Prolonged extracorporeal membrane oxygenation support for acute respiratory distress syndrome.

When all conventional treatments for respiratory failure in patients with acute respiratory distress syndrome (ARDS) have failed, extracorporeal membrane oxygenation (ECMO) can provide a chance of survival in these desperately ill patients. A 49-year-old male patient developed septic shock and progressive ARDS after liver abscess drainage. Venovenous ECMO was given due to refractory respiratory failure on postoperative day 6. Initially, two heparin-binding hollow-fiber microporous membrane oxygenators in parallel were used in the ECMO circuit. Twenty-two oxygenators were changed in the first 22 days of ECMO support because of plasma leak in the oxygenators. Each oxygenator had an average life of 48 hours. Thereafter, a single silicone membrane oxygenator was used in the ECMO circuit, which did not require change during the remaining 596 hours of ECMO. The patient's tidal volume was only 90 mL in the nadir and less than 300 mL for 26 days during the ECMO course. The patient required ECMO support for 48 days and survived despite complications, including septic shock, ARDS, acute renal failure, drug-induced leukopenia, and multiple internal bleeding. This patient received an unusually long duration of ECMO support. However, he survived, recovered well, and was in New York Heart Association functional class I-II, with a forced expiratory volume in 1 second of 81% of the predicted level 18 months later. In conclusion, ECMO can provide a chance of survival for patients with refractory ARDS. The reversibility of lung function is possible in ARDS patients regardless of the severity of lung dysfunction at the time of treatment.     

Dome-shaped high tibial osteotomy: a long-term follow-up study.

BACKGROUND: High tibial osteotomy (HTO) is a well-established treatment for unicompartmental gonarthrosis of the knee, but its durability and complications remain controversial. We previously introduced a novel dome-shaped HTO, and the long-term follow-up results using this technique are analyzed in this study. METHODS: We treated 25 varus knees in 22 patients with medial gonarthrosis, using a specially designed calibrated cutting jig along with rigid external fixation and early joint motion postoperatively. A total of 16 patients (19 knees) completed the study protocol and were followed up for 13-16 years (mean, 15 years). RESULTS: The surgery attempted to obtain 8 degrees valgus; the actual postoperative alignment averaged 12.4 degrees valgus, which decreased significantly to 7.8 degrees valgus after 5 years. The outcome as assessed by the Hospital for Special Surgery knee score was excellent or good in 18 knees at 5 years postoperatively, and in 13 knees at the final follow-up, showing a significant deterioration with time. Loss of correction with time was not correlated with the postoperative alignment achieved: at 5 years, loss greater than 2 degrees was found in 12 knees, but their mean corrected angle (11.8 degrees valgus) was not significantly different from that of the others (13.3 degrees valgus). Nor was the loss of correction correlated with the knee scores. The mean amount of joint motion after surgery did not change significantly with time: 124 degrees preoperatively and 114 degrees at the final follow-up. The patellar position also did not change from preoperative values during postoperative follow-up: mean Insall-Salvati index was 0.88 before and 0.90 5 years after surgery, neither showing patella baja. CONCLUSION: Dome-shaped HTO is a durable time-buying procedure for patients with unicompartmental medial gonarthrosis, and can avoid subsequent development of patella baja that may complicate further prosthetic arthroplasty.     

Validation of a computer-based bronchoscopy simulator developed in Taiwan.

BACKGROUND/PURPOSE: Conventional training in bronchoscopy may increase patient's discomfort and procedure-related morbidity. Computer-based bronchoscopy simulator (CBBS) permits the acquisition and evaluation of the necessary skills through a realistic bronchoscopic experience. This study was conducted to validate the use of a CBBS system developed in Taiwan as a learning and assessment tool. METHODS: Twenty novice bronchoscopists and 10 expert bronchoscopists were enrolled as subjects in this prospective study. The 20 novice bronchoscopists were randomized into two groups, which received conventional bronchoscopic training or CBBS training and then completed a satisfaction survey. Subsequently, the novices who received CBBS training underwent an observational performance trial and the results were compared with those of expert bronchoscopists. All 10 expert bronchoscopists completed a realism survey and observational trial after CBBS performance. RESULTS: The satisfaction survey showed that the CBBS training program significantly increased participants' satisfaction (p = 0.002) and interest in learning (p < 0.001). The realism survey by the 10 expert bronchoscopists indicated that CBBS provides a favorable degree of realism with regard to the mechanical and visual parameters examined. Analysis of the performance results showed that the following parameters were capable of differentiating the participants by level of expertise: total procedure time (p = 0.002), percentage of bronchial segments entered (p = 0.012), percentage of bronchial segments identified (p < 0.001), percentage of repeated bronchial segments entered (p = 0.004), percentage of pathologies identified (p < 0.001), number of times that the bronchoscope tip collided with airway walls (p = 0.013), and number of times oral instruction was needed (p = 0.01). CONCLUSION: CBBS is a valid training method that increases interest in learning and provides a favorable degree of virtual realism. It can also distinguish various levels of competence at actual bronchoscopy and may have a useful role in the bronchoscopic training curriculum.     

Spinal pseudoarthrosis: a rare complication in psoriatic arthritis.

