Late Symptoms Research Articles

Efficacy of Proton Beam Therapy for Hepatocellular Carcinoma With Portal Vein or Inferior Vena Cava Tumor Thrombosis

Vascular invasion, such as portal vein tumor thrombosis (PVTT) and inferior vena cava tumor thrombosis (IVCTT), is a common condition in advanced hepatocellular carcinoma (HCC). HCC patients with PVTT or IVCTT have an extremely poor prognosis. In order to clarify the clinical outcome of proton beam therapy (PBT) for HCC with PVTT or IVCTT, this prospective study was performed. This was a clinical study for HCC with PVTT or IVCTT using PBT based on protocols determined at Nagoya Proton Therapy Center. The primary and secondary endpoints were overall survival (OS) and complication rates, respectively. The number of patients required for this study was estimated to be 31 using the chi-square test (type 1 error=0.05, power=0.8, P0=0.3, P1=0.6). Response after PBT was evaluated using modified RECIST. OS rates were calculated using the Kaplan-Meier method and were compared using the log-rank test. Toxicities were graded according to the common terminology criteria for adverse events (v4.03). Between September 2013 and January 2017, 34 patients (27 males and 7 females) were enrolled, assuming dropout of a few patients. The median follow-up period was 8.4 months (interquartile range (IQR), 4.7-19.1). Median patient age was 68 years (IQR, 61-73). Twenty patients had Child-Pugh A liver function, 12 had Child-Pugh B, and 2 had Child-Pugh C. Etiology of HCC was hepatitis B (7), hepatitis C (18), alcoholism (5), autoimmune hepatitis (1), and nonalcoholic steatohepatitis (1). Median alpha-fetoprotein and PIVKA-II levels were 171.2 ng/mL (IQR, 28.9-5241.3) and 2620 mAU/ml (IQR, 135-12800), respectively. Median gross tumor volume was 220.0 ml (IQR, 87.6-620.6). The median biologically effective dose 10 (BED10) was 81.3 GyE (IQR, 75-96.6). Twenty-one (62%) lesions achieved a complete (15%) or partial response (47%). Stable and progressive diseases were observed in 12 (35%) and 1 (3%), respectively. Tumor thrombosis was present in the portal vein trunk (15), portal vein branch (18), or inferior vena cava (8). The 1-year OS rate was 55%. Eighteen patients in whom all tumors could be included in the irradiation field had good prognoses (P<0.05). The prognoses of 16 patients whose tumor thrombosis shrank after irradiation were good (P<0.05). One patient had grade 3 acute dermatitis. Grade 3 liver enzyme elevation was observed in 2 patients at 3 months after radiotherapy. However, no severe radiation-induced liver disease was observed. No late gastrointestinal symptoms with grade 3 or higher toxicity, such as ulceration, bleeding, perforation, and ileus were recorded. PBT for advanced HCC with PVTT or IVCTT is a safe and effective treatment without severe complications. When all the tumors can be included in the irradiation field, PBT may be effective even for large HCC.

Intrathecal Pump Refills, Pocket Fills, and Symptoms of Drug Overdose: A Prospective, Observational Study Comparing the Injected Drug Volume vs. the Drug Volume Effectively Measured Inside the Pump

One complication associated with the refill procedure of intrathecal drug delivery systems (IDDSs) include a "pocket fill," which is the inadvertent injection of the drug into the subcutaneous space surrounding the pump. The purpose of our study was to assess the mean volume discrepancy between the injected and the effective drug volume inside the IDDS reservoir after refills that did not lead to signs of overdose and to record at which volume discrepancy symptoms of overdose were noticed. After 221 refill procedures performed in 19 adult patients, drug volume inside the reservoir was assessed with a fill level sensor, and the volume discrepancy between injected and measured volume was recorded. Symptoms of overdose were monitored. For between group comparisons the Mann-Whitney U test was used, using a p-value of <0.05 to indicate statistical significance. The median volume discrepancy in the 20 mL IDDSs was 0.40 mL (IQR: 0.18-0.61; 10th p: 0.0; 90th p: 0.74) whereas in the 40 mL IDDSs the median volume discrepancy was 1.3 mL (IQR: 1.06-1.74; 10th p: 0.81; 90th p: 2.2). Symptoms of overdose were observed after 6 out of the 221 refill procedures. Volumes at which the symptoms of overdose arose were between 1.15 and 4.5 mL in 20 mL IDDSs and between 2.08 and 4.88 mL in 40 mL IDDSs. A volume discrepancy of >1 mL in 20 mL IDDSs and of >2 mL in 40 mL IDDSs after refill should be regarded as potentially consequential with regard to risk of overdose possibly caused by a pocket fill. In case of potentially consequential volume discrepancies, hospitalization and monitoring is recommended to preclude late overdose symptoms outside the hospital.

