## Τετάρτη, 5 Ιουνίου 2019

### Oncology

Oncologic and reproductive outcomes of cystectomy as a fertility-sparing treatment for early-stage epithelial ovarian cancer

### Background

Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking.

### Methods

After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed.

### Results

The median age was 29 years (range 26–38 years). The median follow-up time was 103.6 months (range 42.2–218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients.

### Conclusions

Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

Biweekly S-1 plus oxaliplatin (SOX) reintroduction in previously treated metastatic colorectal cancer patients (ORION 2 study): a phase II study to evaluate the efficacy and safety

### Background

The reintroduction of oxaliplatin as a third-or-later-line regimen has been a promising option for patients with metastatic colorectal cancer (mCRC) who previously received chemotherapy including oxaliplatin. In this single-arm phase II study, we evaluated the efficacy of biweekly SOX, which is the combination of oxaliplatin reintroduction and S-1, as a third-or-later-line treatment.

### Methods

Patients with mCRC who had previously received prior chemotherapy including oxaliplatin and irinotecan and were planned to receive the reintroduction of oxaliplatin were enrolled. Oxaliplatin (85 mg/m2) with/without bevacizumab (5 mg/kg) was given intravenously on day 1. Oral S-1 was administered on day 2–8 at a dose of 40–60 mg (calculated according to the body surface area) twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the progression-free survival (PFS); our hypothesis was that the median PFS would be 3.5 months with a minimum threshold above 2.0 months. The secondary endpoints included the adverse events (AEs), response rate and overall survival (OS).

### Results

A total of 41 patients from 12 institutes were enrolled. The median PFS and OS survival were 3.3 months (95% confidence interval [CI] 2.7–4.2) and 10.1 months (8.3–14.6), and response rate and disease control rate were 10.0% and 65.0%, respectively. Grade 3 AEs included thrombocytopenia (5.0%), anorexia (5.0%), pneumonia (5.0%) and fatigue (5.0%). There were no cases of grade 4 AEs or treatment-related death.

### Conclusion

Biweekly SOX regimen with reintroduction of oxaliplatin could be exploitable as the third- and/or later-line treatments for patients with mCRC.

Inflammation–nutrition score predicts prognosis of patients with resectable hepatocellular carcinoma

### Background

Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC).

### Methods

Data were collected retrospectively from 674 HCC patients who underwent curative resection. The correlation between INS (inflammation–nutrition score), BCLC (Barcelona Clinic Liver Cancer) stage and inflammatory indices and overall survival (OS) and disease free survival (DFS) was examined.

### Results

An elevated INS was associated with both tumor and host clinical characteristics. The combination of INS and BCLC stage stratifies OS and DFS from 80% and 65% (INS = 0, stage A) to 0% (INS = 2, stage C). Univariate and multivariate analyses revealed that the INS was an independent predictor for OS and DFS, and was superior to inflammation-based scores. In addition, INS was demonstrated to be a prognostic factor for patients with early stage and had a higher AUC value in comparison with inflammation scores.

### Conclusion

This study demonstrates that the INS is an independent marker of poor prognosis in patients with resectable HCC, especially for those with early stage, and it provides complimentary prognostic information to BCLC stage, and may aid in treatment strategy.

Discrimination between breast invasive ductal carcinomas and benign lesions by optimizing quantitative parameters derived from dynamic contrast-enhanced MRI using a semi-automatic method

### Background

To propose a semi-automatic method for distinguishing invasive ductal carcinomas from benign lesions on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

### Methods

142 cases were included. In the conventional method, the region of interest for a breast lesion was drawn manually and the corresponding mean time–signal intensity curve (TIC) was qualitatively categorized. Only one quantitative parameter was obtained: the maximum slope of increase (MSI). By contrast, the proposed method extracted the suspicious breast lesion semi-automatically. Besides MSI, more quantitative parameters reflecting perfusion information were derived from the mean TIC and lesion region, including the signal intensity slope (SIslope), initial percentage of enhancement, percentage of peak enhancement, early signal enhancement ratio, and second enhancement percentage. The mean TIC was categorized quantitatively according to the value of SIslope. Regression models were established. The diagnostic performance differed between the new and conventional methods according to the Wilcoxon rank-sum test and receiver operating characteristic analysis.

### Results

According to the TIC categorization results, the accuracies of the traditional and the new method were 59.16% and 76.05%, respectively (P < 0.05). The accuracy was 63.35% for MSI, which was derived from the manual method. For the semi-automatic method, the accuracies were 81.0% and 78.9% for the lesion region and the corresponding mean TIC regression models, respectively.

### Conclusions

The results demonstrate that our proposed semi-automatic method is beneficial for discriminating breast IDCs and benign lesions based on DCE-MRI, and this method should be considered as a supplementary tool for subjective diagnosis by clinical radiologists.

Analysis of major BCR-ABL1 mRNA by digital polymerase chain reaction is useful for prediction of international scale

### Background

Major BCR-ABL1 mRNA in patients with chronic myeloid leukemia (CML) has generally been analysed by real-time polymerase chain reaction (PCR). Application of the international scale (IS) for the quantification of major BCR-ABL1 mRNA has been recommended in several sets of guidelines, including those of the European LeukemiaNet. The aim of this study was to clarify the efficacy of digital PCR technology for the IS of BCR-ABL1 mRNA in the patients with CML by comparing with real-time PCR.

### Methods

The analysis of BCR-ABL1 mRNA was carried out by the Ipsogen® BCR-ABL1 Mbcr IS-MMR DX Kit (Qiagen), and the QuantStudio 3D Digital PCR System (Thermo Fisher Scientific‎) using 20 peripheral blood samples obtained from the 9 patients with CML at Sapporo Medical University Hospital.

### Results

The correlation between the data obtained by digital PCR and by real-time PCR was really high at R = 0.96. The detection limit of digital PCR was up to 0.003% and was equal to IS with 0.01% or less in comparison with real-time PCR.

### Conclusions

Digital PCR technology is promising for predicting the IS value with similar efficacy to real-time PCR and should be useful for simple monitoring of the effects of tyrosine kinase inhibitor (TKI) treatments.

Comparative assessment of prognostic outcomes between first-generation antiandrogens and novel androgen-receptor-axis-targeted agents in patients with non-metastatic castration-resistant prostate cancer

### Background

To compare the prognostic outcomes between first-generation antiandrogen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA) as first-line therapy in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

### Methods

This study retrospectively included a total of 103 consecutive nmCRPC patients consisting of 47 (45.6%) and 56 (54.4%) who received FGA (bicalutamide or flutamide) and ARATA (abiraterone acetate or enzalutamide), respectively, as the first-line agent after the failure of primary androgen deprivation therapy (ADT).

### Results

There were no significant differences in the major clinicopathological parameters and previous therapeutic histories between the FGA and ARATA groups. During the observation period, 31 (66.0%) and 29 (51.8%) discontinued first-line therapy in the FGA and ARATA groups, respectively, and of these, 27 (87.1%) and 23 (79.3%) in the FGA and ARATA groups, respectively, were subsequently treated with approved agents as second-line therapy. The prostate-specific antigen (PSA) response rate in the FGA group was significantly lower than that in the ARATA group. Although no significant difference in overall survival was noted between the FGA and ARATA groups, there were significant differences in the PSA progression-free survival on first-line therapy and metastasis-free survival between the two groups, favoring the ARATA group compared with FGA group.

### Conclusions

Collectively, these findings suggest that among nmCRPC patients who progressed following treatment with the primary ADT, the introduction of ARATA may result in the delay of disease progression compared with FGA.

