Primary Lung Cribriform Adenocarcinoma With Squamoid Morules Harboring Somatic CTNNB1 Mutation in a Never-Smoked Healthy Adolescent.

Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified CTNNB1 mutation in the tumor and excluded other common mutations in lung adenocarcinoma. Our case suggests molecular alterations to the same signaling pathway can lead to similar histomorphology regardless of the tissue of origin.

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

Evaluation of clonal origin of malignant mesothelioma.

BACKGROUND: The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy. METHODS AND RESULTS: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM. CONCLUSIONS: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs.

BACKGROUND: BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline BAP1 mutations and increased risk of malignant mesothelioma. METHODS: Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ2 test or two-tailed Fisher's exact test). RESULTS: Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call "melanocytic BAP1-mutated atypical intradermal tumors" (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001). CONCLUSIONS: Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline BAP1 mutations and thus are at high risk of developing associated cancers.

Components of geriatric assessments predict thoracic surgery outcomes.

BACKGROUND: No tool currently exists to rapidly allow surgeons to objectively quantify surgical risk in geriatric patients. The goal of our prospective study was to determine if individual questions extracted from validated screens for common geriatric syndromes would have predictive value for surgical risk in geriatric patients with thoracic neoplasms. METHODS: Patients ≥ 70 y old were recruited to participate in a prospective, IRB-approved study involving the preoperative administration of validated screening tests. Patients were given the geriatric depression scale (GDS), nutrition screening initiative nutritional health checklist (NSI NHC), mini mental status exam (MMSE), brief fatigue inventory (BFI), and assessed for activities of daily living (ADLs) and instrumental activities of daily living (IADLs). All patients enrolled in this study were scheduled for thoracic surgery. RESULTS: Patients who responded to having a dependency in the IADL "shopping" were more likely to have major complications and to be discharged to a non-home location than those without a dependency (P = 0.011, 0.003). Patients who answered "yes" to questions 1, 9, and 10 of the NSI NHC had a longer mean length of stay compared with patients who answered "no" (P = 0.039, 0.010, 0.031). Answering "yes" to GDS question 2 correlated with the incidence of major complications (r = 0.270 P = 0.037). Answering "yes" to GDS question 12 increased the likelihood of being discharged to a non-home location postoperatively (odds ratio = 11.64, 95% CI, 0.68-202.86, P = 0.047). CONCLUSIONS: Our data indicate that an abbreviated, rapid presurgical assessment can be developed for estimating operative risk, length of stay, and discharge destination in geriatric patients with thoracic malignancies using individual questions from previously validated screening tools.

Implementation of an Acuity Adaptable Patient Care Unit is associated with improved outcomes after major pulmonary resections.

BACKGROUND: Many centers have adapted an Acuity Adaptable Cardiothoracic Unit (AACU) to fast track cardiac surgery patients, yet few data exist on the impact of such a unit on general thoracic surgery outcomes. We examined the effects of implementing an Acuity Adaptable Cardiothoracic Unit on patients undergoing major pulmonary resections. METHODS: We reviewed data from an IRB-approved, prospective thoracic surgery database for patients during the 3-y periods pre- and post-adoption of an Acuity Adaptable Cardiothoracic Unit. As surrogate endpoints to quality and cost, we examined length of stay, place of discharge, readmission rate, and 30-d mortality during these two time periods. RESULTS: A total of 488 patients underwent major pulmonary resections (416 lobectomies, 72 pneumonectomies) in this 6-y time period. Patients cared for in the AACU model had a shorter length of stay (LOS) compared with patients in a traditional ICU/general care model. The mean and median LOS for patients in the AACU model was 4.2 ± 0.3 d and 3 d, and for the traditional ICU/general care model these were 7.8 ± 1.2 d and 5 d, respectively (P < 0.001). Relative risk of readmission was 0.86 (95% CI = 0.45, 1.66, P = 0.392) and 30-d mortality was 0.49 (95% CI = 0.14, 1.68, P = 0.205) for patients in the AACU model compared with patients in the traditional ICU/general care unit. CONCLUSIONS: Implementation of an Acuity Adaptable Cardiothoracic Unit is associated with reduced length of hospital stay in patients undergoing major lung resections, without increased risk of readmission or 30-d mortality. Future studies will evaluate post-operative events unique to an AACU model.

