Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Peripartum cardiomyopathy--a case report.

Peripartum cardiomyopathy in the form of congestive heart disease of unknown etiology appears relatively rarely during the last month of pregnancy or within 5 months after delivery, and it is potentially life-threatening. This case report describes a 34-year-old female, G4P1, at 36 weeks' gestation who was admitted for cesarean section under lumbar epidural anesthesia due to twin pregnancy. She had no past history of cardiovascular diseases. However, rapid onset of dyspnea at ward and acute cardiac failure developed 15 h after cesarean section. Peripartum cardiomyopathy was diagnosed. After a 7-day intensive treatment she was discharged. Since then she was symptom-free and her two babies were doing well during a period of one more years after discharge.

[Another reason for cyanosis--methemoglobinemia].

Intraoperative cyanosis is an utmost emergency for anesthesiologist. If the patient has adequate control ventilation, and normal cardiac pulmonary physiology, then methemoglobinemia must be considered. Reported here is a normal female with dark color lip on the second day after her second parturition and was undergoing tubal ligation. Twenty minutes after induction of general anesthesia and endotracheal intubation, dark blood at the incision site was noted by the operator. After emergent check up of the anesthesia machine, tubings, breathing sound and arterial blood gas, there was only one suspicion left. Methemoglobinemia was confirmed by the hematological examination. Methemoglobinemia is a product from the oxidation of the iron atom in the heme ring when oxygen dissociates from it. This process exists in nature, but can also be induced by nitrate or nitrite-containing drugs or foods or benzene-like organic compounds. Methemoglobinemia can be differentiated from normal hemoglobin by mass spectrometry. If acute illness develops, patients should be treated with methylene blue. Otherwise ascorbic acid will do. This case is reported to remind all anesthesia personnel about one of the rare but serious hemoglobinopathy.

Epidural anesthesia for emergency caesarean section in a patient with single ventricle and aortic stenosis.

A 24-year-old parturient with single ventricle and moderate aortic stenosis was admitted due to preeclampsia and fetal distress at 31 weeks' gestation. Emergency Caesarean section was performed under lumbar epidural anesthesia and epidural analgesia was given for post-operative pain control. Mother and baby both survived. The anesthetic techniques and managements in other parturients with similar congenital cardiac anomalies are also reviewed and described.

[Ilioinguinal nerve blockade with or without epinephrine for analgesia after caesarean section].

The analgesic effect of bilateral ilioinguinal nerve blockade with or without epinephrine after caesarean section with Pfannenstiel incision was investigated in 36 ASA class 1-2 parturients. They were randomly classified into 3 groups of 12 each. Before the patients were extubated from standard general anesthesia, bilateral ilioinguinal nerve blockade was performed. Group A patients were the control group. Group B patients received 0.375% plain marcaine 10 mL to each side. Group C patients received 0.375% plain marcaine with 1:200000 epinephrine 10 mL to each side. The pain scores and requirement for post operative analgesia of group B and C were compared with the control group A. The pain scores of group B and C were decreased 30% and 37% respectively during the first eight hours after operation. However, group C patients had lower pain scores during the first day after operation. There was an increased time from anesthesia to the first injection of pethidine in group B and C when compared with group A (4.57 +/- 2.94, 4.38 +/- 2.72 and 1.8 +/- 0.9 hr, respectively). However, no significant difference between group B and C. The total pethidine requirement were decreased in group B and C although the mean pethidine dose was not statistically significant. The results suggest that bilateral ilioinguinal nerve blockade improve the quality of postoperative analgesia. The adding epinephrine can prolong the duration of nerve blockade.

The evaluation of subarachnoid administration of fentanyl for surgery and postoperative analgesia in patients undergoing cesarean section.

The use of spinal opioids for postoperative analgesia has gained popularity in recent years. In this study, subarachnoid fentanyl 20 micrograms was evaluated to determine its efficacy for postoperative analgesia, its possible side effects and its effects on the newborn. Sixty ASA class I or II at-term parturients undergoing elective cesarean section were randomly divided into two groups. In one group fentanyl 20 micrograms (0.4 ml) with 0.5% heavy marcaine 2.0 ml was given intrathecally and in the other group only 0.5% heavy marcaine 2.0 ml with CSF 0.4 ml was given intrathecally. The average time for patients in the fentanyl group to demand the first dose of narcotic for pain was 6.8 +/- 3.2 h and in the control group it was 3.9 +/- 1.1 h. The incidences of postoperative nausea and vomiting were higher in the fentanyl group than in the control group. Pruritus was only found in the fentanyl group and amounted to 50%. Early or late respiratory depression was not found in the fentanyl group. During operation, all patients were wakeful and alert. Neonatal condition as determined by 1-min and 5-min Apgar score was satisfactory and showed no significant difference in both groups. Examination on neurobehavior and reflexes done at the baby room showed no abnormality in both groups.

Lumbar extradural morphine and caudal extradural morphine for postoperative analgesia and their adverse effects.