Conservative post-natal management of antenatally diagnosed congenital pulmonary airway malformations.

Management of congenital pulmonary airway malformations (CPAM) is controversial, especially for asymptomatic patients. We aim to describe the clinical manifestations and management of CPAM at a tertiary paediatric hospital using a retrospective audit. Infants with CPAM were identified on the Fetal Diagnostic Unit database from 2007 to 2014. Information on antenatal and post-natal management was collected from medical record. Thirty-five infants with antenatally diagnosed CPAM were included. Fetal CPAM volume ratio (CVR) was calculated from antenatal ultrasound measurement and used to categorise the infants into three groups of large (CVR ≥ 1.6, n = 8), medium (CVR of 0.5-1.6, n = 12) and small CPAM (CVR of ≤0.5, n = 15), respectively. Ten infants (10/35 = 29%) were symptomatic in the neonatal period. Overall, nine infants (26%) had surgical resection, among whom eight had large or medium-sized CPAM lesions as defined by the antenatal CVR. Three infants had neonatal emergency surgery and the remaining six had late elective surgery. Histology of eight cases showed CPAM, but one case showed congenital lobar emphysema. Criteria for surgery varied and included persistent symptoms after birth, complications during childhood and persistently abnormal chest X-ray. Most asymptomatic infants with CPAM were safely managed using a conservative approach, with no significant increase in late symptoms or complications. Conservative management of CPAM may be considered for infants/children who remain asymptomatic, especially those with a small lesion. For large and medium-sized CPAM, delineation using computed tomography is required, and surgery may be beneficial to prevent late symptoms and the risk of emergency surgery.

Prospective study of quality of life after lung cancer resection: using patient reported outcomes to assess the patient’s voice

Hopkins and colleagues should be commended for their effort in investigating quality of life (QOL) and postoperative pain as primary outcomes of a study comparing VATS with standard thoracotomy in cancer patients. The investigators concluded that the two approaches didn’t differentiate in terms of late QOL and pain related symptoms.

Incidence of Late Severe Urinary Symptoms after Radical IMRT for Prostate Cancer: Effect of Bladder Doses and Hypofractionation

Incidence of Late Severe Urinary Symptoms after Radical IMRT for Prostate Cancer: Effect of Bladder Doses and Hypofractionation

Diabetes-Associated Biobanking: More Topical Than Ever?

The increasing prevalence of diabetes and its accompanying long-term complications, as well as the associated economic burden, calls for a rapid clinical translation of biomedical research to better valid the physiological relevance of the findings from basic research. To meet this condition, the Collaborative Research Center (CRC) 1118 has established the first nationwide diabetes-specific Biomaterialbank (BMB) that permanently preserves solid and liquid specimen retro- and prospectively at the Institute of Pathology and Department of Endocrinology of the University Hospital Heidelberg. The main purpose of this BMB is to collect, preserve, characterize and provide human diabetic specimen to researchers investigating the role of reactive metabolites (RM) as cause of diabetic late complications. In this review we discuss the urgent need to support translational and clinical research projects by making use of diabetic solid and liquid specimen and provide an insight into the organization and general conditions of biobanking procedures which are pivotal to guaranteeing high-quality human biomaterial. In light of diabetes-tailored biobanking, we describe our newly initiated activities and introduce the diverse technology platforms that can be used for the investigation of promising molecular targets pertinent for diabetes. With this article we demonstrate that the preservation of rare specimen is also particularly relevant in the non-neoplastic field and contributes to basic investigation, promotes comprehensive scientific data and fortifies the sustainability for diabetes research. In addition, the increased understanding of how metabolic imbalance triggers diabetes onset and progression and favors diabetic late symptoms might hold some promise for future innovative diagnostic and/ or therapeutic applications, eventually adding to the improvement of patient care.