The Answer to the Silent "Super Spreader": An Innovative Way to Manage Chest Drains on Coronavirus Patients With Active Air Leaks.

The risk of aerosol transmission has been a key factor for the rapid dissemination of the coronavirus pandemic. Transportation of coronavirus disease 2019 (COVID-19)-infected patients with active air leaks could expose unprotected health care personnel and other patients to aerosolized viral particles. We devised a way to avoid aerosolization while the chest tube drain is on water seal. It involves placing an Ultipor100 viral filter on the suction port of the drain system as well as sealing off the safety valve. This mechanism allows positive pressure from an air leak to escape while on water seal while trapping viral particles.

Humeral Head Fracture Dislocation with Displacement into the Mediastinum: A Case Report.

CASE: A 70-year-old woman pedestrian struck by a motor vehicle presented with multiple orthopaedic injuries including a humeral head fracture dislocation with a large segment of humeral head located in the mediastinum. Thoracic surgery personnel performed a minimally-invasive video-assisted thoracoscopic extraction of the humeral head, and the patient underwent subsequent reverse total shoulder arthroplasty. CONCLUSION: Intramediastinal displacement of the humeral head is a rare, yet serious traumatic injury that necessitates early recognition and comanagement with cardiothoracic or thoracic surgery. Early thoracic intervention to extract the humeral head and replacement arthroplasty is an effective treatment modality.

An Innovative Way to Achieve Safe Lung Deflation During One-Lung Ventilation in a Potential Coronavirus Disease 2019 Patient: A Case Report.

A novel coronavirus pandemic may be particularly hazardous to health care workers. Airway management is an aerosol-producing high-risk procedure. To minimize the production of airborne droplets, including pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the endotracheal tube during procedures requiring lung deflation, we devised a technique to mitigate the risk of infection transmission to health care personnel.

Management of air leaks post-surgical lung resection.

Airleaks are one of the most common complications associated with elective lung resection. There have been many techniques and modern advancements in thoracic surgery, however airleaks persist. This review article will discuss several interventions ranging from conservative noninvasive to surgical management of the persistent airleak. These techniques include stopping of suction on the plueravac, fibrin patches, pleurodesis, use of endobronchial valves (EBVs), return to OR for operative intervention, and lastly to send patients home with mini pleuravacs.

Minimally invasive esophagectomy for malignant and premalignant diseases of the esophagus.

Minimally invasive approaches increasingly are used to treat esophageal cancer and Barrett's esophagitis with high-grade dysplasia. The goals of a minimally invasive esophageal resection are to provide sound oncologic therapy while minimizing morbidity. This article describes the technique the authors use for laparoscopic-thoracoscopic esophagectomy. Comparison data are presented for alternative endoscopic therapy primarily used in candidates not suitable for surgery.

Acute esophageal necrosis: "black esophagus".

Acute esophageal necrosis (AEN) is an uncommon event. We report a case of an 84-year-old female with a giant paraesophageal hernia who presented with coffee ground emesis and on esophagogastroduodenoscopy (EGD) demonstrated findings consistent with acute esophageal necrosis and a giant paraesophageal hernia with normal-appearing gastric mucosa. She was managed conservatively with bowel rest, parenteral nutrition, and continuous intravenous proton pump inhibitor (PPI). After significant improvement in the gross appearance of her esophageal mucosa, surgery was performed to reduce her giant paraesophageal hernia. The patient's postoperative course was uneventful, and she was discharged home on postoperative day 6, tolerating a normal diet. The percutaneous endoscopic gastrostomy (PEG) tube was removed in clinic 2 months postoperatively.

The need for intraoperative parathyroid hormone monitoring during radioguided parathyroidectomy by video-assisted thoracoscopy (VATS).

