[Surprising diagnosis after suspected appendicitis]. / Verrassende diagnose na verdenking appendicitis.

A 12-year-old boy presented at the emergency department because of right-sided abdominal pain. Laboratory findings and ultrasound examination were suggestive of acute appendicitis. During laparoscopy, an indurated omental mass was seen. The appendix was normal. Histopathological examination confirmed a diagnosis of omental infarction, which is rare in pediatric patients.

Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence.

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.

Unusual causes for meralgia paresthetica: systematic review of the literature and single center experience.

Meralgia paresthetica is often idiopathic, but sometimes symptoms may be caused by traumatic injury to the lateral femoral cutaneous nerve (LFCN) or compression of this nerve by a mass lesion. In this article the literature is reviewed on unusual causes for meralgia paresthetica, including different types of traumatic injury and compression of the LFCN by mass lesions. In addition, the experience from our center with the surgical treatment of unusual causes of meralgia paresthetica is presented. A PubMed search was performed on unusual causes for meralgia paresthetica. Specific attention was paid to factors that may have predisposed to LFCN injury and clues that may have pointed at a mass lesion. Moreover, our own database on all surgically treated cases of meralgia paresthetica between April 2014 and September 2022 was reviewed to identify unusual causes for meralgia paresthetica. A total of 66 articles was identified that reported results on unusual causes for meralgia paresthetica: 37 on traumatic injuries of the LFCN and 29 on compression of the LFCN by mass lesions. Most frequent cause of traumatic injury in the literature was iatrogenic, including different procedures around the anterior superior iliac spine, intra-abdominal procedures and positioning for surgery. In our own surgical database of 187 cases, there were 14 cases of traumatic LFCN injury and 4 cases in which symptoms were related to a mass lesion. It is important to consider traumatic causes or compression by a mass lesion in patients that present with meralgia paresthetica.

Undetectable anti-Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis.

OBJECTIVE: Individuals with 45,X/46,XY or 46,XY gonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti-Müllerian hormone (AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise. DESIGN, PATIENTS AND MEASUREMENTS: Individuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999-2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used. RESULTS: Thirteen males and 16 females were included, 20 with 46,XY and 9 with 45,X/46,XY DSD. Three females had dysgerminoma alongside gonadoblastoma; two gonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre-GCNIS and/or pre-gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non-(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells. CONCLUSIONS: Undetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XY or 46,XY gonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function.

Age-incidence patterns of seminoma and nonseminoma among males and females in Germany and the United States, 2008-2016.

BACKGROUND & OBJECTIVES: The comparison of the incidence of gonadal germ cell tumors among males and females can provide insights that cannot be gained by separately studying these tumors. MATERIAL AND METHODS: Incidence data on male and female gonadal germ cell tumors were drawn from the cancer registries of North Rhine-Westphalia, Germany, and the United States Surveillance, Epidemiology and End Results program, for non-Hispanic White persons only, for the years 2008-2016. We estimated age-standardized and age-, and histology-specific incidence rates. RESULTS: We included 21,840 male and 716 female gonadal germ cell tumors. Incidence rates among males were higher in Germany (95.8 per million, standard error [SE] 1.1) than in the United States (68.0, SE 0.6), while incidence rates among females were lower in Germany (1.9, SE 0.2) than in the United States (2.6, SE 0.1). The characteristic peak of infantile (age 0-4 years) germ cell tumors among males were missing among females. The age peak of ovarian germ cell tumors occurred 15-20 years earlier (Germany: 10-14 years, United States: 15-19 years) than the age peak of testicular germ cell tumors (30-34 years). The three most common testicular germ cell tumors histologies were seminoma, mixed germ cell tumors, and embryonal carcinoma Among females, the three most common ovarian germ cell tumors histologies were teratoma, yolk sac tumor, monodermal teratomas, and somatic-type tumors arising from dermoid cysts in both countries. DISCUSSION: The characteristic peak of infantile (age 0-4 years) germ cell tumors among males was missing among females. The shapes of the age-specific incidence curves are similar for males and females in Germany and the United States, though with much lower incidence rates in females, suggesting a common pathogenesis. CONCLUSION: The lower rates among females may be due to the lower number of initiated tumors in the absence of the Y-chromosome, and the earlier peak among females may be due to a younger age at puberty.

Suprainguinal Re-Resection of the Lateral Femoral Cutaneous Nerve in Persistence or Recurrence of Meralgia Paresthetica After Previous Transection: Results of a Case Series.

