Ken R. Reid

Who should follow up lung cancer patients after operation

BACKGROUND It is unclear whether follow-up by a thoracic surgeon after lung cancer resection alters survival. METHODS The charts of 245 early stage (< or = IIB) non-small cell lung cancer patients, diagnosed between 1988 and 1995, were reviewed. Follow-up data were complete to January 1, 1997, in 96.3% (236 of 245) of cases. RESULTS Ninety of the 111 recurrences were detected before discharge from the thoracic clinic. Despite clinic follow-up, 66.7% (60 of 90) were identified by the family physician, and only 28.9% (26 of 90) by the surgeon. The remaining 4.4% (4 of 90) were detected by other physicians. Ninety-six percent (25 of 26) surgeon-detected recurrences had suspicious clinical or chest radiographic findings, compared with 92% for family physician-detected recurrences (55 of 60; not significant). The cost per recurrence detected by surgeons was Can

Prolonged preservation of canine lung allografts: The role of prostaglandins☆

4,367. A 75% cost savings could ensure if patients were followed up by their family physician. There was no 5-year survival benefit for patients whose recurrence was detected by the surgeon. CONCLUSIONS Long-term follow-up after limited-stage non-small cell lung cancer resection could possibly be performed by a family physician alone without compromising overall survival, and with significant cost savings.

Gap junctional communication in cultured human lung carcinoma cells.

The role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 °C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 °C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 ± 64, 296 ± 75, 79 ± 12, and 71 ± 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p < 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.The role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 degrees C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 degrees C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 +/- 64, 296 +/- 75, 79 +/- 12, and 71 +/- 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p less than 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.

Analysis of CYP2A Contributions to Metabolism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone in Human Peripheral Lung Microsomes

Animal tumor models have demonstrated a close correlation between gap junctional, intercellular communication (GJIC) and tumor metastasis. To examine GJIC levels in human lung carcinoma cells, a novel technique was developed: cells were grown on a glass slide, half of which was coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse which opens transient pores on the plasma membrane was applied in the presence of the fluorescent dye, Lucifer yellow, causing the dyes penetration into the cells growing on the conductive part of the slide. The migration of the dye through gap junctions to the non-electroporated cells growing on the non-conductive area was then observed microscopically under fluorescence illumination. The results show that this is a rapid, precise and highly reproducible assay for GJIC assessment in lines established from lung carcinomas or freshly explanted lung tumor cells. Out of 17 established lines only two had extensive junctional communication, while out of 16 fresh tumor specimens none displayed GJIC. On the other hand, fibroblasts isolated from the same tumors had extensive junctional permeability. The examination of GJIC in a large number of samples could establish a correlation between GJIC and metastasis which might have prognostic value.

The safety of low-dose prednisone before and immediately after heart-lung transplantation

The objectives of this study were to determine the contributions of CYP2A13 and CYP2A6 to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism in human peripheral lung microsomes and to determine the influence of the genetic polymorphism, CYP2A13 Arg257Cys, on NNK metabolism. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the keto-reduced metabolite of NNK, was the major metabolite produced, ranging from 0.28 to 0.9%/mg protein/min. Based on total bioactivation of NNK and NNAL by α-carbon hydroxylation, subjects could be classified as either high (17 subjects) or low (12 subjects) bioactivators [(5.26 ± 1.23) × 10-2 and (6.49 ± 5.90) × 10-3% total α-hydroxylation/mg protein/min, P < 0.05]. Similarly, for detoxification, subjects could be grouped into high (9 subjects) and low (20 subjects) categories [(2.03 ± 1.65) × 10-3 and (2.50 ± 3.04) × 10-4% total N-oxidation/mg protein/min, P < 0.05]. When examining data from all individuals, no significant correlations were found between levels of CYP2A mRNA, CYP2A enzyme activity, or CYP2A immunoinhibition and the degree of total NNK bioactivation or detoxification (P > 0.05). However, subgroups of individuals were identified for whom CYP2A13 mRNA correlated with total NNK and NNAL α-hydroxylation and NNAL-N-oxide formation (P < 0.05). The degree of NNAL formation and CYP2A13 mRNA was also correlated (P < 0.05). Subjects (n = 84) were genotyped for the CYP2A13 Arg257Cys polymorphism, and NNK metabolism for the one variant (Arg/Cys) was similar to that for other subjects. Although results do not support CYP2A13 or CYP2A6 as predominant contributors to NNK bioactivation and detoxification in peripheral lung of all individuals, CYP2A13 may be important in some.

