DNA methylation in hepatocellular carcinoma

As for many other tumors,development of hepatocellular carcinoma(HCC)must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes,leading to activation of oncogenes and inactivation or loss of tumor suppressor genes(TSG).In the last decades,in addition to genetic alterations,epigenetic inactivation of(tumor suppressor) genes by promoter hypermet hylation has been recognized as an important and alternative mechanism in tumorigenesis.In HCC,aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

Early Morbidity and Perioperative Course of Neonates with Esophageal Atresia and Tracheoesophageal Fistula in a Tertiary Pediatric Surgical Center

Background: The management of infants (infs.) with esophageal atresia and tracheoesophageal fistula (EA ± TEF) is demanding and complex. The aim of this study was to evaluate early morbidity, the timing of surgery, and the results of surgery. Patients and Method: We collected data of 30 consecutive infs. treated for EA ± TEF between 2006 and 2014. Results: The median gestational age was 38 weeks (12 preterm), and the median Birth Weight (BW) was 2660 g (4 infs. had a BW 1500 g). The median Apgar score at 10 minutes was 10 (range 7 - 10). The median umbilical artery pH (UapH) was 7.30. According to the Spitz classification, 19 infs. were group 1, 9 infs. were group 2, and 2 infs. were group 3. Surgical repair was performed in 29 cases (25 EA;4 isolated TEF). Once the infs. arrived at the pediatric surgery department, surgery was postponed overnight in 11 cases. The duration of postoperative (p.o.) mechanical ventilation was significantly shorter for operations performed on day 2 after delivery. Twenty-four infs. (83%) underwent surgery within 2 days after delivery, and 5 infs. had later surgery. Chest drains (p.o.) for pneumothorax were inserted in 6 infs. (21%), and gastrostomy was performed in 6 cases (21%). No re-thoracotomy was required. The median length of hospital stay was 17.5 days (6 to 120). The incidence of p.o. mortality was 1 in 29 (3%). Discussion: The majority of the infs. presented growth retardation (indicated by low birth weight) and a stable immediate postnatal course. The data from this study support the concept of early but not emergent surgery for the majority of infs. with EA ± TEF. However, a remarkable rate of perioperative morbidity must be taken into account. Conclusion: Surgery for EA ± TEF can be performed safely during the first postnatal days with exception of very unstable preterm infants.

钙敏感受体基因突变:慢性胰腺炎新的遗传危险因素

Objective.In 2003 we identified a family with familial hypocalciuric hypercalcemia(FHH)(heterozygous CASR gene mutation L173P)and a mutation in the pancreatic secretory trypsin inhibitor gene(SPINK1)(N34S).While family members with an isolated calcium-sensing receptor gene(CASR)mutation remained healthy,a combination of the CASR and SPINK1 gene mutation caused chronic pancreatitis(CP).We thus speculate that the combination of two genetic defects affecting calcium homeostasis and pancreatic enzyme activation might represent a novel approach in chronic inherited pancreatic disease.We therefore sought to explore whether CASR gene mutations were prevalent in a cohort of patients with CP and confirmed SPINK1 mutations.Material and methods.A cohort of 19 families(n = 170)with a history of idiopathic CP(ICP)was screened for mutations within the CASR gene;104 members of that cohort had a mutation(N34S)within the SPINK1 gene and 66 of those were suffering from CP.The entire CASR gene was screened for single strand conformation polymorphism under varying polyacrylamide gel conditions and subjected to direct dideoxy nucleotide sequencing of amplified cDNA.Results.Single-strand conformation polymorphisms were observed in 59 samples,clustering of exons 3,4 and 7.DNA sequence analysis revealed a yet unreported missense mutation in exon 7(R896H)and two conservative mutations in exon 4(F391F)and exon 7(E790E).Furthermore,an intronic polymorphism in nucleotide position 493-19 G > A was detected in 19 out of 170 members of that cohort.Conclusions.We identified three novel calcium-sensing receptor gene mutations(1 missense mutation,2 silent mutations and 1 intronic polymorphism)in a cohort of 19 families with ICP.In particular,the kindred with the R896H mutation presenting with a similar pedigree to the family described above may indicate a role for CASR gene mutations in SPINK1-related CP.Again,only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis,whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected.We suggest that the CASR gene is a novel yet undetected co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.