OBJECTIVE: Suprainguinal re-resection of the proximal nerve stump can be performed in case of persistent or recurrent symptoms of meralgia paresthetica after previous transection of the lateral femoral cutaneous nerve (LFCN). Currently, no long-term results for this procedure have been reported in the literature. METHODS: In this study, 20 consecutive patients with persistent (13 cases) or recurrent (7 cases) symptoms of meralgia paresthetica were reoperated at a mean interval of 16 months after the first transection of the LFCN. The proximal nerve stump was sent for histopathologic analysis of a potential traumatic neuroma. Outcome was assessed using a 5-point Likert scale, which was obtained at a mean interval of 3.5 years after the suprainguinal re-resection. RESULTS: The proximal stump of the LFCN was identified in 90% of the cases. Successful pain relief (Likert 1 or 2) was obtained in 65% of the patients. A neuroma was found in 11 cases (55%), mostly in recurrent cases after a pain-free interval. The indication for recurrence of symptoms more frequently resulted in successful pain relief (71%) compared with results for the indication for persistence of symptoms (62%). There was no correlation between the presence of a neuroma and the chance for pain relief. CONCLUSIONS: Suprainguinal re-resection of the LFCN can be a successful procedure, both for persistence and recurrence of symptoms of meralgia paresthetica after previous transection, with long-lasting pain relief. Several factors, however, should be considered before performing this relatively new technique in patients that are discussed in this article.

Mediastinal germ cell tumors: many questions and perhaps an answer.

Some germ cell tumors (GCTs) in men develop into hematologic malignancies; however, the clonal origins of such malignancies remain unknown. In this issue of the JCI, Taylor, Donoghue, et al. unravel the clonal relationship between primary mediastinal nonseminomas (PMNs) and hematologic somatic-type malignancies (HSTMs). Whole-exome sequencing was used to construct phylogenetic trees of the PMNs and the ensuing HSTM clones. HSTMs were derived from multiple distinct clones not detected within the PMNs. Clones from PMNs and HSTMs shared a common precursor, arguably an embryonal carcinoma cell resulting from a reprogrammed primordial germ cell from the thymus. Mutational and copy number variation analysis of a large cohort of patients with PMNs also demonstrated a high prevalence of TP53 mutations not found in testicular nonseminomas. These data likely explain why patients with PMNs are frequently resistant to platinum-based chemotherapy and provide TP53 mutations as potential targets.

[Negative pressure therapy for the treatment of severe subcutaneous emphysema]. / Negatieve-druktherapie bij ernstig subcutaan emfyseem.

BACKGROUND: Subcutaneous emphysema (SE) is the presence of air in the subcutaneous tissue. In severe cases, massive SE can lead to anxiety, pain, dyspnoea and decreased eye sight due to swelling. CASE DESCRIPTION: We describe two cases, a 75-year old male and a 66-year old male, who suffered from massive SE. When conventional therapy failed, transdermal incisions and negative pressure therapy (NPT) were applied. NPT is a commonly used method for wound care. NPT resulted in a fast relief of the SE-related symptoms in both our patients. CONCLUSION: In case of severe subcutaneous emphysema, when conventional drainage is insufficient, we recommend considering making incisions followed by the use of negative pressure therapy. This can result in a rapid drainage of the subcutaneous air, with significant relief of symptoms.

Napabucasin overcomes cisplatin resistance in ovarian germ cell tumor-derived cell line by inhibiting cancer stemness.

BACKGROUND: Cisplatin resistance of ovarian yolk sac tumors (oYST) is a clinical challenge due to dismal patient prognosis, even though the disease is extremely rare. We investigated potential association between cisplatin resistance and cancer stem cell (CSC) markers in chemoresistant oYST cells and targeting strategies to overcome resistance in oYST. METHODS: Chemoresistant cells were derived from chemosensitive human oYST cells by cultivation in cisplatin in vitro. Derivative cells were characterized by chemoresistance, functional assays, flow cytometry, gene expression and protein arrays focused on CSC markers. RNAseq, methylation and microRNA profiling were performed. Quail chorioallantoic membranes (CAM) with implanted oYST cells were used to analyze the micro-tumor extent and interconnection with the CAM. Tumorigenicity in vivo was determined on immunodeficient mouse model. Chemoresistant cells were treated by inhibitors intefering with the CSC properties to examine the chemosensitization to cisplatin. RESULTS: Long-term cisplatin exposure resulted in seven-fold higher IC50 value in resistant cells, cross-resistance to oxaliplatin and carboplatin, and increased migratory capacity, invasiveness and tumorigenicity, associated with hypomethylation of differentially methylated genes/promotors. Resistant cells exhibited increased expression of prominin-1 (CD133), ATP binding cassette subfamily G member 2 (ABCG2), aldehyde dehydrogenase 3 isoform A1 (ALDH3A1), correlating with reduced gene and promoter methylation, as well as increased expression of ALDH1A3 and higher overall ALDH enzymatic activity, rendering them cross-resistant to DEAB, disulfiram and napabucasin. Salinomycin and tunicamycin were significantly more toxic to resistant cells. Pretreatment with napabucasin resensitized the cells to cisplatin and reduced their tumorigenicity in vivo. CONCLUSIONS: The novel chemoresistant cells represent unique model of refractory oYST. CSC markers are associated with cisplatin resistance being possible targets in chemorefractory oYST.