The efficacy of morphine by either lumbar extradural route or caudal extradural route and their adverse effects for postoperative analgesia were studied by comparing with the control group without morphine administration. 105 patients, 79 males and 26 females, aged 18 to 70 years, scheduled for hemorrhoidectomy surgery were selected. They were randomly assigned into three groups, i.e group I: without morphine use as control group (n = 35), group II: lumbar extradural morphine group (n = 35) and group III: caudal extradural morphine group (n = 35). Patients in group I received general anesthesia by face mask after induction by intravenous anesthetics and maintained with potent halogenated inhalation agents (isoflurane) through face mask. Patients in group II received lumbar extradural blockade through the L4-L5 intervertebral space, and those in group III received caudal extradural blockade through the sacrococcygeal junction (sacral hiatus) for intraoperative anesthesia and analgesia. Drugs included 0.5% bupivacaine 10ml + 2% xylocaine 10ml + 2mg morphine HCl + 0.1mg epinephrine were given either into the lumbar extradural space or into the caudal extradural space. No more narcotic has been given throughout the whole intraoperative course. All of these patients were followed up 24 hours later after the end of anesthesia. There were 11 patients (31.4%) in the control group, 26 patients (74.3%) in the lumbar extradural morphine group, and 25 patients (71.4%) in the caudal extradural morphine group who did not need additional narcotic for pain relief for more than 24 hours postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrathecal morphine's effect on somatosensory impulses transmission-studied with posterior tibial nerve SSEP.

In order to investigate neurotoxic potential of spinally injected morphine solution, somatosensory evoked potential (SSEP) was utilized to detect the change of electrophysiologic activity of spinal neurons after long term application of intrathecal morphine. Eight patients received intrathecal morphine injection regularly after CHEMO-PORT implantation were studied with posterior tibial nerve SSEP. Patients received SSEP examination just before and right after first episode of morphine injection and were followed up at 30 minutes, 60 minutes, 2 hours, 8 hours, and the 7th day and the third month of regularly injection. The results showed that there were no definite change of latencies and amplitudes of impulses generated by lumbar spinal cord (N22) and cortex (P40). We therefore suggest that electrophysiologic activities of spinal cord and cortex are not affected by chronic intrathecal morphine injection. Possible mechanism and proposed pathway of morphine's action were also discussed.

Combined epidural lidocaine-fentanyl-epinephrine for cesarean section.

The combined use of fentanyl-epinephrine-lidocaine in epidural analgesia was investigated in 60 mothers who underwent elective Cesarean section. They were randomly classified into 4 groups of 15 each. Group A received 20 mL of 2% lidocaine 3 mL normal saline. Group B received 20 mL of 2% lidocaine with freshly added 1:200000 epinephrine and 5 mL normal saline. Group C received 20 mL of 2% lidocaine and 2 mL of fentanyl in 3 mL normal saline. Group D received 20 mL of 2% lidocaine and 5 mL normal saline. The duration of action was nearly doubled in the groups with epinephrine added. The quality of the analgesia was assessed by the degree of intraoperative analgesia; 93% of the patients in group A were classified as "Excellent"; while only 67% in group B were classified as "Excellent". The difference in patient's acceptance was statistically significant. 93% vs 27% in Group A and Group C; 67% vs 6.7% in Group B and Group D rated "Excellent". The results suggest that both fentanyl and epinephrine improve intraoperative analgesia. Epinephrine offers a greater analgesic effect than fentanyl.

Neonatal status in cesarean section under epidural anesthesia with supplementary oxygen.

Simple O2 mask has been used in patient under regional anesthesia for increasing the FiO2, especially in the aged and the pregnant. The relationships between maternal FiO2 and umbilical arterial (UA) and venous (UV) PO2, PCO2, pH, and neonatal Apgar score were studied in 45 patients receiving Cesarean section under epidural anesthesia. 2% xylocaine 18-20 ml with adrenaline 1:200,000 was used to attain the sensory level of T-4. Patients were allocated randomly into three groups. Group I, acting as a control group, breath only room air during the course of anesthesia. Group II was breathing through a simple face mask with an oxygen inflow of 6L/min. Group III was breathing oxygen with a flow rate of 10L/min through a simple face mask. UA and UV blood samples were collected separately at the time of delivery for blood gas analysis. The 1-min, and 5-min Apgar scores were recorded also. Mean values of the UA blood samples for the 3 groups (Gp. I, Gp. II and Gp. III respectively) were: PO2--16.50 mmHg, 20.20 mmHg and 19.50 mmHg; PCO2--49.20 mmHg, 48.10 mmHg and 50.3 mmHg; pH--7.31, 7.30 and 7.30. Mean values of the UV blood samples for the 3 groups (Gp. I, Gp. II and Gp. III respectively) were: PO2--28.6 mmHg, 36.9 mmHg and 36.5 mmHg; PCO2--38.20 mmHg, 38.80 mmHg and 40.40 mmHg; pH--7.36, 7.36 and 7.34. There was a significant increase in UA and UV PO2 when using a simple O2 mask (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)