Intrathoracic Cavity Research Articles

ED15.03 Surgery of Thymic Malignancies

ED15.03 Surgery of Thymic Malignancies

ISY-11-3 - Development of RNAi-based anticancer drug: What is problem for clinical application and how establish a useful RNAi drug

During about two decades, a number of therapeutic drugs focused to RNA interference (RNAi) have been developed, however these drugs have been still unsuccessful due to various problems such as targeted disease, drug delivery system, dosing route, stability in the body and so on. To resolve these problems, we focused to develop new drug delivery system using cationic liposome and short-hairpin RNAi molecule for thymidylate synthase (TS shRNA), an important rate-limiting enzyme of DNA biosynthesis in cancer. To avoid a rapid degradation in the blood and immunological incidence of TS shRNA conjugated with liposome (named as DFP-10825), intraperitoneal and/or intrathoracic administration of DFP-10825 were applied to evaluate the antitumor activity on disseminated ascetic ovarian, gastric and pancreatic cancer models and/or malignant mesothelioma xenografts implanted into intrathoracic cavity. Locally injected DFP-10825 resulted in potent antitumor activity and prolonged survival on these cancer models with relative long-time retention of DFP-10825 in the cavity. In addition, the combination of DFP-10825 (i.p.) and paclitaxel (i.p.), down-regulator of TS, or pemetrexed (i.p.), one of TS inhibitors, showed augmented antitumor efficacy and further prolonged survival in those cancer models. DFP-10825 is a stable freeze-dried preparation and capable of being prepared in a large amount at once. Our novel trial for RNAi-based anticancer therapy will have a clinical benefit to treat patients with disseminated peritoneal cancers. We cooperate with a biotechnology venture company, Delta-Fly Pharma and plan to enter a clinical trial within 1.5 years.

Utility of GATA3, mammaglobin, GCDFP-15, and ER in the detection of intrathoracic metastatic breast carcinoma

Breast carcinoma (BC) metastatic to the intrathoracic cavity is difficult to diagnose due to low sensitivity of current immunohistochemical (IHC) stains. Mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15), and estrogen receptor (ER) immunomarkers show variable results. GATA3 is a recently described marker for detecting urothelial and breast cancers. Our goal is to test the utility of GATA3 in cell blocks from thoracic cytology specimens. We retrieved cases of BC that metastasized to the thoracic cavity from January 1, 2005 to September 30, 2013. IHC was performed on the cell blocks for the presence of GATA3, ER, GCDFP-15, and mammaglobin. Stains were scored quantitatively and qualitatively. Fifty cases of metastatic BC found in pleural effusions and endobronchial ultrasound-guided fine-needle aspirates were identified in 48 patients. Thirty-four cases had sufficient material for IHC (19 pleural effusions, 15 endobronchial ultrasound-guided fine-needle aspirates). GATA3 showed strong nuclear positivity in 31 of 34 cases (91.2%). ER (25 of 34, 73.5%), mammaglobin (23 of 34, 67.6%) and GCDFP-15 (11 of 34, 32.6%) were positive in fewer cases. GATA3 and ER were concordant in 26 of 34 cases (76.5%) (24 ER/GATA3-positive, 2 ER/GATA3-negative). Discordant results were found in 8 of 34 cases (23.5%). Of these, GATA3 was positive and ER was negative in 7 cases. GATA3 was negative and ER was positive in 1 case. GATA3 is more sensitive than ER, mammaglobin, or GCDFP-15 in detecting metastatic BC in cytologic specimens. GATA3 may be positive when ER is negative. In cytologic specimens with limited diagnostic material, GATA3 may be used as a first-line marker in a limited IHC panel to support metastatic BC.

Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.

Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors.

A Large Intra-Abdominal Hiatal Hernia as a Rare Cause of Dyspnea

Giant hiatal hernias, generally seen at advanced ages, can rarely cause cardiac symptoms such as dyspnea and chest pain. Here, we aimed to present a case with a large hiatal hernia that largely protruded to intrathoracic cavity and caused dyspnea, particularly at postprandial period, by compressing the left atrium and right pulmonary vein. We considered presenting this case as large hiatal hernia is a rare, intra-abdominal cause of dyspnea.

Severe hemodynamic deterioration caused by cardiac herniation during endoscopic thoracic sympathicotomy in a patient with previously undiagnosed congenital pericardial defect.