A prognostic parameter in advanced non-small cell lung cancer: the ratio of hemoglobin-to-red cell distribution width

### Background

This study aims to investigate the prognostic value of the ratio of hemoglobin–RDW (HRR) at diagnosis, in terms of overall survival (OS) and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC).

### Methods

Patients with metastatic NCCLC who attended two separate medical oncology clinics between April 2013 and December 2017 were retrospectively screened. HRR was calculated as Hgb (g/dL) divided by the RDW (%). Patients were assigned to either the low HRR group or high HRR group.

### Results

A total of 153 patients were included in the study. The cuff-value for HRR was taken as 0.88. Among the low and high HRR groups, Glasgow prognostic scores (GPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and weight loss were statistically significantly different (p < 0.05). OS was found to be 5.6 months in the low HRR group and 13.9 months in the high HRR group (p < 0.001) while PFS was 5.1 months and 8.6 months in these two groups, respectively (p < 0.001). Univariate and multivariate analyses revealed that low HRR was an independent factor, predictive of both OS (p = 0.03, Hazard Ratio (HR) = 1.607, 95% CI = 1.041–2.480) and PFS (p < 0.001, HR = 2.635, 95% CI = 1.667–4.166) in advanced NSCLC.

### Conclusion

This is the first study to show that low HRR is associated with poor OS and PFS in patients with advanced NSCLC. Thus, hemoglobin and RDW which can be easily measured in routine practice may be used as a prognostic tool in these patients.

The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV

### Abstract

According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma

### Background

The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution.

### Methods

We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan–Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses.

### Results

There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively.

### Conclusion

The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Molecular carcinogenesis of gastric cancer: Lauren classification, mucin phenotype expression, and cancer stem cells

### Abstract

Gastric cancer (GC), one of the most common human cancers, is a heterogeneous disease with different phenotypes, prognoses, and responses to treatment. Understanding the pathogenesis of GC at the molecular level is important for prognosis prediction and determining treatments. Microsatellite instability (MSI), silencing of MLH1MGMT, and CDKN2A genes by DNA hypermethylation, KRAS mutation, APC mutation, and ERBB2amplification are frequently found in intestinal type GC. Inactivation of CDH1 and RARB by DNA hypermethylation, and amplification of FGFR and MET, are frequently detected in diffuse type GC. In addition, BST2 and PCDHB9 genes are overexpressed in intestinal type GC. Both genes are associated with GC progression. GC can be divided into gastric/intestinal mucin phenotypes according to mucin expression. MSI, alterations of TP73CDH1 mutation, and DNA methylation of MLH are detected frequently in the gastric mucin phenotype. TP53 mutation, deletion of APC, and DNA methylation of MGMT are detected frequently in the intestinal mucin phenotype. FKTN is overexpressed in the intestinal mucin phenotype, and IQGAP3 is overexpressed in the gastric mucin phenotype. These genes are involved in GC progression. To characterize cancer stem cells, a useful method is spheroid colony formation. KIFC1 and KIF11 genes show more than twofold higher expression in spheroid-forming cells than that in parental cells. Both KIF genes are overexpressed in GC, and knockdown of these genes inhibits spheroid formation. Alterations of these molecules may be useful to understand gastric carcinogenesis. Specific inhibitors of these molecules may also be promising anticancer drugs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

### Cancer

Hematogenous intestinal metastases from sigmoid colon cancer presenting as iliopsoas abscess and bowel obstruction

### Abstract

Intestinal metastases from colorectal cancer typically occur by intraperitoneal spread, whereas those occurring via hematogenous route are exceedingly rare. We report a case of intestinal metastases from sigmoid colon cancer that presented as iliopsoas abscess and ileus. A 78-year-old man who had undergone sigmoidectomy for sigmoid colon cancer 5 years ago was referred to our hospital with recurrent ileus and fever. Abdominal computed tomography showed a left iliopsoas abscess and a mass near the abscess that had ostensibly caused ileus. The patient underwent segmental resection of the jejunum including the mass. Histopathological examination of the resected specimen revealed moderately differentiated adenocarcinoma proliferating mainly in the submucosal and muscular layers, which was pathologically identical to the colon cancer resected 5 years ago. He died 18 months after the surgery because of liver metastases. This case report highlights the delayed occurrence of colorectal metastases at unusual sites, such as the small bowel, more than 5 years after the resection of the primary cancer. Intestinal metastases should be considered in patients with a history of colon cancer, particularly in those with recurrent ileus or abdominal abscess with no obvious cause.

The rapid improvement in visual field defect observed with weekly perimetry during intensity-modulated radiotherapy for optic nerve sheath meningioma

### Abstract

During precision radiotherapy to treat optic nerve sheath meningioma, early improvement in visual function has been seen. This has been difficult to explain biologically. In the present study, we aimed to investigate this rapid improvement in visual function. To this end, we prospectively tested a single patient's visual field (VF) using Humphrey automated perimetry at weekly intervals. The patient exhibited significant stepwise improvement in VF during an intensity-modulated radiotherapy course.

Pazopanib maintenance therapy after tandem high-dose chemotherapy for disseminated Ewing sarcoma

### Abstract

The dismal prognosis of patients with disseminated Ewing sarcoma necessitates the development of novel treatment strategies. Pazopanib is an oral multi-targeted tyrosine kinase inhibitor that is active against advanced soft tissue sarcoma. However, the clinical activity and feasibility of pazopanib for treating Ewing sarcoma remain poorly understood. Moreover, clinical information on the use of tandem high-dose chemotherapy for Ewing sarcoma is limited. A 14-year-old boy with Ewing sarcoma was transferred to our hospital for treatment. Magnetic resonance imaging, computed tomography scans, and bone scintigraphy revealed multiple lesions in the pubis, ilium, ischium, femur, rib, cranial bone, thoracic vertebrae, sacrum, obturator muscle, adductor magnus muscle, testicular cord, and lungs. Bone scintigraphy after intensive chemotherapies confirmed that multiple abnormal accumulations were still present in the cranial bone and pubis. Subsequently, the patient received tandem high-dose chemotherapy including topotecan, and radiotherapy. Abnormal accumulations have disappeared in bone scintigraphy. Subsequently, pazopanib maintenance therapy was initiated. Despite the presence of innumerable lesions at diagnosis, the patient has been in near-complete remission for the past 1 year with pazopanib administration. This confirms that adding pazopanib maintenance therapy after tandem high-dose chemotherapy is a therapeutic option for cases with disseminated Ewing sarcoma.

Radiation myelitis after durvalumab administration following chemoradiotherapy for locally advanced non-small cell lung cancer: an illustrative case report and review of the literature

### Abstract

A 69-year-old man with stage IIIB lung adenocarcinoma received durvalumab following chemoradiotherapy. The prescribed dose was 50 Gy in 2 Gy fractions, and the maximum spinal cord dose was 40 Gy. After three cycles of durvalumab, he experienced bladder and rectal disturbance, muscle weakness in the lower limbs, and sensory loss in the lower body. Magnetic resonance imaging revealed T2 signal hyperintensity involving the thoracic spinal cord. As the thoracic spinal cord with T2 signal hyperintensity matched with the irradiated site, the patient was diagnosed with radiation myelitis. This case report shows the clinical and radiographic features of a case of locally advanced non-small cell lung cancer that demonstrated radiation myelitis following durvalumab administration. The time of onset was very early and the influence of durvalumab was suspected as the cause of myelitis.