The Knowledge of South African Men Relating to Cervical Cancer and Cervical Cancer Screening.

Cervical cancer is the second most common cancer in South African women, but the most common cancer in Black women. Despite having a national cervical cancer screening programme, most women present with advanced disease. Men play a role in cervical cancer as the HPV, the major cause of cervical cancer, is sexually transmitted. The purpose of our study was to describe the knowledge men, living in Muldersdrift, had about cervical cancer, cervical cancer screening and the cervical cancer screening programme and how they preferred to be taught about these health issues. We used a survey design and convenience sampling to select 101 men older than 18years (n=101). A pretested self-developed questionnaire was used as the data collection instrument, and the data were analyzed using the SPSS version 22-computer program and quantitative content analyses. The Fischer's exact test measured associations between variables (p=0.05). The ages of the sample (n=101) ranged from 18 to 92years; most were from the Zulu cultural group, unemployed and unmarried. The majority (66.3%, n=67) had not heard of cervical cancer, the cervical cancer screening programme (60.4%, n=61) or the Pap smear (67.3%, n=68). Age and educational level did not influence having ever heard of these health issues. HPV infection was the most well-known risk factor, and the very late symptoms of cervical cancer were the least known. Most men preferred to be educated in a group, which provided a practical, feasible and cost effective way of educating men living in this community about these health issues.

P30.01: Neuroendocrine tumours of the female genital tract: a small case series

Both primary and secondary gynecological neuroendocrine tumours (NET) or carcinoid tumours are uncommon, and there is very little literature regarding their features on ultrasound (US) examination of the pelvis. The aim of this study is to describe the clinical and US features of NET of the female genital tract. Patients with a confirmed histological diagnosis of NET, who had undergone a transvaginal US in our Gynecology Assessment Clinic 2007-2016, were identified using data from histopathology laboratory and our clinical data base. King's College Hospital is a regional centre for the treatment of gastrointestinal NET. The ultrasound scans were performed by an experienced US examiner and described according to IOTA or IETA criteria as appropriate. Eight patients were identified in total. There were 4 cases of metastatic tumours in women already known to have had NET of the gastro-intestinal tract. These women had minimal or no symptoms and they were referred for surveillance CT scans. The US imaging in these tumours showed solid, irregular, hypoechoic heterogeneous tumours. The ovarian lesions were bilateral. Subjective assessment of vascularity of the tumours varied between scores of 1 to 3. One woman had a primary endometroid tumour with neuroendocrine differentiation. She presented with cerebellar metastasis and only complained of postmenopausal bleeding as a relatively late symptom. Her tumour was solid, heterogeneous, irregular and poorly vascularised on US examination. The remaining three patients had foci of NET found within dermoid cysts, none of which were suspected on preoperative US and none of whom have had recurrent disease. NET of the female genital tract tend to be multiple and solid in morphology. These tumours are much rarer than breast, stomach, lymphatic or colorectal cancers as a cause of ovarian metastases, but should be added to the list of differential diagnoses when solid tumours are found in the pelvis.

The time-sensitive challenge of diagnosing spinal epidural abscess in the emergency department.