Severe hemodynamic deterioration caused by cardiac herniation during endoscopic thoracic sympathicotomy in a patient with previously undiagnosed congenital pericardial defect.

Thoracic empyema due to migrated endoclips after laparoscopic cholecystectomy

We describe the case of a patient who developed right thoracic empyema 1 year after laparoscopic cholecystectomy. The patient experienced right chest pain and swelling; radiography and CT showed an intrathoracic abscess penetrating the extrathoracic space and the presence of metal clips over the diaphragm. After drainage of the subcutaneous abscess, fluid accumulation decreased; bacterial examination showed no positive findings. Another year later, the patient's condition relapsed. We thought that the empyema may have been caused by endoclips that had migrated. We performed thoracoplasty and retrieved three endoclips from the intrathoracic empyema cavity. The patient showed good recovery after the operation.

Survivorship Bias after Military Thoracic Injuries

We read with interest the article by Morrison et al. [1] about military ballistic thoracoabdominal injuries from a British Military Hospital in Afghanistan. In their series of 27 patients, many required surgical exploration either at presentation or after further investigation with CT. The study prompted us to review retrospectively our experience during a similar period. The medical records and CT scans of 21 soldiers transferred from Afghanistan military field hospitals to The Royal Centre for Defense Medicine Selly Oak Hospital and Queen Elizabeth Hospital, Birmingham, United Kingdom, between July 2006 and October 2008 for thoracic injuries were examined. The mean age of the soldiers was 29 years (standard deviation (SD), 2.7), and 11 (52%) were intubated upon arrival with a further 4 subsequently requiring intubation. Three intubated soldiers were related to presence of flail chest from trauma. Sixteen soldiers suffered from blast injuries and three from bullet injuries (only one penetrated the intrathoracic cavity). Eleven had pneumothoraces that required intercostal drainage. Seven patients had shrapnel injuries (Fig. 1), and five patients had formal chest wall wound debridement. None required surgical intervention to the lungs. One patient required sternotomy for intramyocardial shrapnel removal in nonemergent setting (Fig. 2). The mean (±SD) Injury Severity Scale Score for the patients was 6 (±5). Conservative management was adopted for the remaining cases. Mean hospital stay was 32 days, and there was no mortality at 9 months follow-up. As expected, there is a clear contrast in the severity of injuries and management strategies between soldiers treated at military field hospital and those stable enough to be transferred back to United Kingdom. Interestingly, thoracotomy was not required for any of our patients, whereas it was performed and therapeutic in select cases at the frontline hospital. Previous series on military injury reported emergency thoracotomy was necessary in 12–15% of cases of thoracic trauma, indicated usually in those with cardiovascular collapse from uncontrolled intrathoracic hemorrhage [2]. It is well accepted that those patients with penetrating injury arriving to medical centers with signs of life or those who had prehospital time of less than or equal to 30 min do best in emergency thoracotomies [2, 3]. Furthermore, the procedure is almost universally unsuccessful in patients of class 1 (no signs of life) or class 2 (agonal; with pulseless electrical activity) in advanced trauma life support/early management of severe trauma (ATLS/EMST) terms [2]. The cohort of patients who arrived at our centre clearly fell outside of these categories, having already had initial assessment and appropriate emergency resuscitation at field hospitals. Our patient group, similar to that described by Rosenblatt et al. [2] consisted of those who initially survived the thoracic injury after primary treatment—surgical or conservative—and were successfully transferred to specialist trauma C. S. H. Ng (&) M. J. Underwood Department of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China e-mail: calvinng@surgery.cuhk.edu.hk