Two-Phase Transplantation (TPTX) Concept: A New Approach for Instant Rehabilitation of Young Children after Avulsion of Central Incisor

Background: To present a new idea for rapid management of tooth avulsion in young children and adolescents (age: 6 to 16) by this case report. Case presentation: A nine-year-old boy presented with loss of upper permanent central incisor in early mixed dentition (6 to 10 years, phase I). The not yet fully resorbed primary canine was used as tooth transplant for the lost incisor. The intentional renounce on endodontic treatment of the primary transplant permits natural exfoliation of the transplant occurring either spontaneously or due to undermining resorption through the adjacent erupting teeth. In the late mixed dentition (10 to 16 years, phase II), the primary tooth transplant is electively removed and replaced by a premolar autotransplant for long-term rehabilitation of the meanwhile adolescent patient. Results: Primary canine autoTX acts as a temporary denture with instant surgical gap closure. Ensuing premolar autoTX in phase II then acts as permanent denture with excellent 10 years survival rates. Patient satisfaction issued by a questionnaire resulted in good to very good school grades for both phases of autotransplantation. Conclusions: The “TPTX” concept is a new surgical approach that immediately restores the patient’s function and aesthetics after tooth loss in early childhood supporting the growth of local bone and soft tissue in the growing adolescent jaw.

Emergency Surgical Intervention by Mobile Surgical Team in the NICU

The objective of this study was to describe our NICU’s (neonatal intensive care unit) experience with mobile surgical team and to demonstrate its effectiveness. Method: We analyzed the data of 17 consecutive very low birth weight and extremely low birth weight infants over 3 years who underwent 22 procedures (19 emergency and 3 elective). The gestational age at birth was a median of 25 weeks (range 24 - 39), and the median birth weight was 613 g (range from 340 g to 1100 g). The infants received their operations during their first 2 weeks of life (median 7 days, range from 1 to 14). Results: The spectrum of primary surgical diagnoses included spontaneous intestinal perforations (n = 8), gastric perforations (n = 3), necrotizing enterocolitis (n = 2), meconium ileus (n = 2), and miscellaneous (n = 2). An emergency laparotomy with either a bowel or a gastric procedure was performed in 16 cases. Postoperatively, all infants required mechanical ventilation from 1 to 43 days (median 6.5 days). Complications included a metachronous small bowel perforation, an ileostomy retraction, a prolapsed stoma, and impaired wound healing;we had one postoperative death. Two infants died later in the NICU (mortality 3 of 16;19%). Conclusion: Off-site surgery for preterm infants in the NICU is feasible. This approach prevents the risks of transportation, and parents and neonatologists alike feel comfortable with this regimen. However, biases may exist regarding the surgeon’s decision to operate, the choice of procedure, and the follow-up.

Pyloric Stenosis and Nonbilious Vomiting in Infants: Negative Base Excess and Hypercapnia—Two Opposing Points of One Scale a Comparative Case Series

Background: Blood pH and bicarbonate estimations are basal acid-base laboratory tests that are performed in infants with infantile hypertrophic pyloric stenosis (IHPS). This study aimed to define the clinical value of pCO2 and BE in infants suspected to have IHPS. Methods: We collected data from 80 “surgical” infants younger than 100 days with prolonged nonbilious vomiting who were suspected to have IHPS. In 65 infants, pyloric stenosis was confirmed, and 15 infants had nonsurgical conditions. Capillary blood was tested for standard acid-base parameters and lactate. The two groups were compared. Results: Eighty-eight percent of the IHPS infants had elevated standard bicarbonate levels (st bicarb) > 25 mmol/l, and 60% had BE > 3.5 mmol/l;12% of the infants showed hypercapnia (pCO2 ≥ 50 mmHg) associated with markedly increased standard bicarbonate and BE. Infants with nonsurgical vomiting were older at admission (p = 0.002), had a longer duration of vomiting (p < 0.001), were older (p = 0.002) and weighted more at admission (p = 0.004), had lower pCO2 (p = 0.021), lower st bicarb (p < 0.001) and lower BE (p = 0.001). In addition, nonsurgical infants showed a trend to anemia (p = 0.002). Conclusions: In infants with IHPS/nonbilious vomiting, acid-base analysis (ABA) is equivocal or inconclusive. These findings may be misleading and could result in a false clinical decision. Nonsurgical vomiting is associated with a lower degree of alkalosis, normocapnia to slight hypercapnia and a base deficit. However, even infants with IHPS may present with a negative BE. In infants with IHPS and severe alkalosis, hypercapnia carries a risk for respiratory depression. Monitoring the infant’s respiration allows for the early detection of respiratory deterioration.

Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome

Coronavirus disease 2019(COVID-19)related acute respiratory distress syndrome(ARDS)is a severe complication of infection with severe acute respiratory syndrome coronavirus 2,and the primary cause of death in the current pandemic.Critically ill patients often undergo extracorporeal membrane oxygenation(ECMO)therapy as the last resort over an extended period.ECMO therapy requires sedation of the patient,which is usually achieved by intravenous administration of sedatives.The shortage of intravenous sedative drugs due to the ongoing pandemic,and attempts to improve treatment outcome for COVID-19 patients,drove the application of inhaled sedation as a promising alternative for sedation during ECMO therapy.Administration of volatile anesthetics requires an appropriate delivery.Commercially available ones are the anesthetic gas reflection systems AnaConDa®and MIRUSTM,and each should be combined with a gas scavenging system.In this review,we describe respiratory management in COVID-19 patients and the procedures for inhaled sedation during ECMO therapy of COVID-19 related ARDS.We focus particularly on the technical details of administration of volatile anesthetics.Furthermore,we describe the advantages of inhaled sedation and volatile anesthetics,and we discuss the limitations as well as the requirements for safe application in the clinical setting.

人类丘脑在处理伴随放电中的作用

Corollary discharge signals play an important role in monitoring self-generat ed movements to guarantee spatial constancy. Recent work in macaques suggests th at the thalamus conveys corollary discharge information of upcoming saccades pas sing from the superior colliculus to the frontal eye field. The present study ai med to investigate the involvement of the thalamus in humans by assessing the ef fect of thalamic lesions on the processing of corollary discharge information. T hirteen patiente with selective thalamic lesions and 13 healthy age-matched con trol subjects performed a saccadic double-step task in which reiino-spatial di ssonance was induced, i.e. the retinal vector of the second target and the movem ent vector of the second saccade were different. Thus, the subjects could not re ly on retinal information alone, but had to use corollary discharge information to correctly perform the s econd saccade. The amplitudes of first and second saccades were significantly sm aller to patients than in controls. Five thalamic lesion patients showed unilate ral deficits in using corollary discharge information, as revealed by asymmetrie s compared with the other patients and controls. Three patients with lateral tha lamic lesions including the ventrolateral nucleus (VL) were impaired contralater ally to the side of damage and one patient with a lesion in the mediodorsal thal amus (MD) was impaired ipsilaterally to the lesion. The largest asymmetry was fo und in a patient with a bilateral thalamic lesion. The results provide evidence for a thalamic involvement in the processing of corollary discharge information to humans, with a potential role of both the VL and MD nuclei.

Endoscopic Detection and Surgical Repair of Congenital Tracheo-Esophageal-Fistula(TEF)±Esophageal Atresia(EA)

Purpose: This study was performed to evaluate the management of tracheoesophageal fistula (TEF) ± esophageal atresia (EA) under the guidance of preoperative tracheo-bronchoscopy (TrSc). Methods: Between 2007 and July 2014, a total of 26 consecutive newborns who underwent rigid TrSc for suspected TEF were identified. All associated charts and operation reports were retrospectively analyzed. Results: Distal TEF with EA (Gross C) predominated (n = 18). Furthermore, we managed 2 infants with proximal and distal TEF (Gross D) and 4 infants with isolated TEF (Gross E). In our hands, TrSc was feasible in infants with a birth weight above 1300 g. Twenty-five fistulas were identified by endoscopy in 23 patients. In one infant with a birth weight below 1000 g, an attempt to perform TrSc was interrupted, and urgent TEF closure was required. Fistula site at the carina was associated with a high rate of esophageal anastomosis under tension. During surgery, proximal TEF and isolated TEF were safely approached via right cervicotomy (n =5). Conclusion: This study supports the routine use of rigid TrSc at the time of surgery. Rigid TrSc allowed the surgical team to identify the number and location of TEFs, and the incidence of side effects was low.

“Inverse Type” Apple-Peel Syndrome Is Associated with Type III Colonic Atresia in a Neonate with Gastroschisis—A “New” Subtype of Colonic Atresia

The colon is an unusual site of intestinal atresia. Colonic atresia is subdivided into three phenotypes. Type III is the most common phenotype, where the proximal and distal blind sacs are not connected. Here, we report on the presence of colonic atresia with an “inverse apple-peel” appearance in a neonate with gastroschisis. The lack of mesenteric fixation of the entire small intestine, including the proximal colon, and the twisting around the vascular axis of the superior mesenteric artery led to intrauterine volvulus and hemorrhagic infarction of the ileocolic bowel at 34 weeks of gestation. According to the current nomenclature for small bowel atresia, we introduce type IIIB into the current colonic atresia classification. The occurrence of type IIIB has been mentioned in the literature, but no single cases have been reported until now. Patients with this type of atresia are predisposed to the loss of the ileocecal region.

Adnexal Sliding Hernia in an Infant: Clinical-Anatomical Case Report

We present a case report of laparoscopic herniorrhaphy in an infant with ovarian prolapse. Using this case study, we demonstrate the role of the ovarian ligamentous apparatus. A structure appearing like the male gubernaculum was identified. The anatomical and functional role of this “gubernaculum” will be the subject of discussion. Further detailed laparoscopic examinations are indicated to better understand the ligamentous anatomy of ovarian prolapse.