SOLITARY FIBROUS TUMOR OF THE ANTERIOR MEDIASTINUM: A RARE EXTRAPLEURAL NEOPLASM

Preoperative steroid use has been considered a contraindication to heart-lung as well as lung transplantation. Moreover, most centers delay prednisone administration until 2 to 3 weeks postoperatively until airway healing is secure. We have performed 19 heart-lung transplantations and four single-lung transplantations since 1983. Five recipients (4 heart-lung, 1 single lung) had received prednisone, 5 to 40 mg daily, for 2 to 10 years preoperatively. All recipients were administered prednisone, 0.5 mg/kg daily, starting on postoperative day 1, with a taper to 0.2 mg/kg daily by 4 weeks. Minnesota antilymphocyte globulin (for 10 days), cyclosporine, and azathioprine were also employed. Bronchoscopy, lavage, and transbronchial biopsies were performed every 2 weeks for 3 months postoperatively. No patient had a serious airway complication; 2 heart-lung recipients, not on prednisone preoperatively, had a minor tracheal slough detected on bronchoscopy that resolved spontaneously. Actuarial survival after heart-lung transplantation is 84% +/- 8% and 69% +/- 16% at 1 year and 2 years, respectively. We conclude that prednisone commencing at a dose of 0.5 mg/kg daily from the first postoperative day is a safe practice after heart-lung transplantation. The long-term use of low-dose prednisone before heart-lung transplantation does not preclude normal tracheal healing. The safety of prednisone before and immediately after single-lung transplantation awaits confirmation by further experience.

Blunt Extraperitoneal Rupture Of The Right Hemidiaphragm

Solitary fibrous tumors are uncommon spindle cell neoplasms originally thought to be restricted to the pleura. We describe a 62-year-old woman who presented with stridor and an anterior mediastinal mass. At thoracotomy, a 10.5 × 6.5 × 5.5 cm, circumscribed, firm mediastinal mass demonstrated no direct cardiac or pulmonary involvement. The tumor consisted of spindle cells organized in a patternless pattern with collagenous stroma and hemangiopericytoma-like vessels. Spindle cells were immunoreactive for CD34, CD99, desmin, vimentin and bcl-2 protein and a diagnosis of mediastinal solitary fibrous tumor was confirmed. The differential diagnosis of mediastinal solitary fibrous tumors is extensive and includes spindle cell thymoma, sarcomatoid carcinoma, malignant mesothelioma, inflammatory myofibroblastic tumor, peripheral nerve sheath tumors and various sarcomas. Despite their rarity in the mediastinum, solitary fibrous tumors can be recognized by their classic patternless morphology and immunophenotypic pattern. Their accurate classification is important, as solitary fibrous tumors are intermediate (rarely metastasizing) neoplasms that require complete surgical excision and long-term clinical follow-up for optimum therapy.

Biotransformation of aflatoxin B1 in human lung

A case of blunt extraperitoneal rupture of the right hemidiaphragm and an accompanying abnormal hepatobiliary scan that revealed the rupture are presented. Associated major injuries, the fact that right-sided ruptures have less immediate herniation, and plugging of the defect by the liver are difficulties that can be encountered in establishing the diagnosis. Most diagnostic tests are not helpful and about half of these ruptures are found at laparotomy or thoracotomy. All should be closed surgically.