Spinal epidural abscess (SEA) is a rare but devastating condition. Entry of infectious contents into the epidural space occurs via contiguous infected tissue, hematogenous spread, or iatrogenic inoculation. Traditionally, emergency providers are taught to assess for the "classic triad" of spinal pain, fever, and neurological deficits, but this constellation of findings is seen in only 10-15% of cases. Delays in diagnosis and treatment of this condition directly correspond to worse, and often debilitating, outcomes for these patients. This review will demonstrate the challenges of diagnosing SEA, describe key diagnostic pitfalls, and present a model and framework for its evaluation. The authors conducted a systematic review in PubMed and Google Scholar for articles describing the emergency medicine evaluation and management of spinal epidural abscess dating from 1996 to 2016. Of the initial 219 articles found, 18 articles were selected based on their relevancy to emergency medicine. Lower back pain is a common chief complaint, whereas SEA is a rare condition and may not be anticipated. The "classic triad" of SEA symptoms presents infrequently. Moreover, the early symptoms of back pain and fever are non-specific, and patients seek medical attention at varying stages of disease progression. Once the more conspicuous and wide-ranging neurological symptoms develop, they are often irreversible. In fact, final outcomes correlate with the severity and duration of symptoms before surgery. Furthermore, discovering these late neurological symptoms can be particularly difficult in bed-bound and chronically ill patients. MRI is the best diagnostic imaging tool for SEA. Early diagnosis is the major prognostic factor for favorable outcome of SEA, and yet, making this diagnosis in the emergency department (ED) has proved challenging. Shifting from a "classic triad" screening to a risk factor-based model of evaluation represents the current optimal strategy for diagnosing SEA. An algorithm incorporating the most recent data is provided.

Symptom burden as a driver of decisional regret in long‐term oropharyngeal carcinoma survivors

The purpose of this study was to characterize decisional regret and its association with symptom burden in a large cohort of oropharyngeal carcinoma (OPC) survivors. A cross-sectional survey was administered to 1729 OPC survivors. Survey items included a multisymptom inventory and a validated decisional regret inventory. Associations between regret and symptom scores were analyzed to determine and rank symptom drivers of decisional regret. Nine hundred seventy-two patients responded reporting a low level of decisional regret overall, although 15.5% communicated "moderate to strong" regret. Overall symptom score and treatment group were statistically significant predictors of decisional regret. Relative to other symptoms, difficulty swallowing and feeling sad were the strongest drivers of decisional regret. OPC survivors provide a robust description of their long-term outcomes with 15.5% expressing "moderate to high" regret that was significantly associated with late symptom burden and multimodality treatment. Difficulty swallowing was the strongest driver of decisional regret.

Evaluation of the effect of a porcine reproductive and respiratory syndrome (PRRS) modified-live virus vaccine on sow reproductive performance in endemic PRRS farms

The efficacy of a porcine reproductive and respiratory syndrome (PRRS) modified-live virus vaccine in reproductive performance was evaluated under field conditions. Three PRRS endemic farms were selected based on their history of PRRS-associated reproductive failures. On each farm, a total of 40 sows were randomly allocated to either vaccinated (n=20) or unvaccinated (n=20) groups. Sows were vaccinated six weeks prior to breeding. Clinical data showed a significant improvement in reproductive performance in vaccinated sows. Sows in the vaccinated groups had a significantly (P<0.05) reduced number of stillborn piglets in all 3 farms. Sows in the vaccinated groups also had a significantly (P<0.05) higher number of live-born piglets in one of the farms. Sows in the vaccinated groups had a significantly (P<0.05) higher number of weaned piglets in two of the farms. Premature farrowing, one of the late gestation symptoms of PRRS, was also reduced due to vaccination as suggested by the increase in gestation length and the reduction in the number of stillborn piglets. No adverse systemic or local side effects relative to vaccination were observed during the entire gestation. No vaccine strain was detected in the vaccinated sows from all three farms at 70 and 114days post vaccination and in live-born piglets at the time of farrowing. Vaccination of sows with this PRRS vaccine was effective in improving reproductive performance in endemic PRRS farms.