Small-cell lung carcinoma with ovarian metastasis 4 years after the first-line treatment

### Abstract

Small-cell lung carcinoma rarely metastasizes to the ovary. Only few cases of this condition have been reported to date. A 42-year-old female nonsmoker was an outpatient after receiving treatment for small-cell lung carcinoma. Approximately 45 months after the first-line treatment, the pro-gastrin-releasing peptide level exhibited a gradual increase. Positron emission tomography-computed tomography revealed abnormal accumulation in the left ovary. Accordingly, we performed laparoscopic salpingo-oophorectomy. Both pathological and immunohistochemical examinations (thyroid transcription factor-1, synaptophysin, and chromogranin A staining) led to the diagnosis of ovarian metastasis of small-cell lung carcinoma. The pro-gastrin-releasing peptide level declined postoperatively, and no recurrence has been reported thus far. Here we reported an extremely rare case of small-cell lung carcinoma metastatic to the ovary after several years of receiving the initial treatment for small-cell lung carcinoma, which, however, exhibited an excellent course postoperatively.

Primary small cell neuroendocrine carcinoma of adrenal gland

### Abstract

Neuroendocrine tumors are an extremely rare form of retroperitoneum tumor. A 79-year-old man presented with abdominal pain. Computed tomography and magnetic resonance imaging revealed a 51 × 36 mm mass in the left adrenal gland. Gastrofiberscopy, colonfiberscopy and positron emission tomography were performed and showed no lesions or other malignancies. Endocrine tests were normal. Two months later, the mass had grown to 68 × 52 mm. Suspecting a malignant tumor, we performed laparoscopic adrenalectomy. Histopathological diagnosis revealed the tumor was small cell neuroendocrine carcinoma. No other malignancies were revealed, so we diagnosed primary small cell neuroendocrine carcinoma of adrenal gland. To our knowledge, this is only the third report in English of primary small cell neuroendocrine carcinoma of the adrenal gland and the first report that is confined to the adrenal gland. Adrenal masses are often misdiagnosed as adenoma; however, we need to raise awareness of the potential for malignant adrenal tumors such as the rarer small cell neuroendocrine carcinoma.

Successful treatment of advanced gastric cancer with liver metastasis by S-1 + CDDP and S-1 therapy without surgery

### Abstract

It is generally reported that prognosis of patients who have unresectable gastric cancer is from 3 to 5 months with best supportive care. Despite the improvement of survival after the appearance of S-1, the outcome of treatment for advanced gastric cancer is still unfavorable. Here we present a valuable case of advanced gastric cancer with synchronous liver metastasis, which was treated by S-1 + CDDP and S-1 therapy without surgery. A 58-year-old man was referred to our hospital with a diagnosis of advanced gastric cancer with liver metastasis at stage of cT3N0M1. He underwent first-line chemotherapy consisting of S-1 plus cispatin. 3 months later, a follow-up endoscopy revealed complete response (CR) of the gastric lesion. 3 months later, computed tomography (CT) also demonstrated disappearance of liver metastasis. Then he underwent maintenance chemotherapy with S-1 alone for 8 months. To date, there has been no recurrence for 6 years and 6 months since the acquisition of CR.

Simultaneous chylous ascites and chylothorax during ramucirumab plus docetaxel chemotherapy in a patient with non-small lung cell cancer

### Abstract

A 69-year-old woman was diagnosed as having non-small cell lung cancer (adenocarcinoma, T1aN3M1b). She had no history of surgery or abdominal trauma. She was treated with ramucirumab (10 mg/kg) plus docetaxel (60 mg/m2) intravenously (RAM + DTX) every 3 weeks. Although an enhanced CT examination showed a partial tumor response after eight courses of RAM + DTX, she gradually began to experience abdominal fullness with severe peripheral pitching edema. Her body weight increased by 18 kg in 2 months and RAM + DTX chemotherapy was discontinued. An enhanced CT examination showed a large amount of ascites and pleural effusion, with no obstructions of the central vein or lymphatic ducts. The ascites were white and milky in appearance and contained 527 mg/dL of triglyceride. In addition, her pleural effusion was also white and milky in appearance. No further increases in ascites and pleural effusion were observed thereafter. Four months after her last RAM + DTX chemotherapy, she continued to exhibit a partial response and no increases in ascites or pleural effusion were present. The chylous effusion might have been caused by the RAM + DTX chemotherapy.

Primary tumor of the ureteral stump after a radical nephrectomy for renal cell carcinoma: case report and literature review

### Abstract

We report a case of ureteral stump carcinoma following a radical nephrectomy for renal cell carcinoma. A 76-year-old man was diagnosed as having ascending colon cancer and a right renal carcinoma. He was treated with partial colon resection and radical nephrectomy without lymphadenectomy. The histology was renal cell carcinoma. Three years after that surgery, he complained of intermittent macrohematuria. Abdominal computed tomography (CT) suggested a solid mass in the pelvis. We then performed a biopsy with CT guidance. An epithelial tumor was suspected by immunohistochemistry. A total excision of ureter was then performed. The histology showed the features of urothelial carcinoma, G3, v(+), pT3. He received adjuvant chemotherapy with gemcitabine and cisplatin. He was free of disease for the following 11 months.

Cancer-associated cerebral infarction during direct oral anticoagulant treatment in cancer patients: a case series

### Abstract

The effect of direct oral anticoagulants (DOACs) on cancer-associated cerebral infarction (CI) is unclear. We present the clinical course of 20 consecutive patients with cancer-associated CI that developed during treatment with DOACs. The incidence rate of cancer-associated CI during the treatment with DOACs was 3.4%. The median modified Rankin scale (mRS) and Karnofsky performance status (KPS) after CI were 5 and 30, respectively. The median survival time after CI was 1 month. In the group in which the thrombus due to venous thromboembolism (VTE) was reduced before CI, the median mRS, KPS, and prognosis after CI were significantly better than in those of the group with unchanged thrombus. Cancer-associated CI also developed in patients taking DOACs and those who did not show VTE recurrence. When the VTE thrombus decreased or disappeared with DOAC treatment, the clinical course after cancer-associated CI was improved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Characterisation of computed tomography angiography findings in paediatric patients with heterotaxy

### Background

Heterotaxy refers to the abnormal arrangement of organs across the left–right axis and is typically associated with complex cardiovascular malformations.

### Objective

To characterise the range of cardiac and extracardiac CT angiography findings in children with heterotaxy using the latest nomenclature consensus and to compare the different types of isomerism.

### Materials and methods

We retrospectively analysed the data of 64 consecutive paediatric patients referred to our tertiary paediatric cardiovascular centre who underwent CT angiography for the evaluation of known or suspected heterotaxy within a 52-month period.

### Results

Right atrial isomerism was identified in 44 (69%) children, while left atrial isomerism was identified in 18 (28%) children. Atrial appendage anatomy and situs could not be determined in 2 children (3%). Associated heart defects included complete atrioventricular canal (CAVC) in 51 (80%) children, total anomalous pulmonary venous return in 43 (67%) and pulmonary atresia in 23 (36%). The bronchial branching pattern corresponded to atrial appendage morphology in all children except in the two in whom atrial appendage morphology could not be defined. In children with right atrial isomerism, the most common associated abnormalities were CAVC (n=41, 93%) and asplenia (n=34, 77%), while in those with left atrial isomerism, the most common associated abnormalities were polysplenia (n=17, 94%) and an interrupted inferior vena cava with azygos continuation (n=15, 83%).

### Conclusion

CT angiography provides useful cardiovascular and extracardiac data on heterotaxy, which frequently involves a pattern of side-related findings but has great anatomical variability.