PURPOSE: We report on a patient with primary hyperparathyroidism (1HPT) who had a preoperative Tc-99m sestamibi scan localizing a single parathyroid adenoma in the mediastinum. METHODS: On removal of this hyperfunctioning adenoma by radioguided video-assisted thoracoscopic surgery (VATS), intraoperative PTH levels failed to decline in the appropriate manner consistent with curative resection. This prompted the surgical team to investigate further for a second adenoma, which revealed a 2 x 1-cm mass near the inferior border of the thyroid gland on the right lateral aspect of the trachea. RESULTS: In the absence of intraoperative PTH monitoring, the operation would have been terminated after the removal of the mediastinal adenoma, leading to an incomplete surgical resection and persistent 1HPT. CONCLUSION: In our patient, curative resection was obtained and a second operation was avoided because of the use of intraoperative PTH monitoring. This case also emphasizes that although VATS was planned, in treating patients with 1HPT, one must also be prepared to perform a neck exploration.

A Twelve-Year Consecutive Case Experience in Thoracic Reconstruction.

BACKGROUND: We describe the second largest contemporary series of flaps used in thoracic reconstruction. METHODS: A retrospective review of patients undergoing thoracomyoplasty from 2001 to 2013 was conducted. Ninety-one consecutive patients were identified. RESULTS: Thoracomyoplasty was performed for 67 patients with intrathoracic indications and 24 patients with chest wall defects. Malignancy and infection were the most common indications for reconstruction (P < 0.01). The latissimus dorsi (LD), pectoralis major, and serratus anterior muscle flaps remained the workhorses of reconstruction (LD and pectoralis major: 64% flaps in chest wall reconstruction; LD and serratus anterior: 85% of flaps in intrathoracic indication). Only 12% of patients required mesh. Only 6% of patients with <2 ribs resected required mesh when compared with 24% with 3-4 ribs, and 100% with 5 or more ribs resected (P < 0.01). Increased rib resections required in chest wall reconstruction resulted in a longer hospital stay (P < 0.01). Total comorbidities and complications were related to length of stay only in intrathoracic indication (P < 0.01). Average intubation time was significantly higher in patients undergoing intrathoracic indication (5.51 days) than chest wall reconstruction (0.04 days), P < 0.05. Average hospital stay was significantly higher in patients undergoing intrathoracic indication (23 days) than chest wall reconstruction (12 days), P < 0.05. One-year survival was most poor for intrathoracic indication (59%) versus chest wall reconstruction (83%), P = 0.0048. CONCLUSION: Thoracic reconstruction remains a safe and successful intervention that reliably treats complex and challenging problems, allowing more complex thoracic surgery problems to be salvaged.

Transgastric laparoscopic resection of a giant esophageal lipoma.

We present an unusual case of a giant, pedunculated esophageal lipoma originating in the mid-esophagus ball-valving through the gastroesophageal junction resulting in intermittent obstruction and hemorrhage. Endoscopic ultrasonography revealed a 1 cm in diameter vessel in the stalk of the polyp, and endoscopic resection was not performed. Transgastric laparoscopic resection with endoscopic guidance was successfully performed using 2 balloon-tipped laparoscopic trocars inserted laparoscopically into the gastric lumen through separate gastrotomies. Intraoperative esophagoscopy confirmed proper port placement and the exact location of the mass. Under direct visualization, a Snowden-Pencer grasper was used to pull the polyp down into the stomach and an Endo-GIA blue articulating stapler was used to transect its stalk. The polyp was retrieved via an endopouch placed through the intragastric laparoscopic port. We conclude that transgastric laparoscopy should be considered for the resection of a variety of pedunculated esophageal lesions when the use of standard endoscopic techniques is not possible.

Radioguided parathyroidectomy via VATS combined with intraoperative parathyroid hormone testing: the surgical approach of choice for patients with mediastinal parathyroid adenomas?

Despite the excellent results with bilateral exploration, minimally invasive parathyroidectomy has become the procedure of choice for patients with hyperparathyroidism in which a single parathyroid lesion can be localized preoperatively. In this article, we discuss a patient who presented with primary hyperparathyroidism for the first time and had a Tc-99m sestamibi scan to localize a single parathyroid lesion in the left, anterior mid-mediastinum. We subsequently performed a radioguided parathyroidectomy via video-assisted thoracoscopic surgery (VATS) to resect this parathyroid adenoma and used intraoperative parathyroid hormone (PTH) testing to confirm cure and avoid neck exploration. We concluded that radioguided parathyroidectomy via VATS combined with intraoperative PTH testing is an effective approach for patients with primary hyperparathyroidism and mediastinal parathyroid lesions, and perhaps should be the technique of choice.

Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model.

