David N. Ostrow

Glandular neoplasia of the lung. A proposed analogy to colonic tumors

In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1‐ to 1‐cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1‐ to 2‐mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively.

Lingular and Right Middle Lobe Biopsy in the Assessment of Diffuse Lung Disease

It has been said that the lingula and right middle lobe should be avoided for open-lung biopsy because of nonspecific fibrosis and vascular changes. To determine if the diagnostic yields of lingular or right middle lobe biopsy specimens were unsatisfactory, we reviewed the results of open-lung biopsy in 73 adult patients; 26 were immunocompromised and 47, nonimmunocompromised. We found no evidence to suggest that these two sites were inherently inferior. In 20 of the nonimmunocompromised patients, computed tomography was performed prior to biopsy, and demonstrated no particular tendency for greater involvement of the lingula or right middle lobe. We conclude that lingular and right middle lobe biopsy is useful in the diagnosis of parenchymal lung disease and that these sites should not necessarily be avoided. Computed tomographic scanning prior to biopsy is helpful in guiding the surgeon to the appropriate sites from which to obtain biopsy specimens.

A young woman with episodic angioedema, papilledema, and eosinophilia

A 21-year-old Chinese woman presented to the Emergency Department with a 6-week history of progressive headache, blurred vision, exertional dyspnea and limb claudication, mild epistaxis, and heavy menses. This was preceded by a 15-month history of episodic erythematous maculopapular rash and limb swelling. She had no fever, weight loss, or night sweats. Her past history was significant for glucose-6-phosphate dehydrogenase (G6PD) deficiency and she was on nortriptyline for headaches. She was not sexually active, had not traveled, and used no recreational substances. This syndrome of headache, visual disturbance, claudication, and mucosal bleeding suggests disruption of the microvasculature and platelet dysfunction such as seen in hyperviscosity syndrome. Increased serum viscosity may be due to hypergammaglobulinemia (monoclonal or polyclonal) or cryoglobulinemia and may lead to neurologic defects, mucosal bleeding, and thrombosis. Increased cellular viscosity is seen in conditions such as acute leukemia (leukostasis), myeloproliferative neoplasms, or sickle cell crisis and typically affects small vessels of the lungs and brain. The limb claudication, neurologic symptoms, and skin rash may also indicate a systemic vasculitis. Her transient limb swelling suggests angioedema. G6PD deficiency is typically an X-linked recessive disorder and therefore unusual in females but a hemolytic workup is appropriate if she is anemic. Physical examination revealed a pale thin young woman. Her temperature was 36.88C, blood pressure 115/65 mmHg (no pulsus paradoxus), heart rate 130 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 98% on ambient air. Head and neck examination revealed multiple bilateral 1–2 cm soft, mobile cervical lymph nodes. Her jugular venous pressure (JVP) was at the angle of her jaw while at 908 and she had a loud pulmonic component of the second heart sound (P2), but no right ventricular heave. Her liver edge was palpable 6 cm below the costal margin, the span was 18 cm by percussion, and there was no splenomegaly. Fundoscopy revealed papilledema with tortuous ‘‘sausage’’ vessels, indistinct optic disk margins and absence of arterial pulsations. The rest of her neurologic exam was unremarkable. She had no rash, swelling, or joint effusions. Bloodwork done 1 week before revealed white-cells 13.9 3 10 per liter, eosinophils 3 10 9.1 3 10 per liter (normal 0.7), hemoglobin 75 g per liter, platelet count 205 3 10 per liter, total protein 137 g per liter (normal 62–82), albumin 31 g per liter, and gamma globulin 91 g per liter (normal 5.1–15) with a focally increased gamma-globulin peak. Immunofixation revealed predominantly IgG with corresponding lambda and kappa light chain bands of equal intensity. Creatinine was 82 lmol per liter, and urine was negative for blood and protein. An abdominal ultrasound 1 week before showed mild hepatomegaly of 17.9 cm with porta-hepatis lymphadenopathy measuring up to 2.7 cm, but no splenomegaly and no other intra-abdominal lymphadenopathy. The markedly elevated immunoglobulin G (IgG) levels and papilledema confirm the hypothesis of hyperviscosity syndrome. Equal kappa and lambda light chain intensity indicates a polyclonal gammopathy, although with such high levels, a monoclonal element cannot be excluded. Structural causes of raised intracranial pressure must be ruled out. Polyclonal hypergammaglobulinemia and eosinophilia may be associated with connective-tissue disease such as the Churg-Strauss syndrome, lymphoproliferative disorders such as angioimmunoblastic T-cell lymphoma (AILT), and idiopathic eosinophilia. Malignancy and parasitic infection with multiorgan involvement (such as strongyloides stercoralis) should be ruled out. Medication reactions, atopic disease, and adrenal insufficiency may be associated with reactive eosinophilia and/or hypergammaglobulinemia but are unlikely in this case. She has evidence of pulmonary hypertension with right ventricular failure (elevated JVP, loud P2, and hepatomegaly). This may be related to hyperviscosity. Hyperviscosity increases the risk of vascular thrombosis, so an electrocardiogram and cardiac enzymes should be done, as well as a computed tomography pulmonary angiogram to rule out