Minimally invasive treatment of pediatric head and neck dermoids: percutaneous drainage and radiofrequency coblation

### Background

Dermoids are common benign head and neck cysts in children containing a variety of different skin elements. Current standard treatment is surgical removal that sometimes requires extensive dissection to ensure complete resection and often leaves unwanted facial scarring. A minimally invasive treatment alternative should offer a similar rate of success with a decrease in operative complexity, recovery time and postoperative scarring.

### Objective

To assess the outcomes of our minimally invasive percutaneous treatment of head and neck dermoids, we reviewed our 9-year interventional radiology (IR) department experience.

### Materials and methods

The medical records, imaging and procedural details were reviewed from a cohort of pediatric patients with dermoids treated in our IR department from January 2009 through February 2018. Patients in the study underwent ultrasound (US)-guided cyst puncture, 3% Sotradecol (sodium tetradecyl sulfate [STS]) emulsification of the thick cyst contents allowing complete drainage, and radiofrequency coblation of the cyst wall.

### Results

In this retrospective study, we report on 22 dermoids in 21 patients. The average patient age was 3 years. Twenty-one of the 22 dermoids were successfully treated for an overall success rate of 95%. Four intraosseous dermoids were successfully treated using computed tomography (CT) guidance instead of, or in addition to, US. Average follow-up time was 22 months.

### Conclusion

The combination of percutaneous cyst drainage using STS as an emulsifying agent followed by radiofrequency coblation is a safe, effective, minimally invasive treatment for pediatric patients with head and neck dermoids.

Changes in factors influencing fellowship choices among radiology residents from 2008 to 2018 and methods that may increase interest in the pediatric radiology subspecialty

### Background

Fewer residents are choosing a career in pediatric radiology, which is contributing to an ongoing shortage of pediatric radiologists.

### Objective

To identify potential causes of reduced interest in pediatric radiology as a career given a projected worsening of a nationwide shortage of pediatric radiologists.

### Materials and methods

An online questionnaire using previously published questions was approved and distributed by the Program Directors in Diagnostic Radiology to diagnostic radiology residents on behalf of the Society for Pediatric Radiology (SPR). Descriptive statistics including means with standard error and independent t-tests were used to compare mean scores between survey years.

### Results

Nearly all of the 353 respondents (90.9%) planned on pursuing a fellowship. The majority (57.7%) identified their fellowship subspecialty before the 3rd year of residency with only 5.7% selecting pediatric radiology. Overall, 18.2% of survey respondents favored academic practice compared to 40% in the pediatric radiology subgroup. Fellowship choices were most strongly based on area of strong personal interest, marketability and area of strong personal knowledge, while the pediatric radiology subgroup emphasized area of strong personal interest, increased interaction with other physicians and enjoyable residency rotations. The pediatric radiology subgroup believed their impact on patient care was more significant than other subspecialties. Pediatric radiology job opportunities were thought to be more limited, geographically confining, and to have lower salaries than other subspecialties. More flexible job opportunities and higher demand were identified as factors needing to change before a resident would consider a pediatric radiology career.

### Conclusion

The influence on fellowship selection is multifactorial. By emphasizing the favorable job market and marketability of pediatric radiology in all practice types/geographic locations, correcting perceived salary gaps and stressing the impact on patient care as early as medical school, the number of residents choosing a career in pediatric radiology may grow.

The length of the intussusception increases with distal propagation of the ileocolic intussusception

Correction to: European Society of Paediatric Radiology abdominal imaging task force: statement on imaging in very early onset inflammatory bowel disease

The above article was published online with incorrect author name. The right spelling should be Damjana Kljucevsek instead of Damjana Kjucevsek. The correct name is presented here.

The length of the intussusception increases with distal propagation of the ileocolic intussusception: reply to Karmazyn et al.

Bone age for chronological age determination — statement of the European Society of Paediatric Radiology musculoskeletal task force group

### Abstract

Radiologists are sometimes requested to determine a person's age based on skeletal radiographs. Critical reviews demonstrate that this cannot be done with sufficient accuracy with existing methods.

Lionel W. Young, MD, FACR (1932–2019)

Ultrasound guidelines for pediatric thyroid nodules: proceeding with caution

Fluoroscopic practice patterns in pediatric radiology during pregnancy

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

### Air Quality, Atmosphere ,Health

Fragranced consumer products and effects on asthmatics: an international population-based study

### Abstract

Asthma is an international concern, with risks linked to air pollutants. Fragranced consumer products, such as air fresheners and cleaning supplies, have been associated with health problems such as asthma attacks and breathing difficulties. This study investigates the health and societal effects of fragranced products on asthmatics in four countries: United States, Australia, United Kingdom, and Sweden. Nationally representative population surveys (n = 1137; 1098; 1100; 1100) found that, across the four countries, 26.0% of adults (n = 1151) are asthmatic, reporting medically diagnosed asthma (15.8%), an asthma-like condition (11.1%), or both. Among these asthmatics, 57.8% report adverse health effects, including asthma attacks (25.0%), respiratory problems (37.7%), and migraine headaches (22.6%), from exposure to fragranced products. In particular, 36.7% of asthmatics report health problems from air fresheners or deodorizers, 18.1% from the scent of laundry products coming from a dryer vent, 32.9% from being in a room cleaned with scented products, 38.7% from being near someone wearing a fragranced product, and 37.5% from other types of fragranced products. For 24.1% of asthmatics, health problems from fragranced products are potentially disabling. Further, 20.6% of asthmatics have lost workdays or lost a job, in the past year, due to fragranced product exposure in the workplace. Fragrance-free environments received widespread support. More than twice as many individuals, both asthmatics as well as non-asthmatics, would prefer that workplaces, health care facilities and professionals, airplanes, and hotels were fragrance-free rather than fragranced. This study provides evidence that asthmatics can be profoundly, adversely, and disproportionately affected by exposure to fragranced consumer products. Moreover, the study points to a relatively straightforward and cost-effective approach to reduce risks; namely, to reduce exposure to fragranced products.

Household fine particulate matter (PM 2.5 ) concentrations from cooking fuels: the case in an urban setting, Wolaita Sodo, Ethiopia

### Abstract

Household air pollution from biomass fuel is a main cause of health problem in Ethiopia, since 93% of households use solid fuel for cooking. Household air pollution studies are limited in Ethiopia. Therefore, we attempted to determine the level of household fine particulate matter concentrations from cooking fuels in Wolaita Sodo town, Ethiopia. A cross-sectional study design was used to measure particulate matter (PM2.5) in 109 kitchens in randomly selected households. The University of California Berkeley particle monitor data logger devices were used for measuring the level of PM2.5 for the duration of 24 h based on the installation protocol. Descriptive statistics were used to evaluate the variation across fuel sources. Out of 109 households, 83 (76.15%) and 26 (23.85%) used predominately biomass fuel and mixed types fuel sources for cooking respectively. The overall geometric mean of PM2.5 was 413.27 μg/m3. The magnitude of PM2.5 from biomass fuel source was a mean (SD) of 926.34 μg/m3(899.00), followed by mixed type of fuel users, 279.42 μg/m3 (216.71). The median concentration of PM2.5 in all monitored households was 412.55 μg/m3. One-way ANOVA between fuel types was found to be statistically significant resulted in different mean concentration of particulate matter for both types of fuels used in households [P < 0.001]. PM2.5 was higher than the World Health Organization air quality guideline value. Therefore, supplying improved cook stoves and clean fuel sources is decisive intervention.