Abstract 436: Folate cycle represents a new metabolic vulnerability for hepatocellular carcinoma treatment

Abstract Hepatocellular carcinoma (HCC), primary liver cancer, ranks the third most lethal cancer worldwide due to late symptom presentation and lack of promising curative therapy. Metabolic reprogramming has been recognized as a major and new hallmark of cancer in recent years. Better understanding of its underpinning molecular mechanisms favoring cancer growth will be crucial for the development of effective HCC therapeutics. The folate cycle fuels metabolic processes and the production of metabolites essential to cell growth and tumorigenesis maintenance. Through the shuttling of a single carbon unit by a folate derivative through the tetrahydrofolate (THF) backbone in the cytoplasmic and mitochondrial compartments, metabolites like NADPH - a major cellular antioxidant for redox balance, s-adenosyl methionine (SAM) - precursor of DNA and histone methylation, and pyrimidine and purine - the building blocks of DNA are produced. We found folate to be indispensable for HCC cell growth. Furthermore, methylene-THF dehydrogenase 1-like (MTHFD1L), a key enzyme facilitating the folate cycle from the mitochondria, was found to be significantly up-regulated in HCC with association to poorer clinical features for patients. Genetic inhibition of MTHFD1L by knockdown and knockout by shRNA and CRISPR-Cas9 systems, respectively, blocked NADPH production. Rapid elevation in oxidative stress induced DNA damage and cell cycle delay; ultimately inhibiting HCC proliferation. Binding of the transcription factor NRF2, a potent protector of oxidative stress, and MTHFD1L was confirmed by ChIP assay. NRF2 over-expression using the CRISPR-activating system in HCC cells further highlighted the dependent relationship between NRF2 and MTHFD1L. Metabolomics analysis showed that MTHFD1L knockdown caused a disruption to the folate cycle and accumulation of serine. Surprisingly, MTHFD1L knockdown did not reduce the levels of SAM and nucleotides. Knockdown of MTHFD1L in HCC cells significantly inhibited primary liver tumor growth and lung metastasis in orthotopic liver implantation model. Therapeutically, the administration of methotrexate, an anti-folate agent, sensitized HCC cells towards Sorafenib treatment both in vitro and vivo. The folate cycle represents a metabolic vulnerability and attractive therapeutic target for HCC. Inhibition of MTHFD1L disrupts the folate cycle and sensitizes HCC cells towards its convention treatment agent, Sorafenib in various HCC mouse models. Our investigation unravels a metabolic vulnerability in cancer which contributes to better understanding and is beneficial for the development of precise inhibitors specifically targeting associated pathways. Citation Format: Derek Lee, Iris Ming-Jing Xu, David Kung-Chun Chiu, Robin Kit-Ho Lai, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong. Folate cycle represents a new metabolic vulnerability for hepatocellular carcinoma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 436. doi:10.1158/1538-7445.AM2017-436

Milder clinical and biochemical phenotypes associated with the c.482G>A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening.

Cobalamin C disease is a multisystemic disease with variable manifestations and age of onset. Genotype-phenotype correlations are well-recognized in this disorder. Here, we present a large cohort of individuals with cobalamin C disease, several of whom are heterozygous for the c.482G>A pathogenic variant (p.Arg161Gln). We compared clinical characteristics of individuals with this pathogenic variant to those who do not have this variant. To our knowledge, this study represents the largest single cohort of individuals with the c.482G>A (p.Arg161Gln) pathogenic variant. A retrospective chart review of 27 individuals from 21 families with cobalamin C disease who are followed at our facility was conducted. 13 individuals (48%) are compound heterozygous with the c.482G>A (p.Arg161Gln) on one allele and a second pathogenic variant on the other allele. Individuals with the c.482G>A (p.Arg161Gln) pathogenic variant had later onset of symptoms and easier metabolic control. Moreover, they had milder biochemical abnormalities at presentation which likely contributed to the observation that 4 individuals (31%) in this group were missed by newborn screening. The c.482G>A (p.Arg161Gln) pathogenic variant is associated with milder disease. These individuals may not receive a timely diagnosis as they may not be identified on newborn screening or because of unrecognized, late onset symptoms. Despite the milder presentation, significant complications can occur, especially if treatment is delayed.