Laparoscopic repair of large hiatal hernia: impact on dyspnoea

This study aims to examine the impact of laparoscopic repair of large hiatal hernia on dyspnoea severity, respiratory function and quality of life. From 2004 to 2008, 30 consecutive patients with large para-oesophageal hernia defined as >50% of stomach in the intra-thoracic cavity and minimum follow-up of 2 years were included in this study. All patients had a formal respiratory function test 1 week prior and 3 months after their laparoscopic hiatal hernia repair. Patients rated symptom severity and completed a quality-of-life questionnaire [Gastrointestinal Quality of Life Index (GIQLI)] pre-operatively, and post-operatively at 3 months, 6 months and yearly thereafter. There was no hospital mortality, and the morbidity rate was 10%. In 26 patients with pre-operative dyspnoea, 22 had complete resolution while the remaining 4 had improvement of dyspnoea severity post-operatively. The mean dyspnoea severity index reduced from 2.4 to 1.3 (P < 0.001). Overall, there was 1%, 3% and 3% post-operative increase in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) values for the whole group, none of which reached statistical significance. For patients with resolution or improvement of dyspnoea after laparoscopic repair, no significant change of respiratory function parameters was demonstrated. GIQLI score improved from a pre-operative value of 85.7 to 107.9 post-operatively (P < 0.001). We failed to show a significant change in post-operative respiratory function despite clearly demonstrated improvement of respiratory symptoms. Alternative explanations for reduction of dyspnoea severity should be sought.

Intrathoracic application of a vacuum-assisted closure device in managing pleural space infection after lung resection: is it an option?

Empyema after lung resection is a challenging condition to manage and is associated with a high mortality. Intrathoracic application of a vacuum-assisted closure (VAC) device is recently introduced as an adjunct in the management of this condition. A best evidence topic was constructed to address whether this approach is effective in successful chest closure and reducing hospital stay. Twenty-three papers were found using the reported search, of which nine papers were identified that provided the best evidence to answer the question. All papers were retrospective and included a total of 69 patients treated with intrathoracic VAC. There was only one cohort study and the rest were either case series or case reports. In a cohort of 19 patients reported by Palmen et al. the average duration of an open window thoracostomy in a group of patients with VAC (n=11) was 39 ± 17 days and in those without VAC (n=8) was 933 ± 1422 days. Median length of VAC treatment was 22 days (range 6-66 days) in a series of 28 patients reported by Saadi et al. Some authors excluded patients with a bronchopleural fistula (BPF) from VAC treatment. However, Groetzner et al. have safely used VAC in patients with BPF after covering the bronchus stump with an intrathoracic muscle flap. The mediastinum and the bronchus can be covered using a polyvinyl-alcohol foam. Polyurethane foam is commonly used to fill the intrathoracic cavity up to the superficial wound. The suggested starting level of negative pressure is as low as -25 mmHg to -75 mmHg depending on the presence or absence of signs of mediastinal traction; this negative pressure can gradually be increased to -125 mmHg over time. The recommended interval between VAC changes is two to five days. Accumulated evidence in this article, although limited, suggests that VAC, as an adjunct to the standard treatment, can potentially alleviate the morbidity and decrease hospital stay in patients with empyema after lung resection. VAC can reduce inpatient length of treatment and can make the condition manageable in an outpatient setting. These results are yet to be proven by larger studies and clinical trials.

Synovial sarcoma in the right atrium and right ventricle

A metastatic synovial sarcoma in the right atrium and ventricle is described. A 36-year-old man was admitted to our hospital with generalized fatigue, dyspnoea, and precordial pain. Transthoracic echocardiography demonstrated a metastatic tumour in both the right atrium and right ventricle and revealed obstruction of the infl ow tract of the right ventricle caused by a metastatic right atrial tumour. Thoracic computed tomography revealed a pleural-based paravertebral mass in the left intrathoracic cavity and multiple pulmonary nodules in both lungs. Cardiac surgery was performed for palliative treatment due to right cardiac failure and a risk of fatal embolization. The patient died 12 months after the cardiac surgery.

Emergent Completion Pneumonectomy for Postoperative Hemorrhage from Rupture of the Infected Pulmonary Artery in Lung Cancer Surgery

Completion pneumonectomy (CP) is one of the most difficult procedures and known to be associated with a high morbidity and mortality. A 74-year-old male underwent a left upper lobectomy for pulmonary adenocarcinoma (T3N0M0); six days later after the surgery, he had a sudden postoperative intrathoracic excessive hemorrhage with shock. Emergent redo thoracotomy was performed to treat the bleeding from the ablated interlobar pulmonary artery by suturing with prolene. However, 3 days later after the second operation, he had the second intrathoracic bleeding. Emergent CP was performed with cardiopulmonary bypass by anterior transpericarsial approach via a median sternotomy. The hemorrhage was caused by a rupture of the proximal fragile and infected pulmonary artery. We performed omentopexy for the infected intrathoracic cavity and for covering of the divided main bronchial stump. We had a rare experience of two times of postoperative life-threatening hemorrhage from rupture of the infected pulmonary artery after left upper lobectomy. Emergent CP as salvage surgery should have an advantage in control of infected proximal pulmonary arterial hemorrhage. We should take care of tearing off of adventitia of pulmonary artery in lobectomy because of a possibility of postoperative hemorrhage under a fragility of the injured pulmonary artery with infection.

