Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

A preterm female infant with a birthweight 1770 g was born via spontaneous vaginal delivery at 34 weeks’ gestation to a 21-yearold mother who received an adequate prenatal care. Routine prenatal ultrasound at 30 weeks revealed a proximal dilatation of the gut and polyhydramnios. At delivery, initial physical exam revealed a soft ‘scaphoid’ abdomen. Apgar score was 7 and 8 at 1st and 5th minute, respectively. A nasogastric tube (NGT) was placed for gastric decompression and bilious drain was observed. Post-natal erect X-ray of the abdomen showed dilated loops in the upper abdomen with the paucity of gas in the pelvis and confirmed proximal bowel obstruction (Fig. 1). After 24 h of stabilisation and care in the neonatal intensive care unit, the patient was taken to the operating room for surgical repair of her presumed jejunal atresia. Surgical exploration revealed a markedly distended atretic jejunum with a ‘type 3B’ intestinal atresia (apple-peel jejunal atresia) and a significant loss of intestinal length. The proximal end of the jejunal atresia was located 15 cm below the ligament of Treitz. On the distal end of ileal atresia, there were two multiple ileal atresias, each 7 cm of length. Approximately, 55 cm of the small bowel distal from the ileal atresias was found to be patent (Fig. 2a). In our case, the total length of small intestine was 70 cm (15 cm distal to the ligament of Treitz and 55 cm proximal to the ileocecal valve). All atretic segments were resected. The remaining segments were preserved (without tapering proximal jejunoplasty) and connected with the end-to-end jejunoileal anastomosis using 5/0 polyglactin sutures in the single extramucosal layer employing the Cheatle technique for size mismatch (Fig. 2b). Appendectomy was also performed. Post-operatively, the patient was placed on mechanical ventilation and extubated on the 6th post-operative day (POD). Total parenteral nutrition (TPN) via a central line along with enteral nutrition via NGT were administered and lasted until the 39th POD. After 2 weeks, enteral feeding gradually improved, so the baby started receiving peroral nutrition via bottle. The patient achieved her full enteral intake on POD 38. The baby was discharged from the hospital on POD 46 with highly improved body weight – 2485 g. At the follow-up of 9 months (Fig. 3), the baby was doing well with a body weight of 7500 g.

Background: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency associated with prematurity. Timely diagnosis and adequate treatment are crucial to reduce the morbidity and mortality of the affected infants. The aim of this study was to evaluate the diagnostic yield of bowel dilatation on plane abdominal radiography (AR) in the early diagnosis and NEC severity in preterm infants. Methods: We retrospectively reviewed initial ARs of 50 preterm infants with NEC ≥ stage II admitted to the neonatal intensive care unit (NICU) in a tertiary-care hospital. The largest bowel loops diameters (AD), the latero-lateral diameters of the peduncle of the first lumbar vertebra (L1), and the distance of the upper edge of the first lumbar vertebra and the lower edge of the second one, including the disc space (L1–L2), were measured. All anteroposterior ARs were done in a supine projection on the day of onset of the initial symptoms of NEC. Results: Preterm infants with surgical NEC showed a statistically significant increase in the AD/L1 ratio (p < 0.001) and AD/L1-L2 ratio (p < 0.001) compared with preterm infants with medical NEC. We found no significant association between the site of the most distended bowel loop and the severity of NEC (p > 0.05). Conclusion: Bowel loop distension on initial AR may serve as an additional diagnostic tool in the early diagnosis and severity of stages II/III NEC. Further prospective clinical studies should validate the results from this study.

Primary Extra‐mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known.

Penile torsion is a rare congenital anomaly that is usually characterized by a counterclockwise rotation of the penile shaft or glans. Although several surgical techniques for its correction have been proposed, the consensus of choosing the most efficient technique remains controversial. Herein, we report our operational approach that successfully corrected a severe (>90 degrees) isolated penile torsion in the form of penile degloving and dorsal dartos flap rotation surgery.

Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.