Change in fine particle-related premature deaths among US population subgroups between 1980 and 2010

### Abstract

A multi-decade decline in the concentrations of fine particles (PM2.5) has benefited public health greatly by reducing the incidence of premature death and illnesses. A large body of literature has examined the change over time in this burden among the US population. However, less is known about these changes have affected subgroups most vulnerable and susceptible to poor air quality. In this study, we applied the results of an air quality prediction model that estimated changes in PM2.5 between 1980 and 2010 across all counties in the contiguous US. For the year 1980, we defined groups of vulnerable and susceptible populations according to attributes including county-level educational attainment, income, urbanicity, and all-cause death rate. Using a health impact function, we quantified PM2.5-attributable premature deaths for 1980 and 2010 among the overall US population as well as these subgroups. We then used the Atkinson index to explore the inequality in the absolute level and change in PM2.5 mortality among and between these subgroups. Between 1980 and 2010, total PM2.5 mortality risk declined for all groups. Risk inequality fell across all population groups and the risk experienced among each vulnerable and susceptible group became more equitably distributed. These results suggest that falling ambient PM2.5 concentrations over a 30-year period yield significant benefits among populations most susceptible and vulnerable to poor air quality. Furthermore, our results imply that policies including the Clean Air Act were effective at reducing health disparities.

Assessment of the tools to monitor air pollution in the Spanish ports system

### Abstract

In general, seaports are located in urban areas or in their environs, whereby their activity has a very direct effect on the population. Therefore, reducing environmental contamination and improving air quality are priority management goals for port authorities (PAs). In Spain, the state-owned seaport system consists of 28 PAs that manage 46 ports. Its regulation received a major impulse through the enactment of the Spanish Ports Law in 2010. The law establishes especially the obligation that, annually, the PA prepare a sustainability report with 111 sustainability indicators. This study is founded on a database that was created with information from the reports from 2011 to 2016. A statistical analysis studies the evolution of the implementation of 20 measures for the reduction of atmospheric contamination in Spanish ports and identify the strategic lines carried out by the PAs and the measures adopted depending on the size of the ports.

Evaluating the colonization and distribution of fungal and bacterial bio-aerosol in Rajkot, western India using multi-proxy approach

### Abstract

Bio-aerosol is an emerging pollutant of the technological age. Air pollution related episodes that are a region-specific phenomenon in our atmosphere, with bio-aerosols being the main area of the problem. The present research was focused on assessing the particulate, and culturable concentration of bacteria at five different spatially located sites in the Rajkot city and surroundings, in the western part of India. The highest (108.33 × 109 CFU m−3) and lowest (318 × 103 CFU m−3) bacterial concentrations were found in dump site and residential area, respectively. With reference to particulate concentration, higher (101.79 ± 8.09) concentrations were reported in the industrial area than other sampling locations. All sampling sites under the present study displayed greater variability of bacteria than that of particle concentration. The growth potential of various bacterial isolates from perspective bioaerosol was measured spectroscopically by measuring OD at 600 nm in rich medium. The isolate 1A displayed significantly higher growth compared to all other isolates after 24 h. Outcomes of the current work suggested that bacterial concentration was observed in the respirable fraction (< 2.5 μm) and so had the potential to penetrate the deeper part of the lungs. In addition, meteorological parameters (i.e., wind speed, temperature, and relative humidity) were measured to understand whether they had any effect on biotic matter. The temperature and relative humidity are the most important meteorological parameters responsible for the enhanced viability of bacteria. Land use and land cover feature were also studied to understand the spatial characteristics of bio-aerosol in the study area. This viewpoint summarizes available information on bio-aerosols and its impact on human health, devising strategies to understand characteristics of bio-aerosols and emphasizing the vital gaps in available knowledge such as to develop a relationship between biological agents and solid/liquid or a mixture of both to the assessment of dispersion behavior and toxicological nature during exposure.

Comparison of spatial patterns of ammonia concentration and dry deposition flux between a regional Eulerian chemistry-transport model and a local Gaussian plume model

### Abstract

Agricultural activities are the principal sources of ammonia (NH3) emitted into the atmosphere. High ammonia deposition flux may impact sensitive ecosystems. Regional models of NH3 dispersion, transport and deposition may under- or overestimate NH3 fluxes. We compared NH3 dry deposition fluxes simulated with local and regional models on different theoretical scenarios characterised by varying the values of several input factors: grid cell sizes, characteristics of the NH3 sources such as location and emission rate, characteristics such as canopy resistance (Rc) or roughness length (z0) at the NH3 sinks, and meteorological conditions such as wind speed and direction. Our results showed that, for a given grid cell size, both models provide similar predictions of average NH3 concentration and dry deposition flux over the whole simulation domain. A sensitivity analysis of NH3concentration and dry deposition flux to wind speed and to surface resistance also showed a similar behaviour between both models. However, the differences of model formalism and changes in the values of the input factors, especially grid cell size and vertical resolution, provide different spatial patterns of NH3 dry deposition flux and concentration. Our results would suggest that regional models operating with large grid cell sizes (e.g. larger than 1 km) could not predict accurately patterns of NH3 dry deposition fluxes close to the sources (e.g. a few tens or hundreds of metres) on heterogeneous landscapes in terms of NH3 fluxes.

International prevalence of fragrance sensitivity

### Abstract

Emissions and exposures from fragranced consumer products, such as air fresheners and cleaning supplies, have been associated with health problems and societal impacts. This study investigates effects of fragranced consumer products on the general population in four countries: United States, Australia, United Kingdom, and Sweden. Nationally representative population surveys (n = 1137; 1098; 1100; 1100) found that, across the four countries, 32.2% of adults (34.7%, 33.0%, 27.8%, 33.1% respectively) report fragrance sensitivity; that is, adverse health effects from fragranced consumer products. For instance, 17.4% report health problems from air fresheners or deodorizers, and 15.7% from being in a room cleaned with scented products. Commonly reported health problems include respiratory difficulties (16.7%), mucosal symptoms (13.2%), migraine headaches (12.6%), skin rashes (9.1%), and asthma attacks (7.0%). For 9.5% of the population, the severity of health effects can be considered disabling. Further, 9.0% of the population have lost workdays or lost a job, in the past year, due to illness from fragranced product exposure in the workplace. Personal estimated costs due to these lost workdays and lost jobs, across the four countries in one year, exceed \$146 billion (USD). A majority of people across the countries would prefer that workplaces, health care facilities and professionals, hotels, and airplanes were fragrance-free rather than fragranced. The study highlights a concern for public health and societal well-being, as well as an approach to reduce risks and costs: reduce exposure to fragranced products.

Highly size-resolved characterization of water-soluble inorganic ions in submicron atmospheric particles

### Abstract

Up to date, few attentions have been given to the special characterization of water-soluble inorganic ions (WSIs) in the submicron atmospheric particles. In this study, to implement a highly size-resolved characterization of WSIs in the submicron atmospheric particles, ten sets of size-segregated submicron atmospheric particles were collected in Hangzhou (China) from November to December 2015, with cut-off diameters of 0.060, 0.108, 0.170, 0.260, 0.400, 0.650, and 1.000 μm. The particulate WSIs, including Cl, NO3, SO42−, Na+, NH4+, K+, and Ca2+ were analyzed by ion chromatography, and their mode distributions and potential sources were assessed. It was found that the particulate WSIs constituted a substantial part (40.4~70.9%) in each fraction of submicron particles, of which the secondary inorganic ions (SO42−, NO3, and NH4+) were the dominant species. The sulfur oxidation rate (SOR) and nitrogen oxidation rate (NOR) were increased when the submicron particles became coarser, indicating the enhanced secondary formation processes of SO42− and NO3 in the coarser submicron particles, thus resulting in the higher fractional contribution of secondary inorganic aerosols in the coarser submicron atmospheric particles. The correlation coefficients between K+ and Cl, NO3, and SO42− were 0.9293 (P = 0.002), 0.9702 (P < 0.001), and 0.9723 (P < 0.001), suggesting their dominant contribution from the biomass burning. Furthermore, it was found that PM0.4–1 (aerodynamic diameter of 0.400–1.000 μm) was a substantial part (66.6%) of submicron atmospheric particles. Compared to PM0.4 (aerodynamic diameter ≤ 0.400 μm), the concentration of WSIs in PM0.4–1 was prominently higher, and the secondary formation processes of SO42− and NO3 in PM0.4–1 were significantly enhanced.