Intrathoracic Gastric Activity on Cholescintigraphy Results in a Large Hiatus Hernia With Duodenogastric Reflux

When a radiopharmaceutial is seen in the intrathoracic cavity on Tc-99m iminodiacetic acid (IDA) cholescintigraphy, basically 2 abnormalities are seen: first the stomach, such as a hiatus hernia, which is abnormally located in the thoracic cavity, and duodenogastric reflux (bile) which is simultaneously seen. However, intrathoracic gastric activity seen on Tc-99m IDA hepatobiliary scintigraphy is rarely documented in a patient with hiatus hernia. This report is of an 83-year-old man with a large hiatus hernia with duodenogastric reflux who underwent hepatobiliary scintigraphy; the scans show an area of increased activity on the top of the liver due to duodenogastric reflux in a large hiatus hernia. This was confirmed by surgery: the patient successfully underwent laparoscopic paraesophageal hernia repair with Nessen fundoplication and laparoscopic cholecystectomy.

Pathological fracture due to vertebral osteonecrosis associated with pancreatitis

A 50-year-old man with a history of alcohol-induced pancreatitis was admitted to a hospital with swelling and pain of the right ankle, and fever, and was suspected to have osteomyelitis. Radiographs of the fingers, ankles, and feet, in which pain and swelling were present, revealed multiple pathological fractures. The histological examination of the tissue sample in the right radius showed sequestrated fat necrosis. Bacterial culture test remained negative. Based on the findings mentioned above, a diagnosis of intraosseous fat necrosis associated with pancreatitis was made. Treatments proven to be effective in the literature for pancreatitis were started. Symptoms of the bones and joints gradually improved. However, pancreatitis relapsed, triggered by drinking, 4 months after discharge. He had complaints of back pain without any history of trauma. Radiographs showed fractures of the entire vertebral body from the 12th thoracic to 5th lumbar vertebrae. What was interesting about the present case was that, after the pathological fractures of the extremities were completely resolved, osteonecrosis relapsed as pancreatitis deteriorated, resulting in pancreatic cyst rupture into the intrathoracic cavity and vertebrae, differing from the previous lesions that were affected. There are very few cases of pathological fracture induced by pancreatitis that affect the vertebrae.

Supradiaphragmatic Heterotopic Liver Presenting as a Pleural Mass: A Case Report

Abnormally located liver tissue has been described in the vicinity of the liver proper, near anatomical structures such as the gallbladder, the umbilical fossa, the adrenal gland, the pancreas, and the spleen. Supradiaphragmatic ectopic liver is a rare finding, but has been reported to have been found in the intrathoracic cavity and in the pericardium. In the majority of supradiaphragmatic ectopic liver cases, there was an accompanying transdiaphragmatic pedicle of the main liver body into the abdominal cavity. In a minority of supradiaphramatic ectopic liver cases, the liver was completely separated from the abdominal cavity without a connection between the thorax and the abdomen, with accompanying diaphragmatic anomalies. We describe one case of intrathoracic ectopic liver in a patient with a previous history of lower chest wall trauma, and a brief review of the English-language medical literature on this topic.

