ABSTRACT We recently performed two studies exploring the presence of Epstein–Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human colorectal cancers from the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in colorectal cancers from Syria. We reveal that 17 (~17%) of 102 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high/intermediate grade invasive carcinomas. These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they might cooperate on the initiation and/or progression of these cancers. Thus, we believe that future studies are necessary to confirm the co-presence of these oncoviruses and their cooperative role in human colorectal carcinogenesis.

Glycogen-rich clear cell carcinoma (GRCC) is a very rare form of primary breast cancer (<0.1% of all breast cancers). It is characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm (the Periodic Acid Schiff–positive, diastase-sensitive). The expression of steroid receptors (estrogen and progesterone receptors) has been variably reported (35% to 100% of the cases), whereas most studies reported low human epidermal growth factor receptor 2 positivity in GRCC. High androgen receptor positivity without androgen receptor splice variant-7 was reported in one recent study. Although sparse, the preliminary theranostic data on GRCC indicate the potential of targeted treatments in selected cases (antiandrogen, PIK3CA, and immune checkpoint inhibitors). Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy.

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcome. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2mm2, necrosis, lymphatic invasion and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlate with clinical outcome. Based on our analysis, we consider that the separation of low and intermediate grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of over grading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcome.

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.

INTRODUCTION Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome. MATERIALS AND METHODS Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. RESULTS The majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre- and post-chemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases). CONCLUSIONS Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease.

Individually, trauma and appendicitis are some of the most common conditions in clinical practice, particularly in emergency medicine. In rare cases, trauma and appendicitis may co-exist, imposing a dilemma of whether these are only coincidence or appendicitis develops because of trauma. We report here a case of acute perforated appendicitis after a blunt abdominal trauma caused by a horse hoof kick to the abdomen in a 7-year-old boy. We also discussed the potential pathophysiologic mechanisms behind and reviewed the literature on this rare condition.

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.

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.