (LVEF), fractional shortening (FS), global longitudinal strain (GLS) and longitudinal strain (LS) as well as the incidence and timing of subclinical left ventricular dysfunction detected by these methods. A retrospective longitudinal study was performed with re-analysis of longitudinal echocardiographic data, acquired during treatment and early follow-up, including 41 pediatric sarcoma patients, aged 2.1-17.8 years at diagnosis, treated at Astrid Lindgren Children's Hospital, Stockholm, Sweden, during the period 2010-2021. All patients had received treatment according to protocols including high cumulative doxorubicin equivalent doses (≥250 mg/m2 ). In 68% of all 366 echocardiograms, LS analysis was feasible. Impaired LS values (<17%) was demonstrated in >40%, with concomitant impairment of either LVEF or FS in 20% and combined impairment of both LVEF and FS in <10%. Importantly, there were no cases of abnormal LVEF and FS without concomitant LS impairment. Our findings demonstrate feasibility of LS in a majority of echocardiograms and a high incidence of impaired LS during anthracycline treatment for childhood sarcoma. We propose inclusion of LS in pediatric echocardiographic surveillance protocols.

ObjectivesThis study aimed to assess the superiority of 3D flexible thoracoscope against 2D thoracoscope for lymph node dissection (LND) and prognosis for prone‐position thoracoscopic esophagectomy (TE) in esophageal cancer.MethodsThree hundred and sixty‐seven esophageal cancer patients who underwent prone‐position TE with 3‐field LND between 2009 and 2018 were evaluated. 2D and 3D thoracoscope was used in 182 (2D group) and 185 cases (3D group), respectively. Short‐term surgical outcomes, numbers of retrieved mediastinal lymph node (LN), and rates of LN recurrence were compared. Risk factors for mediastinal LN recurrence and long‐time prognosis were also evaluated.ResultsNo differences in postoperative complications were observed between the groups. The numbers of retrieved mediastinal LN were significantly higher, and the rates of LN recurrence were significantly lower in the 3D group compared to 2D group. Use of 2D thoracoscope was a significant independent factor of middle mediastinal LN recurrence by multivariable analysis. Survival was compared by cox regression analysis, and the 3D group had a significantly better prognosis than the 2D group.ConclusionsProne position TE using 3D thoracoscope may improve the accuracy of mediastinal LND and prognosis without increasing postoperative complications for esophageal cancer.