HP23P LAPAROSCOPIC LARGE HIATAL HERNIA REPAIR – IMPACT ON RESPIRATORY FUNCTION AND QUALITY OF LIFE

Purpose: This study is to examine the impact of laparoscopic repair of large hiatal hernias on patient's respiratory function and quality of life.Methodology: From 2004 to 2008, 30 consecutive patients with large paraesophageal hernias defined as &gt;50% of stomach in the intrathoracic cavity with a minimum follow‐up of 2 years were included in this study. All the patients had formal respiratory function test 1 week prior and 3 months after their laparoscopic hiatal hernia repair. The patients had to rate their symptom severity and complete a quality of life questionnaire (GIQLI) preoperatively and then at 3‐month, 6‐month and thereafter yearly intervals postoperatively.Results: There were no hospital mortality and the morbidity rate was 10%. In 26 patients with preoperative dyspnoea, 22 had complete resolution while the remaining 4 had experienced improvement in dyspnoea severity postoperatively. The mean dyspnoea severity index reduced from 2.4 to 1.3(p &lt; 0.001). Overall, there was 1%, 3% and 3% postoperative increase in FEV1, FVC and DLCO values for the whole group, none of which reached statistical significance. For the patients with resolution or improvement of their dyspnoea after the laparoscopic repair, no significant changes in their respiratory function parameters were demonstrated. The GIQLI score improved from a preoperative value of 85.7 to 107.9 postoperatively (p &lt; 0.001).Conclusion: We failed to show a significant change in patient's respiratory function despite a clearly demonstrated improvement of their respiratory symptoms. Alternative reasons for the reduction of dyspnoea severity should be sought. Laparoscopic hiatal hernia repair is also a safe procedure that can lead to better patient quality of life.

Effective Approach for the Treatment of Bronchopleural Fistula: Application of Endovascular Metallic Ring-Shaped Coil in Combination With Fibrin Glue

The development of bronchopleural fistula is an important complication after pulmonary resections. Generally, conventional treatment methods are used in patients having bronchopleural fistulas. Recently, there has been an increase in the use of minimally invasive methods yielding better results. In our study, we applied a combination of endovascular metallic ring coil and fibrin glue. We hereby think that such an approach for a combination might be a contribution to improving the already existing minimally invasive treatment methods.

Risk Factors for an Intraoperative Arrhythmia during Esophagectomy

PurposeArrhythmias after an esophagectomy (most commonly atrial fibrillation) are a significant contributing factor to patient morbidity. However, the significance of an intraoperative arrhythmia is not completely understood. The aim of this retrospective study was to determine the occurrence and risk factors for developing intraoperative arrhythmias in patients undergoing an esophagectomy.Materials and MethodsWe reviewed the records of 427 patients who underwent a transthoracic esophagectomy between 2001 and 2005. Variables such as age, sex, hypertension, diabetes, cardiac disease, preoperative pulmonary function test (PFT) results, cancer level, combined radiochemotherapy, intrathoracic cavity adhesions and anastomosis site, hemoglobin, central venous pressure (CVP), fluid balance, serum potassium level, dose of vasopressors, temperature, and combined general and epidural anesthesia were analyzed as risk factors for the occurrence of an arrhythmia. We defined this arrhythmia as one not originating from the sinus node.ResultsThe incidence of intraoperative arrhythmia in this subset of patients was 17.1%, with a 37.2% reoccurrence rate during the first three postoperative days. Univariate and multivariate analysis revealed the presence of heart disease, poor PFTs, cervical anastomosis, elevated CVP, and higher ephedrine doses to be independent predictors of the development of an intraoperative arrhythmia.ConclusionThe incidence of intraoperative arrhythmia during esophagectomy was 17.1% with a 37.2% of reoccurrence rate.

Complete Ectopia Cordis

Complete ectopia cordis is a very rare condition. With few exceptions, it is uniformly considered fatal. Death usually occurs within the first days of life as a result of infection, cardiac failure, or hypoxemia. We report the case of a male infant with Cantrell’s syndrome. There was complete thoracic exteriorization of the heart, with cephalic orientation of the cardiac apex (Figure 1). The cardiac surface was covered by …

Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6

Vectors based on recombinant adeno-associated viruses (rAAV) have emerged as tools of choice for gene transfer to skeletal muscle. rAAV vectors demonstrate efficient, safe, and stable transduction. Multiple serotypes of AAV exist, but vectors based on serotype 2 (rAAV2) are the most thoroughly characterized and frequently employed. Here, we characterize transduction of the skeletal musculature using rAAV vectors pseudotyped with serotype 6 capsid proteins (rAAV6). We demonstrate that rAAV6 vectors can efficiently transduce the skeletal musculature of mice at levels >500-fold higher than is achievable with rAAV2 vectors and can readily saturate individual muscles following direct injection. Further, rAAV6 vectors are capable of transducing the diaphragm and intercostal muscles of mice after a simple injection into the intrathoracic cavity and are capable of widespread transduction throughout the musculature of mice injected in the intraperitoneal space as newborn pups. These results demonstrate that rAAV6 vectors hold great potential for use in gene delivery protocols targeting the skeletal musculature.