The Most Frequent Complications after Cranio-cerebral Injuries in Children Hospitalized at the Department of Paediatric Surgery

Introduction. Head injuries among children are the most frequent cause of hospitalization. Posttraumatic cranio-cerebral damage in children can lead to the occurrence of partial physical and mental disorders and in some cases prevent proper functioning of the organism.Aim. The goal of this research was to study the frequency of complication occurrence among children after cranio-cerebral traumas as well as to determine the character they most often take on.Material and Methods. The study was conducted at Paediatric Surgery Outpatient Clinic at the St. Luke District Hospital in Tarnów. It included 150 children hospitalized at the Department of Paediatric Surgery within the period from July to October 2015 due to sustained cranio-cerebral injuries ranging from minor and moderate to severe.Results. The most frequent causes of sustained injuries were sport-related ones as well as those resulting from a fall from height. Among the vast majority of the children with an injury (95%) an early posttraumatic complication occurred in the form of concussion. The most often demonstrated early side symptoms of sustained injury included: emesis (80%), poor well-being and headache (69%) as well as drowsiness and changes in behavior (53%). The most frequent late complication was posttraumatic cerebrasthenia characterized by headache, memory disorders and problems with concentration. In the study group of children with an injury, poor well-being and headache were experienced by approximately 50% of the patients one week following the hospital discharge and by approximately 20% one month after the discharge.Conclusions. The demonstrated early and late side symptoms observed among children with an injury, when properly treated and controlled, with time tend to decrease and thus contribute to comforting statistics of occurrence of a small number of serious complications following minor and moderate to severe cranio-cerebral injuries. (JNNN 2017;6(3):107–113)

Cases of acute mercury poisoning by mercury vapor exposure during the demolition of a fluorescent lamp factory

BackgroundIn 2015, workers dismantling a fluorescent lamp factory in Korea were affected by mercury poisoning from exposure to mercury vapor.Case presentationEighteen out of the 21 workers who participated in the demolition project presented with symptoms of poisoning and, of these, 10 had persistent symptoms even at 18 months after the initial exposure to mercury vapor. Early symptoms of 18 workers included a general skin rash, pruritus, myalgia, sleep disturbance, and cough and sputum production. Following alleviation of these initial symptoms, late symptoms, such as easy fatigue, insomnia, bad dreams, and anxiety disorder, began to manifest in 10 out of 18 patients. Seven workers underwent psychiatric care owing to sleep disturbance, anxiety disorder, and depression, and three workers underwent dermatologic treatment for hyperpigmentation, erythematous skin eruption, and chloracne-like skin lesions. Furthermore, three workers developed a coarse jerky movement, two had swan neck deformity of the fingers, and two received care at an anesthesiology clinic for paresthesia, such as burning sensation, cold sensation, and pain. Two workers underwent urologic treatment for dysfunction of the urologic system and impotence. However, symptomatic treatment did not result in satisfactory relief of these symptoms.ConclusionAwareness of the perils of mercury and prevention of mercury exposure are critical for preventing health hazards caused by mercury vapor. Chelation therapy should be performed promptly following mercury poisoning to minimize damage.

P-219 - Gemcitabine and nab-paclitaxel based regimen in advanced pancreatic carcinoma at tertiary cancer centre, Bangalore