Spatial patterns of conditions leading to peak O 3 concentrations revealed by clustering analysis of modeled data

### Abstract

Air quality models are currently the best available tool to estimate ozone (O3) concentrations in the Metropolitan Area of Buenos Aires (MABA). While the DAUMOD-GRS has been satisfactorily evaluated against observations in the urban area, a Monte Carlo (MC) analysis showed that it is the region around the MABA, where the lack of observations impedes model testing, that concentrates not only the greatest estimated O3 peak levels but also the largest model uncertainty. In this work, we apply clustering analysis to these MC outcomes in order to study the spatial patterns of conditions leading to peak ozone hourly concentrations. Results show that families of conditions distribute, as emissions, radially around the city. A cluster exhibiting an O3 morning peak dominates in low-emission areas, a behavior that can be explained both from theory and from the few monitoring campaigns carried out in the city. Its distinct dynamics compared with the typical O3 diurnal profile occurring in the urban area suggests the need of new ozone measurements in the surroundings of the MABA which could contribute to improve our understanding of O3 formation drivers in this region. The results illustrate the potential of applying clustering analysis on large ensembles of modeled data to better understand the variability in model solutions.

Ozone pollution and asthma emergency department visits in Fresno, CA, USA, during the warm season (June–September) of the years 2005 to 2015: a time-stratified case-crossover analysis

### Abstract

Fresno, located at the central part of the San Joaquin Valley (SJV), CA, USA, is one of the most air-polluted cities in North America. The present time-stratified case-crossover study investigates whether short-term exposure to ozone (O3) is associated with asthma emergency departments (ED) visits during the high O3 warm seasons (June–September) of 2005 to 2015 in Fresno, CA, USA. A total of 4463 ED visits from 2005 to 2015 in Fresno were identified. The potential effect modification by land use (commercial and residential), sex, race (White, Black, and Hispanic), and age (2–5, 6–18, 19–40, 41–64, and > = 65) was investigated. A 5 ppb increase in the concentration of O3 at the lag 0–14 was associated with 33.6% increase in the odds of having an asthma ED visit [OR 1.336 (95% confidence intervals 1.262, 1.414)]. People living in commercial areas (OR 1.470 (95% confidence intervals 1.353, 1.597) at lag 0–14) experienced higher odds of visiting the ED due to asthma when compared to those living in residential areas (OR 1.193 (95% confidence intervals 1.084, 1.313) at lag 0–14). Sex was not a modifier in this study. Blacks and Hispanics showed faster response to O3 exposure. The association between O3 exposure and asthma ED visits was positive among all age groups, but greater among 6 to 18 years. Ozone exposure is associated with asthma ED visits in Fresno during the warm seasons (June–September) of 2005 to 2015.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

### Surgical Oncology

ASO Author Reflections: An Optimal Biological Model for Successful Drug Discovery

ASO Author Reflections: Surgical Treatment for Male Breast Cancer in the Modern Era

Laparoscopic Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (L-CRS/HIPEC) for Perforated Low-Grade Appendiceal Mucinous Neoplasm (LAMN II)

### Introduction

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei resulting from a perforated low-grade appendiceal mucinous neoplasm (LAMN II). In patients with localized disease, a laparoscopic procedure (L-CRS/HIPEC) can be undertaken.

### Methods

This video demonstrates L-CRS/HIPEC in a 66-year-old male who had previously undergone an appendicectomy for an LAMN II lesion. The preoperative computed tomography (CT) scan suggested disease localized to the right iliac fossa. However, laparoscopic assessment unexpectedly revealed disease in the pelvis and on the right hemidiaphragm and liver surface.

### Results

A technique for treating the thin film of mucin in the pelvis and on the right hemidiaphragm is demonstrated. The liver is mobilized to facilitate ablation of mucin on the serosal surface of the right lobe. Tips and tricks for starting the omentectomy, dealing with the vascular pedicle, and completing the dissection in the left upper quadrant are shown. The Peritoneal Cancer Index (PCI) score was 5 (3 for the right upper quadrant, 1 for the pelvis, 1 for the small bowel), and the cytoreduction score was CC-1. The operative duration was 8.5 h, and length of hospital stay was 5 days. The patient returned to work after 6 weeks.

### Discussion

L-CRS/HIPEC can be performed when patients are unexpectedly found to have disease, provided the appendiceal pathology is low grade and the PCI score is low. There are potential benefits to this approach, with a shorter length of hospital stay and faster functional recovery when compared with traditional open surgery.

The Best Approach to Esophagectomy: Do We Know Yet?

Intrahepatic Cholangiocarcinoma: Rising Burden and Glaring Disparities

Pure Laparoscopic Anatomical Segment V Resection Using the Extrafascial and Transfissural Glissonean Approach

### Background

The Glissonean approach is a widely used, effective technique for anatomical segmentectomy using an open or laparoscopic approach.14 In the extrafascial Glissonean approach, the deep tertiary branches of the right anterior portal pedicle may be difficult to dissect from the liver hilum.5,6 We present a pure laparoscopic anatomical segment V resection using the extrafascial and transfissural Glissonean approach.

### Methods

A 49-year-old man presented with a single mass in segment 5 of the liver. (1) Dissection of the right anterior portal pedicle: the right anterior portal pedicle was dissected meticulously. After temporary clamping of the pedicle, the main and right portal fissure were delineated. (2) Opening of the main and right portal fissure: the main and right portal fissure were opened for approaching the deep tertiary segment V portal pedicle.7,8 (3) Dissection of the segment V portal pedicle: the segment V portal pedicle was dissected and the segment V territory was confirmed. After dissection of the segment V hepatic vein, the remnant liver parenchyma was transected.

### Results

The operation time was 280 min, the estimated blood loss was 80 mL, and the total Pringle maneuver time was 45 min. Final histopathological diagnosis showed a 2.8 cm-sized hepatocellular carcinoma with negative resection margin. The patient was discharged on postoperative day 6 without any complications.

### Conclusion

The extrafascial and transfissural approach in laparoscopic anatomical segment V resection is feasible and effective, and allows easy and direct access to the segment V portal pedicle.

Longer Intervals from Neoadjuvant Therapy to Rectal Cancer Surgery: The Clock is Ticking…

ASO Author Reflections: Routine Lymphadenectomy Should be Recommended Regardless of Morphologic Subtype of Intrahepatic Cholangiocarcinoma

Salvage Surgery for Jejunal Necrosis After a Free Jejunal Transfer

It Is Time

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

### Removal of rIVCFs before discharge once patients are appropriately anticoagulated is a safe strategy to improve retrieval rates.Severely injured trauma patients are at high risk of developing deep venous thombosis (DVT) and pulmonary emboli (PE), and may have contraindications to prophylactic or therapeutic anticoagulation. Retrievable inferior vena cava filters (rIVCFs) are used to act as a mechanical obstruction to prevent PE in high risk populations and those with DVT who cannot be anticoagulated.