OBJECTIVE: Innovative treatments are needed for metastatic disease involving the pleura. NV1020 is a novel, multimutated, replication-restricted herpes simplex virus under investigation for its ability to selectively kill tumors by means of direct cell lysis. This study examines NV1020 in a rat model of pleura-based lung cancer. METHODS: Cytotoxicity and viral proliferation were evaluated in vitro by exposure of the human non-small cell lung cancer cell line A549 to virus. NV1020 was also tested in an in vivo pleura-based cancer model established by injecting 1 x 10(7) A549 cells into the thoracic cavity of nude rats. Intrapleural treatments (1 x 10(7) viral particles) were given 3 hours or 3 days after tumor injection to model treatment of microscopic or macroscopic disease (n = 8-9/group). Tumor burden was assessed at 5 weeks. NV1020 infection and dissemination within the thoracic cavity was determined by means of immunohistochemistry. RESULTS: In vitro, at multiplicities of infection (viral particles per tumor cell) of 0.01, 0.1, and 1.0, cell killing of A549 by NV1020 was 66%, 90%, and 97%, respectively, at 7 days after infection. Viral burst occurred by day 2. Intrapleural treatment was effective for both the microscopic (P <.001) and macroscopic (P <.05) in vivo tumor models. Virus was detectable by means of immunohistochemistry in tumors but not in adjacent normal intrathoracic tissues. CONCLUSIONS: NV1020 is not only highly cytotoxic to the human lung cancer line A549 in vitro but can be delivered in a clinically relevant fashion to safely and effectively treat pleura-based tumor in vivo in a rat model.

Chylotamponade: an unusual presentation of Gorham's syndrome.

Gorham's Syndrome, also known as massive osteolysis or "vanishing bone disease" results from lymphangiomatosis with adjacent bone resorption. Chylothorax is a common complication in cases of mediastinal involvement. We report a case of Gorham's Syndrome presenting as chylotamponade successfully treated with pericardial drainage, early parenteral nutritional support, bilateral pleurodesis for chylous effusions, and adjuvant external beam radiation.

Endoluminal palliation for dysphagia secondary to esophageal carcinoma.

There are now a variety of treatment options available to palliate dysphagia in patients with advanced esophageal carcinoma. The decision as to which therapy to recommend for a patient should be based on a though understanding of the therapies and must be individualized for each patient and on the experience of the endoscopist or surgeon. In addition, consideration should be given as to resource availability at a particular institution. External beam radiation currently has little role as primary treatment for dysphagia. Brachytherapy is labor intensive; requires 2 to 3 weekly treatments, highly specialized radiation equipment, and an experienced radiation oncologist; and is therefore limited to tertiary care centers. Endoluminal YAG-laser tumor ablation is feasible at many institutions and provides immediate dysphagia relief but has limited durability (weeks) if not followed by adjuvant therapy, and requires an endoscopist with significant laser experience. PDT is relatively easy to perform and has a lower perforation rate and longer durability than YAG laser therapy but it is relatively costly and less patient friendly due to the morbidity of its attendant 6 weeks of photosensitivity. Advances in stent technology have rendered this a safe, readily available treatment for the palliation of dysphagia. Palliation of dysphagia is an important but difficult goal that may require creative use of a variety of endoscopic interventions, either in combination or serially. Ideally, physicians who palliate dysphagia secondary to esophageal cancer should be facile in both endoscopic ablative and stenting techniques and have a close working relationship with both radiation and medical oncologists.

PET scan-CT correlation: what the chest radiologist needs to know.

The purpose of this article is to familiarize the chest radiologist with the basics of PET scanning in the chest and to correlate PET findings with thoracic CT findings. After completing this article, the reader should know the following: (a) how PET scanning is performed; (b) the indications for PET scanning in the chest; (c) the significance of SUV and a positive test; (c) the causes of false-positive and false-negative PET scans; and (d) the importance of correlating PET findings with Chest CT findings. The authors conclude that PET and chest CT studies should be read in conjunction to optimize diagnostic accuracy. Interpreting either study alone is fraught with errors, while combined interpretations yield information on both functional activity and anatomic localization. PET-CT hybrid devices that fuse PET and CT data simplify this task and fusion imaging is rapidly becoming the test of choice for evaluating thoracic malignancies.