Introduction: Pancreatic ductal adenocarcinoma is associated with the worst prognosis of all gastrointestinal malignancies, mainly due to late and nonspecific symptoms, an aggressive tumor biology, and resistance to most therapies. Only 10–20% of patients are resectable at presentation. For many of these remaining patients were subjected to systemic chemotherapy either to down stage in borderline resectable cases or to prolong the survival. Depending on the patient’s performance status and preferences, more or less aggressive regimens can be chosen. This study was to evaluate the efficacy and safety of Gemcitabine with Nab-paclitaxel regimen in advanced carcinoma of pancreas. Methods: We analyze the patients with ECOG performance status 0-2 in advanced pancreatic cancer who were treated with gemcitabine and Nab-Paclitaxel regimen from Jan2014 to April 2016 in our center. The patients those who failed to Folfirinox or Gemcitabine + Platinum based chemotherapy in first line setting were enrolled to receive gemcitabine and Nab-Paclitaxel regimen. The schedule of gemcitabine and Nab-Paclitaxel regimen was Gemcitabine 1000 mg/m2 and Nab-Paclitaxel 125mg/m2 on Day 1 and Day8 of each cycle every 3weeks. Primary prophylaxis with Growth factor support was given in age > 60 years. The efficacy and toxicity of above regimen were analyzed. Results: 37 patients with advanced Pancreas and good ECOG Performance status 0-2 were enrolled. The median age was 66 (range 48 to 75 years). Male: female ratio was 1.46:1. The tumor marker CA19-9 was elevated at baseline in 59.45% of patients. The efficacy of this regimen as follows Efficacy Gemcitabine and Nab-Paclitaxel regimen in First line therapy (n 16) versus Second line therapy (n 21) in advanced pancreatic cancer were shown in the following order: Complete response 6.25% vs 0), Partial response (31.25% vs 28.57%), Stable disease (37.5% vs 33.3%), Progressive disease (25% vs 38%), Median PFS in months (5.5 vs 3.5), Median OS in months(10.5m vs 8m) and 1 year survival (37.5% vs 23.8%) respectively. Tumor marker response (CA 19-9) >50% drop from baseline at 3 months was seen 40.9% of patients. Hematological toxicity: Anemia (27%), Neutropenia (37.8%), Febrile neutropenia (10.8%), Thrombocytopenia (29.7%). Nonhematological toxicity: Nausea/vomiting 18.9%, Diarrhea 21.6%, Peripheral neuropathy (27%), Mucositis 13.5%, Fatigue 37.8%, Median number of cycles completed by patients were 3 and dose reductions were required in 18.75% of first line and 33.3% in second line settings. Conclusion: Gemcitabine and Nab- Paclitaxel regimen is easily tolerable and efficacious regimen in both first and second line therapy of an advanced pancreatic cancer. The further studied are required to compare above regimen with Gemcitabine with platinum based combinations and to assess quality of life.

"Late" Withdrawal Syndrome after Carbamazepine In Utero Exposure in a CYP2C9 Slow Metabolizer Newborn.

We report a case of carbamazepine withdrawal syndrome following in utero exposure to carbamazepine related to a pharmacogenetic predisposition factor. The infant was born at 37 1/7 weeks’ gestation by cesarean section to a mother treated for epilepsy with carbamazepine. One hour and thirty minutes after birth, the infant presented a respiratory distress with severe oxygen desaturation requiring intubation 5 h after birth. On the third day of life the infant developed clinical signs of a withdrawal syndrome which resolved progressively after 16 days and symptomatic treatment. The infant genotype analysis showed two low activity CYP2C9 allelic variants (∗2/∗3 heterozygote) predicting a CYP2C9 slow metabolizer phenotype which could explain reduced carbamazepine elimination and a late and long-lasting withdrawal symptoms observed 3 days after birth. The association of a withdrawal syndrome with carbamazepine exposure has not been previously reported and pharmacogenetic tests might therefore be useful in identifying patients at risk.

Modern clinical and epidemiological characteristic of systemic lupus erythematosus based on the data of the territorial registry

Systemic lupus erythematosus (SLE) is a severe rheumatic disease characterized by polysymptomatic clinical picture. At the present stage, there are no updated epidemiological data due to the low prevalence of the disease. The aim of the study was to examine the current clinical and epidemiological characteristics of patients with systemic lupus erythematosus based on the information contained in the territorial register, analysis of occurrence and symptoms at the early stage of the disease. This study demonstrated the epidemiological and clinical characteristics of SLE from the analysis of 107 cases during the period from 2011 to 2013 and retrospective analysis of the cases for 1980-2013. The epidemiological situation was evaluated based on extensive and intensive indicators using statistical software license. The current SLE prevalence was estimated at 5,59 per 100 000 population in 2013, the incidence between 1994 and 2003 at 0,29 per 100 000 population and between 2004 and 2013 at 0,49, with the peak in 2010 up to 1,35 per 100 000 population. The average absolute growth and growth rate of SLE in the first decade was 0,05% and 0,24%, in the second decade 0,001% and 0,006% respectively, with the female to male ratio being 9:1, mean age of the patients 37,62±11,65 years), and ethnic composition of 87 Slavs and 15 Crimean Tatars. The most common symptoms at the early (polyarthritis, fever, dermatitis) and advanced (polyarthritis, Raynaud's syndrome, carditis, myalgia) stages differed from those specified by American College of Rheumatology (1997). The difference between early and late symptoms of SLE was documented . Based on the data obtained, the division of the disease into clinical subtypes (phenotypes) is proposed.