Removal of Retrievable Inferior Vena Cava Filters before discharge
Is it associated with increased incidence of pulmonary embolism?
Robbins, Justin M., BS1; Garwe, Tabitha, PhD, MPH2,3; McCarthy, Cullen K., MD2; Sarwar, Zoona, MS2; Gonzalez, Robert A., BS1; Zander, Tyler, BS1; Jalla, Aditi N., MD2; Conner, Keri S., DO4; Stewart, Kenneth, PhD, MPH2; Albrecht, Roxie M., MD2

Journal of Trauma and Acute Care Surgery: June 3, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/TA.0000000000002395
2019 WTA Podium Paper: PDF Only
PAP
Abstract
Author Information
Article Metrics
BACKGROUND Severely injured trauma patients are at high risk of developing deep venous thombosis (DVT) and pulmonary emboli (PE), and may have contraindications to prophylactic or therapeutic anticoagulation. Retrievable inferior vena cava filters (rIVCFs) are used to act as a mechanical obstruction to prevent PE in high risk populations and those with DVT who cannot be anticoagulated.The removal rate of rIVCFs is variable in trauma centers, including our previous published rate of 50 – 89%/year. Indwelling filters carry a risk of significant morbidity and the success of retrieval decreases as the dwell time increases. We hypothesized that once patients could receive appropriate prophylactic or therapeutic anticoagulation, rIVCF could be removed before hospital discharge without impact on occurrence or recurrence of PE.

METHODS: All trauma patients with rIVCF placed and removed between 1/2006 - 8/2018 were reviewed. We collected data from record review from admission to 6 months post filter removal, including demographics, filter indication, filter type, dwell time, placement and removal complications, antithrombosis medications, location of VTE, complications, and discharge disposition. Exposure of interest was timing of filter removal: before (BEF) or after hospital discharge (AFT). The outcome of interest was whether the patient had a documented PE within 6 months of filter removal.

RESULTS: A total of 281 rIVCFs were placed, 218 were eligible for removal, 72.4% (158/218) were retrieved with 63% (100/158) removed before discharge. Mean filter duration was 26 and 103 days for the before and after group respectively. No differences (p> 0.05) were noted in the distribution of demographic and clinical factors except for filter indication (VTE indication, 95% in AFT vs 74% in BEF, p=0.0043). Post-removal PE rates were 0% BEF and 1% AFT (Fisher's Exact p=1.000).

CONCLUSIONS: Our results suggest that removal of rIVCFs before discharge once patients are appropriately anticoagulated is a safe strategy to improve retrieval rates.

Level of Evidence Level IV

© 2019 Lippincott Williams & Wilkins, Inc.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

### Genetics

Translation initiation codon (ATG) or SCoT markers-based polymorphism study within and across various Capsicum accessions: insight from their amplification, cross-transferability and genetic diversity

### Abstract

Being an economical and nutritional crop, Capsicum appeases people's peppery taste and is found to be widely distributed all over the world having vast diversity. In the present study, genetic polymorphism, cross transferability (CT) and genetic diversity were examined among the 54 different accessions of Capsicum species including 49 of Capsicum annuum, three of C. baccatum and two of Cfrutescens, using a set of 36 start codon targeted (SCoT) primers. Of the total, 35 SCoT markers showed successful amplification profile among chilli germplasms and an average primer polymorphism was reported as 81.52% which ranged from 50% (SCoT-6) to 100% (SCoT-11). A total of 365 amplicons were obtained with an average of 10.43 bands per primer and the length of the bands ranged from 150 bp to 1.2 kb. Further, polymorphic information content value of SCoT markers ranged from 0.42 (for SCoT-25) to 0.86 (SCoT-27) with an average of 0.78. The average value of CT of SCoT markers was 44.08% ranged from 14.25% to 57.26% among different chilli accessions. A dendrogram was constructed and established genetic relationship among 54 capsicum species, with the help of translation initiation codon polymorphisms or SCoT primer amplification. This study suggests the effectiveness of SCoT marker system for characterizing and assessing genetic diversity of Capsicum germplasm, which can be used for evolutionary studies and to identify agronomically important traits.

Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders

### Abstract

Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein–protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by the previous interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, $$\hbox {G}\upalpha$$ signalling and cGMP-PKG signalling pathways that are not known to be specific to SZ aetiology.

Genetic variant rs10937405 of TP63 and susceptibility to lung cancer risk in north Indian population

### Abstract

Several studies including genomewide association studies (GWASs) in diverse ethnic populations have reported a significant association of genetic variant rs10937405 of TP63 with nonsmall cell lung cancer (NSCLC). However, no data are available from any Indian population on the association of this variant with NSCLC. Using TaqMan genotyping chemistry, we conducted a case–control study involving 190 NSCLC cases and 400 ethnic, age-matched controls to explore the association of rs10937405 genetic variant with NSCLC in patients from north India. Our data support that the rs10937405 variant is also significantly associated with the NSCLC and is a risk factor in the north Indian populations to develop NSCLC. However, unlike most other studies, the wild-type allele T appears to be the risk allele, as its frequency was significantly higher in the cases than controls (0.439 in cases versus 0.383 in controls. OR = 1.95 (1.23–3.09 at 95% CI); P value (adjusted) = 0.004). Genetic association was also observed by applying different genetic models. The present study provides important information of the genetic aetiology of NSCLC and strengthens GWAS findings, highlighting the role of TP63 in lung cancer risk.

Correlation analysis of mandarin fish ( Siniperca chuatsi ) growth hormone gene polymorphisms and growth traits

### Abstract

Screening of trait-associated molecular markers can be used to enhance the efficiency of selective breeding. Previously, we produced the first high-density genetic linkage map for the mandarin fish (Siniperca chuatsi) and identified 11 quantitative-trait loci significantly associated with growth, of which one is located within the growth hormone (GH) gene. To investigate the GH gene polymorphisms and their correlation with growth, the complete sequence was cloned and 32 single-nucleotide polymorphisms (SNPs) and one simple-sequence repeat (SSR) were identified. Of which, eight SNPs (G1–G8) and the SSR (GH-AG) were selected for genotyping and correlation analysis with growth traits in a random population. The results showed that the four novel polymorphic loci (G1, G2, G3 and GH-AG) were significantly correlated with growth traits of mandarin fish ( $$P<~0.05$$ ). Of these, G1, G3 and GH-AG showed highly significant correlations with multiple growth traits ( $$P <~0.01$$ ) and the combined SNP analysis showed that G1–G3 formed four effective diplotypes (D1–D4), among which D1 was highly significantly greater than D4 ( $$P<~0.01$$ ) for some important growth traits. In conclusion, our results show that the four polymorphic loci G1–G3 and GH-AG within the mandarin fish GH gene are significantly correlated with growth traits and could be used as candidate molecular markers for selective breeding of superior varieties of mandarin fish.

'Distal 16p12.2 microdeletion' in a patient with autosomal recessive deafness-22

### Abstract

The 16p12.2 chromosome band contains three large segmental duplications: BP1, BP2 and BP3, providing a substrate for recombination and recurrent chromosomal rearrangements. The '16p12.2 microdeletion' is a recurrent deletion comprised between BP2 and BP3, associated with variable clinical findings. We identified a heterozygous 16p12.2 microdeletion spanning between BP1 and BP2 in a child evaluated for short stature and mild dyslexia. Unexpectedly, the mother carried the same deletion in the homozygous state and suffered from severe hearing loss. Detailed family history revealed consanguinity of the maternal grandparents. The 16p12.2 microdeletion is a rare condition and contains only three genes: METTL9IGSF6 and OTOA of which the OTOA is considered responsible for DFNB22 hearing loss (MIM: 607039) under its homozygous condition. A number of OTOA mutations have been described, whereas very few cases of a 16p12.2 microdeletion similar to that observed in our family have been reported. In conclusion, we describe a rare 'distal 16p12.2 microdeletion' widening the phenotypic spectrum associated with the recurrent 16p12.2 microdeletion and support the causative role of OTOA microdeletion in hearing impairment.