Breast cancer consists of several intrinsic molecular subtypes, providing the basis for clinical treatment decisions. Lately, it is becoming increasingly recognized that factors other than the intrinsic cancer characteristics, such as immune components’ activity in the tumor microenvironment, have important effects on treatment choices and efficacy. bioSyntagma has developed a method, the Molecular Fingerprint (mPrint®), that enables multiplexed analysis of spatially defined regions in formalin-fixed, paraffin-embedded (FFPE) tumor samples allowing for analysis of the gene signatures unique to the tumor microenvironment. This method was applied to molecularly defined sets of breast cancers and used to evaluate four different tumor regions of interest (ROIs): 1) viable carcinoma proper (>90% cancer cells), 2) fibrotic tumor center (sparse cellularity), 3) interface between viable tumor and inflammatory component (tumor and inflammatory microenvironment) and 4) tissue away from the tumor (normal breast tissue). This was compared to the whole tissue scrapes from each patient block. Each ROI and tissue scrape was analyzed by high throughput qPCR for a panel of 248 genes using SmartChip technology (Takara Bio, USA). Sequential tissue slices from each patient were also analyzed using immunohistochemistry (IHC) for three targets and investigated for correlation with qPCR results for validation of the method. Overall, reasonable concordance was observed in general expression trends between selected IHC and RNA expression. qPCR data were further analyzed using hierarchical clustering analysis and showed that morphologically defined ROI’s cluster completely differently than traditional clustering of entire tissue scrapes. Notably, patient clustering based on morphological regions was independent of the intrinsic cancer subtype, as determined by molecular profiling of whole tissue scrapes, as well as independent of trends in Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). These findings suggest that current methods of patient stratification based on whole tumor molecular subtyping may be inferior to stratification based on molecular characteristics of the tumor microenvironment. Citation Format: Colleen Ziegler, Isaiah Slemons, Chris DeSilva, Barbara Witkowski, Alain Mir, Sangeetha Anandakrishnan, Andrew Farmer, Elma Contreras, David Richardson, Semir Vranic, Zoran Gatalica, Dmitry N. Derkach. Novel method for patient stratification in breast carcinoma based upon spatial analysis of tumor microenvironment [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B094. doi:10.1158/1535-7163.TARG-19-B094

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non‐canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low‐ (LGSC) and high‐grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real‐time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients’ outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations.

Predatory journals refer to journals that recruit articles through aggressive marketing and spam emails, promising a quick, but not robust, review and fast open-access (OA) publication, thus compromising scholarly publishing standards.1–5 Their key motive is a financial benefit via article processing charges (APCs) and other additional fees.1 3 4 The number of OA journals has dramatically risen over the past 15 years,6 reaching 11 376 journals, indexed in the Directory of Open Access Journals (DOAJ) in 2018 (available at https://doaj.org). This expansion was parallel to the increase in the number of predatory publishers.7 8 Predatory journals have become more prevalent than ever due to massive internet expansion and extensive spam email soliciting.2 4 9 Since 2011, when Jeffrey Beall launched his first list of potential predatory OA publishers and journals, predatory journals have come into focus.3 4 Recent studies have highlighted the significant burden of potentially predatory journals in several biomedical specialties, including neuroscience/neurology, urology, emergency medicine, physical medicine, orthopaedics, rehabilitation, as well as anaesthesiology.7 8 10–13 No study on predatory journals in pathology has been conducted so far. As previously suggested, we explored Beall’s list of predatory journals as an initial database of suspected journals related to pathology.2 8 The term predatory was only applied after assessing each journal separately. The assessment was based on the recommended …

Introduction/Background Aberrant Hedgehog (Hh) pathway signaling has been implicated in pathogenesis of several human cancers. Recent studies have indicated its active role in serous ovarian carcinomas. Smoothened protein (SMO), a transmembrane co-receptor in Hh pathway signal transduction, is inhibited in non-dividing cells, thus its disinhibition might be a trigger for uncontrolled cell proliferation and growth. Very few studies have explored the role of SMO in serous ovarian cancers. The aim of the study was to assess the expression of SMO protein and to explore the Smoothened gene promoter methylation in a cohort of serous ovarian carcinomas. Methodology SMO protein expression was immunohistochemically quantified in 40 high-grade serous carcinomas (HGSC), 12 low-grade serous carcinomas (LGSC), 20 normal ovarian and 9 normal fallopian tube samples (controls). SMO gene promoter methylation status was analyzed using methylation-specific polymerase chain reaction (MSP) in randomly selected HGSCs (n=10), LGSCs (n=10), and normal fallopian tube (n=9) samples. Kaplan-Meier survival plots were used to estimate the impact of SMO expression on patients‘ overall survival (OS). Results SMO nuclear expression was significantly higher in HGSCs and LGSCs compared with the fallopian tube samples (p=0.010 and p=0.003, respectively). LGSCs, compared with normal ovarian tissue, exhibited higher total, cytoplasmic/membrane and nuclear expression (p=0.000, p=0.001 and p=0.000, respectively). Comparing HGSCs and LGSCs, significantly higher total and cytoplasmic/membrane expression was found in HGSC (p=0.026 and p=0.030, respectively). SMO gene promoter was unmethylated in both LGSCs and HGSCs as well as in fallopian tube. In addition, the SMO protein expression had no significant impact on patients‘ OS (p=0.07). Conclusion Our data indicate the lack of SMO gene promoter methylation while a significant overexpression (particularly nuclear) of SMO protein characterized a substantial proportion of serous ovarian carcinomas. Further functional studies should elucidate the clinical relevance of these findings. Disclosure Nothing to disclose.