Long and Narrow Gastric Pouch versus Classic Globular Pouch in Laparoscopic Proximal Gastric Bypass: Effect on Weight Loss and Dumping Syndrome

Background: Laparoscopic proximal gastric bypass Roux-en-Y (LPGBRY) has been regarded for a long time as the gold standard treatment for morbid obesity and its comorbidities. With the presence of the newer strong options, like the gastric sleeve and the mini gastric bypass, refinements in technique are taking place to avoid its current problems. Early and late gastric dumping are known problems after proximal gastric bypass. Modifications in the technique by providing the patient with a long and narrow pouch might help the problem by slowing the gastric emptying time, also should it keep the weight loss in the acceptable range. Aim: The aim of this study is to evaluate whether constructing a long and narrow pouch can decrease the incidence of early and late dumping after laparoscopic proximal gastric bypass and to evaluate the likely impact of such a long and narrow pouch on the weight loss rates. Patients and methods: The study included 79 morbidly obese patients who received primary LPGBRY for treatment of their morbid obesity. They were divided into two groups; 42 patients who received LPGBRY with a long and narrow pouch (the [LN] group), and 37 patients who received LPGBRY with a classic globular pouch (the [G] group). Their 6 and 12 months’ percentage of excess weight loss (%EWL) were recorded. Also, one year after surgery, all patients were required to fill in an Arabic translation of the Sigstad dumping score questionnaire, followed one hour later by an Arabic translation of the Arts score symptoms of late dumping, only if they scored 7 or more. Results: No significant differences were found in the %EWL between both groups. In the Sigstad questionnaire, the most commonly recorded symptoms were the need to lie down and frequent eructation, followed by dizziness, and distension. Frequent eructation was significantly higher in the [LN] group, while dizziness and palpitation were significantly more common in the [G] group (p 0.05). Half the dumping patients in group [G] had late dumping symptoms. The incidence of late symptoms in the [G] group was significantly higher than in the long and narrow pouch [LN] group (p < 0.05). Conclusion: Long and narrow pouches in LPGBRY achieve similar weight loss rates as in the classic globular pouches. Constructing a long and narrow pouch produces similar overall dumping rate, but added significantly more eructation, less dizziness, less palpitation and less late dumping symptoms when compared to the classic globular pouches.

Expression profiles and function analysis of microRNAs in postovulatory aging mouse oocytes.

In this study, microRNA (miRNA) profiles in postovulatory aging mouse oocytes were analyzed by microarray screening and RT-qPCR. Hierarchical cluster analysis on the microarray data and KEGG pathway enrichment analysis on the mRNAs targeted by differentially expressed (DE) miRNAs between two adjacent egg-ages suggest that while only a mild alteration in miRNA expression occurred from 13 to 18 h, a great change took place from 18 to 24 h post hCG injection. Theoretical exploration on functions of the predicted target genes suggest that KEGG pathways enriched by 13-18 h DE miRNAs are correlated with early events of oocyte aging while pathways most enriched by 18-24 h or 24-30 h DE miRNAs are correlated with the late symptoms of aged oocytes. Experimental verification on functions of the key proteins predicted by the KEGG analysis and injection of miR-98 mimics or inhibitors further confirmed that miRNAs played stimulatory/inhibitory roles in postovulatory oocyte aging. In conclusion, marked changes in miRNA expression are associated with significant alterations in function and morphology of postovulatory aging oocytes.