Development of a drought stress-resistant rice restorer line through Oryza sativa–rufipogon hybridization

### Abstract

Restorer line F6 (Oryza sativa L. ssp. indica) has been widely used in hybrid rice breeding systems in southern China. However, line F6 is susceptible to drought stress, which restricts its utilization in many areas. Dongxiang wild rice (DXWR, Oryza rufipogon Griff.) has strong drought stress resistance, but the molecular factors responsible for drought resistance in DXWR remain unknown. In this study, we used the combination of phenotypic selection and molecular marker-assisted selection (MAS) to improve the drought stress resistance of line F6 by introgression of qSDT12-2, a large effect drought stress-related quantitative trait locus identified in DXWR. Molecular MAS was carried out using linked marker RM1226, which is associated with qSDT12-2. Genomic background assessment was performed using 112 polymorphic markers. Finally, a stable drought stress-resistant backcross inbred line (BIL) was developed from a $$\hbox {BC}_{{5}} \hbox {F}_{{5}}$$ population, termed BIL627. Genetic constitution analysis revealed that the genome of BIL627 is almost identical (99.1%) to that of the restorer line F6. Further, BIL627 showed no yield penalty and no decrease in restoration ability under normal conditions. Taken together, our findings reveal the intrinsic value of using genetic resources present in wild species of Oryza to improve undesirable traits found in cultivated rice.

Genetic structure of Mediterranean fruit fly (Diptera: Tephritidae) populations from Turkey revealed by mitochondrial DNA markers

### Abstract

Ceratitis capitata is one among the most destructive and economically important agricultural pests worldwide. Despite its economic significance, the population structures of this pest have remained relatively unexplored in the eastern Mediterranean basin. Using two mitochondrial markers, the present study aimed to examining the population genetic structure and diversity of C. capitata populations in Turkey, the region that covers a large part of the eastern Mediterranean area. Our results revealed that the Turkish Mediterranean fruit fly populations are characterized by low levels of genetic diversity and limited population differentiation. For comparison purposes, we merged the sequences identified in the present study with the previously reported sequences from across the world into the data matrix. The haplotype network showed that, unlike the African samples the Mediterranean samples and samples from the new world (America, Pacific region and Australia) did not show any clear pattern of geographical structuring, which indicates that the Mediterranean basin, particularly the eastern Mediterranean region populations, may have played a more important role in the colonization of C. capitata populations to the new world. The results also revealed a close genetic relationship between the Turkish and Iranian populations, suggesting that the Iranian C. capitata populations probably originated from Turkey.

SCN2A mutation in an infant with Ohtahara syndrome and neuroimaging findings: expanding the phenotype of neuronal migration disorders

### Abstract

Neuronal migration disorders (NMDs) are a heterogeneous group of conditions caused by the abnormal migration of neuroblasts in the developing brain and nervous system, resulting in severe developmental impairment, intractable epilepsy and intellectual disability (Spalice et al. 2009). To date, many genes have been identified as the leading cause of migration defects, i.e. agyria/pachygyria, polymicrogyria, heterotopias, agenesis of the corpus callosum and agenesis of the cranial nerves (Spalice et al. 2009). Here, we present a patient with early infantile epileptic encephalopathy (Ohtahara syndrome) with seizure onset on the first day of life, severe developmental delay and an abnormal brain MRI with excessive folding of small, fused gyri and bilateral perisylvian polymicrogyria, suggestive of neuronal migration disorder. To clarify the unknown aetiology, we conducted whole-exome sequencing, which detected a de novo missense variant (c.5308A>T; p.(Met1770Leu)) in the SCN2A gene. This is a report of SCN2A gene variant identified in a patient with neuronal migration disorder which could further expand the phenotypic spectrum of these genetic disorders.

Variability of the EG95 antigen-coding gene of Echinococcus granulosus in animal and human origin: implications for vaccine development

### Abstract

In the present study, the genetic variability of the EG95 protein-coding gene in several animal and human isolates of Echinococcus granulosus was investigated. A total of 24 isolates collected from cattle, buffalo, sheep, goat, dog and man were amplified by Eg95-coding gene-specific primers. From the generated sequence information, a conceptual amino acid sequence was deduced. Phylogenetically, the Eg95 coding gene belongs to the Eg95-1/Eg95-2/Eg95-3/Eg95-4 cluster. Further confirmation on the maximum composite likelihood analysis revealed that the overall transition/transversion bias was 2.913. This finding indicated that there is bias towards transitional and transversional substitution. Using artificial neural networks, a B-cell epitope was predicted on primary sequence information. Stretches of amino acid residues varied between animal and human isolates when hydrophobicity was considered. Flexibility also varied between larval and adult stages of the organism. This observation is important to develop vaccines. However, cytotoxic T-lymphocyte epitopes on primary sequence data remained constant in all isolates. In this study, agretope identification started with hydrophobic amino acids. Amino acids with the same physico-chemical properties were present in the middle. The conformational propensity of the Eg95-coding gene of 156 amino acid residues had $$\upalpha$$ -turns and $$\upbeta$$ -turns, and $$\upalpha$$ -amphipathic regions up to 129, 138–156 and 151–155 residues, respectively. The results indicated potential T-cell antigenic sites. The overall Tajima's D value was negative (−2.404165), indicative of negative selection pressure.

Molecular characterization and expression pattern analysis of a novel stress-responsive gene ' BeSNAC1 ' in Bambusa emeiensis

### Abstract

NAC transcription factors (TFs) are master regulators of environmental stresses exerting a crucial role in plant growth and development. However, the studies on NAC TFs from Bambusa emeiensis are scarce. In this investigation, a novel gene from B. emeiensis encoding NAC protein was cloned and characterized. The gene was isolated based on the amino acid sequence data of stress-responsive SNAC1 of rice, named 'BeSNAC1 (accession no. MG763922)'. The full-length sequence of 1681 bp was found to contain an open-reading frame of 912 bp that encode a protein of 303 amino-acid residues. The multiple protein sequence alignments unveiled that BeSNAC1 contains a typical NAC domain. Additionally, the phylogenetic analysis showed that the corresponding protein belonged to the SNAC group, as it cladded with SNAC1, HvSNAC1, TaNAC2, SbSNAC1 and ZmSNAC1 proteins. Transactivation and subcellular localization assay disclosed that BeSNAC1 is a transcriptional activator localized in the cell nucleus. Moreover, the time-dependent expression pattern of BeSNAC1 was profiled under abscisic acid (ABA), polyethylene glycol 6000 (PEG-6000), NaCl, $$\hbox {H}_{2}\hbox {O}_{2}$$ and $$\hbox {Na}_{2}\hbox {SO}_{4}$$ treatments via a quantitative real-time polymerase chain reaction. The results revealed that the expression of BeSNAC1 was significantly upregulated in all treatments, a significant difference was observed under $$\hbox {H}_{2}\hbox {O}_{2}$$ , NaCl and ABA ( $$P < 0.001$$ ) and PEG and $$\hbox {Na}_{2}\hbox {SO}_{4}$$ ( $$P < 0.01$$ ) treatments, respectively. Conclusively, our findings provide evidence that 'BeSNAC1' is a nuclear protein that might act as part of the transcription regulation complex and is involved in the ABA signalling pathway and abiotic stress tolerance mechanisms in B. emeiensis.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480