Discovertebral erosion with pseudoarthrosis is a well-known complication in ankylosing spondylitis but it is seldom mentioned in psoriatic arthritis. We report a 53-year-old woman with an 8-year history of psoriatic arthritis who developed severe low back pain followed by sudden onset of numbness in the lower limbs, weakness and dysesthesia. Abnormal contour of L1 and L2 vertebrae and intervertebral disc space was noted during radiologic examination. Pseudoarthrosis was suspected based on extensive osseous resorption and reactive sclerosis about the discovertebral junction on magnetic resonance imaging study. She underwent emergency operation due to spinal instability with neurologic deficit. Pseudoarthrosis was confirmed intraoperatively. No evidence of infection or neoplasms was found. This case shows that pseudoarthrosis can be complicated in patients with psoriatic arthritis, and this possibility should be considered in patients with previously quiescent disease.     

Emergency peripartum hysterectomy in a teaching hospital in Eastern Taiwan.

This study aims to review the incidence, indications, risk factors and complications associated with emergency peripartum hysterectomy in a teaching hospital. We reviewed records of patients undertaking emergency peripartum hysterectomy performed at our institution from 1998 to 2004. Emergency peripartum hysterectomy was defined as one performed for haemorrhage unresponsive to other treatments <24 h after delivery. Eight cases of emergency peripartum hysterectomy were performed. The rate of peripartum hysterectomy was 0.25%. The main indications for hysterectomy were uterine atony and abnormal placentation. No maternal death occurred. Use of peripartum hysterectomy may become necessary in managing obstetrical haemorrhage refractory to other measures.     

The antiproliferative activity of prodelphinidin B-2 3'-O-gallate from green tea leaf is through cell cycle arrest and Fas-mediated apoptotic pathway in A549 cells.

Prodelphinidin B-2 3'-O-gallate, a proanthocyanidin gallate isolated from green tea leaf, was investigated for its anti-proliferative activity in human non-small cell lung cancer A549 cells. The results showed that prodelphinidin B-2 3'-O-gallate inhibited the proliferation of A549 cells with no detectable toxic effects on normal WI-38 cells as measured by the XTT assay. Flow cytometric analysis showed that prodelphinidin B-2 3'-O-gallate blocked cell cycle progression in the G0/G1 phase. In addition, prodelphinidin B-2 3'-O-gallate effectively induced A549 cell apoptosis as determined by assessing the nucleosome level in cytoplasm. Enzyme-linked immunosorbent assay showed that the G0/G1 phase arrest is due to p53-independent induction of p21/WAF1. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by prodelphinidin B-2 3'-O-gallate. We suggested that prodelphinidin B-2 3'-O-gallate's activities might be potentially contribute to its overall chemopreventive effects against lung cancer, and can possibly be considered for future therapeutic application.     

Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer.

PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.     

Solitary fibrous tumors of the pleura: clinical, radiological, surgical and pathological evaluation.

AIMS: To report a clinicopathological series of cases of solitary fibrous tumor of the pleura from Taiwan. METHODS: Clinical data was collected from a review of medical records and telephone interviewing for follow-up. RESULTS: Eight patients, three men and five women aging from 34 to 71 years, underwent tumor resection and were followed in a period from 7 months to 13.5 years. Six patients underwent standard thoracotomy and two had VATS for tumor excision. Tumors were pathologically benign in seven patients and malignant in one. Patients were all alive with no evidence of tumor recurrence at the time of this report. CONCLUSIONS: One should always consider SFTPs as potentially malignant tumors. Complete resection remains the mainstay of cure. Standard thoracotomy should always be considered when a high suspicion of malignancy is raised, whereas VATS may be a preferred approach for smaller tumors.     

Classification and treatment of pooling of contrast material on computed tomographic scan of blunt hepatic trauma

BACKGROUND: Pooling of contrast material on computed tomographic (CT) scan represents free extravasation of blood as a result of active bleeding. For patients with blunt hepatic injury, aggressive management such as angiography or celiotomy is usually indicated if this sign is detected. The purposes of this study were to further categorize this CT scan finding and to correlate its characteristics with clinical outcomes. This CT scan classification might be helpful for the selection of appropriate management. METHODS: During a 42-month period, 276 patients with blunt hepatic injury were treated. Two hundred twelve of them were hemodynamically stable after initial resuscitation and underwent abdominal CT scan examination. Pooling of contrast material was detected on the CT scans of 15 patients. The CT scans and medical records were reviewed. Special attention was paid to the presence, location, and character of the extravasated contrast material. RESULTS: The finding of pooling of contrast material on CT scan was categorized into three types according to its location and character. Type I showed extravasation and pooling of contrast material in the peritoneal cavity (six patients). All patients with type I CT scan findings became hemodynamically unstable soon after CT scan examination and required emergent laparotomy. Type II findings showed simultaneous presence of hemoperitoneum and intraparenchymal contrast material pooling (six patients). Four patients with type II CT scan findings required laparotomy for hemostasis. Type III findings showed intraparenchymal contrast material pooling without hemoperitoneum (three patients). All patients with type III CT scan signs remained hemodynamically stable. CONCLUSION: With the use of a high-speed spiral CT scanner, it is possible to predict the necessity of operative management or angiography for patients with blunt hepatic injury before deterioration of hemodynamic status. The presence of pooling of contrast material within the peritoneal cavity indicates active and massive bleeding. Patients with this CT scan finding show rapid deterioration of hemodynamic status. Most of these patients might require emergent surgery. Pooling of contrast material in a ruptured hepatic parenchyma indicates active bleeding. Close monitoring and emergent angiography should be performed. Deterioration of hemodynamic status in these patients usually requires prompt surgical intervention. Intraparenchymal pooling of contrast material with unruptured liver capsule often indicates a self-limited hemorrhage. Patients with this CT scan finding have a high possibility of successful nonoperative treatment.     

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.