Noninvasive Investigations for the Early Detection of Chronic Airways Dysfunction Following Lung Transplantation

BACKGROUND The diagnosis of chronic rejection after lung transplantation is limited by the lack of a reliable test to detect airways disease early. OBJECTIVES To determine whether maximum midexpiratory flow (MMEF), or changes on high resolution computed tomography (HRCT) or ventilation/perfusion lung (V/Q) scans are sensitive and specific for early detection of bronchiolitis obliterans syndrome (BOS; forced expiratory volume in 1 s [FEV1] less than 80% post-transplant baseline) by evaluating long term survivors of lung transplantation at two sequential time points. METHODS Twenty-two stable lung transplant recipients underwent spirometry, HRCT scanning and V/Q scanning 1.6 +/- 0.9 years and 3.1 +/- 1.1 years post-transplant (time points 1 and 2, respectively; mean +/- SD). RESULTS Although HRCT was sensitive for the detection of BOS, it lacked specificity, and hence, there were no significant relationships between the presence of BOS and any of the HRCT parameters evaluated at time 1 or time 2. Of the V/Q parameters studied, the presence of heterogeneous perfusion (P=0.04, sensitivity 100%, specificity 33%) and segmental perfusion defects (P=0.04, sensitivity 60%, specificity 83%) were significantly related to BOS, but only at time 2. MMEF less than or equal to 75% post-transplant baseline was significantly related to the presence BOS at time 1 only (P=0.05, sensitivity 100%, specificity 47%). MMEF less than or equal to 75% post-transplant baseline at time 1 was sensitive for the development of BOS at time 2, but was limited by low specificity. CONCLUSIONS In this group of lung transplant recipients, HRCT and V/Q scanning, as well as analysis of MMEF, did not add information that was clinically more useful than FEV1 for the early identification of chronic rejection.

Transition from Intravenous Epoprostenol to Oral or Subcutaneous Therapy in Pulmonary Arterial Hypertension: A Retrospective Case Series and Systematic Literature Review

BACKGROUND: Intravenous epoprostenol, a prostaglandin analogue, has been a mainstay of therapy for patients with advanced pulmonary arterial hypertension (PAH) since the early 1990s. This medication has multiple side effects, and sudden discontinuation is potentially associated with severe sequelae. Several recent case series have described the transition from intravenous to newer oral or subcutaneous therapies. A case series detailing the authors’ experience with such transitions, and a systematic lierature review is presented.

Assessing Response to Therapy in Idiopathic Pulmonary Arterial Hypertension: A Consensus Survey of Canadian Pulmonary Hypertension Physicians

BACKGROUND Many treatment options are now available for patients with idiopathic pulmonary arterial hypertension (IPAH). Data regarding the optimal combination of therapies are lacking, as is consensus on how to assess response to therapy and when to change therapeutic regimens. OBJECTIVES To gather the opinions of Canadian pulmonary hypertension (PH) experts regarding standard practice in the care of IPAH patients after therapy is initiated. METHODS Canadian PH physicians were surveyed using short questionnaires to assess their opinions and practices in the care of IPAH patients. A Delphi forecasting approach was used to gain consensus among Canadian physicians on the most important clinical parameters to consider when assessing patients after the initiation of therapy. RESULTS Twenty-six of 37 Canadian PH experts who were invited to participate completed the study. All endorsed the use of combination therapy for IPAH patients despite the lack of universal provincial coverage for this approach. By consensus, WHO functional class, 6 min walk distance and hospitalization for right heart failure were the most important clinical parameters. The most highly rated physical examination parameters were jugular venous pressure, peripheral edema, the presence of ascites and body weight. CONCLUSIONS The overall approach to care of IPAH patients is similar across PH centres in Canada. A limited number of clinical and physical examination parameters were considered to be most important to reassess patients after therapy is initiated. These parameters, along with definition of threshold values, will facilitate the development of standard practice guidelines for IPAH patients in Canada.

Lung Volume Reduction Surgery following Single-Lung Transplantation

Although single-lung transplantation is an established therapy for respiratory failure secondary to emphysema, hyperinflation of the native lung with concomitant compression of the transplanted lung is emerging as a cause of morbidity. In non-transplant emphysematous patients with hyperinflated lungs, pneumectomy was found to improve pulmonary function and quality of life. We report our experience on 5 single-lung transplant recipients with emphysema who underwent lung volume reduction surgery (pneumectomy, bullectomy, or anatomic resection) following transplantation. There were no perioperative deaths. Three patients underwent lung volume reduction because of a progressive symptomatic decline in pulmonary function that was thought to be secondary to hyperinflation of the native lung. Two of these patients had a sustained improvement in lung function and functional status over several years. Two other patients underwent lung volume reduction for removal of suspicious pulmonary nodules in the native lung. Both patients had a subsequent improvement in forced expiratory volume in one second. In our experience, lung volume reduction surgery after single-lung transplantation in emphysematous patients was a safe means of providing long-term improvement in pulmonary function.