There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.

Mucinous epithelial ovarian cancer has a poor prognosis in the advanced stages and responds poorly to conventional chemotherapy. We aim to elucidate the clinicopathological factors and incidence of HER2 expression of this cancer in a large Asian retrospective cohort from Singapore. Of a total of 133 cases, the median age at diagnosis was 48.3 years (range, 15.8–89.0 years), comparatively younger than western cohorts. Most were Chinese (71%), followed by Malays (16%), others (9.0%), and Indians (5%). 24% were noted to have a significant family history of malignancy of which breast and gastrointestinal cancers the most prominent. Majority of the patients (80%) had stage I disease at diagnosis. Information on HER2 status was available in 113 cases (85%). Of these, 31 cases (27.4%) were HER2+, higher than 18.8% reported in western population. HER2 positivity appeared to be lower among Chinese and higher among Malays patients (p = 0.052). With the current standard of care, there was no discernible impact of HER2 status on overall survival. (HR = 1.79; 95% CI, 0.66–4.85; p = 0.249). On the other hand, positive family history of cancer, presence of lymphovascular invasion, and ovarian surface involvements were significantly associated with inferior overall survival on univariate and continued to be statistically significant after adjustment for stage. While these clinical factors identify high risk patients, it is promising that the finding of a high incidence of HER2 in our Asian population may allow development of a HER2 targeted therapy to improve the management of mucinous ovarian cancers.

Polypoid endometriosis, in contrast to typical (nonpolypoid) CASE REPORTA 48-year-old nulliparous Chinese woman, who had undergone subtotal hysterectomy and left salpingooophorectomy for uterine adenomyosis and left ovarian endometriotic cyst 4 years previously, presented with heavy vaginal bleeding. Clinical examination showed an enlarged cervix. A cervical (Papanicolaou) smear was performed and was normal.Ultrasound examination showed a 4.0-cm heterogeneous cervical mass with internal vascularity and irregular polypoid extension into the left parametrium and causing left hydroureter, suspicious for cervical tumor (Figure 1a). Magnetic resonance imaging (MRI) of the pelvis revealed a 4.0 × 3.5 × 5.5-cm polypoid mass in the endocervical canal, isointense on T1-weighted imaging and heterogeneously hyperintense on T2-weighted imaging, with delayed contrast enhancement (Figure 1b). Polypoid extension into the left parametrium was noted, involving the distal left ureter and resulting in severe hydronephrosis with marked thinning of the left renal cortex. There was no invasion into the rectal lumen or urinary bladder.Examination under anesthesia showed a 3.5-cm mass in the cervical canal. Tru-cut needle biopsy of the mass showed focally ulcerated polypoid endocervical mucosa with dilated glands, granulation and thick-walled vessels but no evidence of malignancy. There was also induration of the parametria, although not involving the pelvic sidewalls. Cystoscopy and sigmoidoscopy were negative for malignancy. The patient was advised to undergo removal of the endocervical mass for symptom control.At laparotomy, an enlarged cervical stump was found with a polypoid mass in the cervical canal. There were dense fibrotic adhesions to the rectum, urinary bladder and left ureter, resulting in left hydronephrosis with pyuria. After adhesionolysis, the cervical stump was excised with the endocervical polypoid mass. Left ureterolysis and antegrade stenting were performed. The patient made an uneventful recovery and was discharged in good health.The excised cervix measured 5.0 × 3.5 × 5.5 cm and contained a 4.0 × 3.0 × 5.0-cm polypoid lesion with histological features of polypoid endometriosis. The cervical stroma was expanded by irregularly distributed islands of endometrial glands and stroma involving the entire thickness of the cervical wall, extending into the left parametrium. In some of these islands, the glands were cystically dilated and some contained intraluminal polypoid masses of endometrial tissue with features resembling endometrial polyps. The stromal component was transmural and displayed 'pseudoinfiltrative' growth but the cells showed very little mitotic activity and no features of invasion were identified. On histology, samples from around the left ureter showed dense fibrous tissue with florid endometriosis. The right ovary showed features of burnt-out endometriosis.

We report a case of neonatal intestinal volvulus around a persistent right vitelline artery, presenting as an aberrant parieto-mesenteric band on exploratory laparotomy. To our knowledge, this is the first case report in the English literature of a persistent right vitelline artery causing axial intestinal volvulus in a neonate. A review of the literature and the embryopathogenesis is discussed, as well as the importance of emergent diagnoses of such lesions.

After completing this course, the reader will be able to:1. Describe the ability of the revised 2008 FIGO staging system to determine risk strata in patients with uterine leiomyosarcoma.2. Compare concordance indices of the older and the revised FIGO staging systems.3. Identify gaps in the current FIGO staging system.