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Biomedical subjects

Daniel L Miller

Publications and source records attributed to Daniel L Miller.

25 records · Page 2Linked to original sources

Surgical treatment of non-small cell lung cancer 1 cm or less in diameter.

BACKGROUND: Routine lung cancer screening does not currently exist in the United States. Computed tomography can detect small cancers and may well be the screening choice in the future. Controversy exists, however, regarding the surgical management of these small lung cancers. METHODS: The records of all patients were reviewed who underwent resection of solitary non-small cell lung cancers 1 cm or less in diameter from 1980 through 1999. RESULTS: The study included 100 patients (56 men and 44 women) with a median age of 67 years (range 43 to 84 years). Lobectomy was performed in 71 patients, bilobectomy in 4, segmentectomy in 12, and wedge excision in 13. Ninety-four patients had complete mediastinal lymph node dissection. The cancer was an adenocarcinoma in 48 patients, squamous cell carcinoma in 26, bronchioloalveolar carcinoma in 19, large cell carcinoma in 4, adenosquamous cell carcinoma in 2, and undifferentiated in 1. Tumor diameter ranged from 3 to 10 mm. Seven patients had lymph node metastases (N1, 5 patients; N2, 2 patients). Postsurgical stage was IA in 92 patients, IB in 1, IIA in 5, and IIIA in 2. There were four operative deaths. Follow-up was complete in all patients and ranged from 4 to 214 months (median 43 months). Eighteen patients (18.0%) developed recurrent lung cancer. Overall and lung cancer-specific 5-year survivals were 64.1% and 85.4%, respectively. Patients who underwent lobectomy had significantly better survival and fewer recurrences than patients who had wedge excision or segmentectomy (p = 0.04). CONCLUSIONS: Because recurrent cancer and lymph node metastasis can occur in patients with non-small cell lung cancers 1 cm or less in size, lobectomy with lymph node dissection is warranted when medically possible.

Adult↗

Subsequent pulmonary resection for bronchogenic carcinoma after pneumonectomy.

BACKGROUND: Patients who have undergone a pneumonectomy for bronchogenic carcinoma are at risk of cancer in the contralateral lung. Little information exists regarding the outcome of subsequent lung operation for lung cancer after pneumonectomy. METHODS: The records of all patients who underwent lung resection after pneumonectomy for lung cancer from January 1980 through July 2001 were reviewed. RESULTS: There were 24 patients (18 men and 6 women). Median age was 64 years (range, 43 to 84 years). Median preoperative forced expiratory volume in 1 second was 1.47 L (range, 0.66 to 2.55 L). Subsequent pulmonary resection was performed 2 to 213 months after pneumonectomy (median, 23 months). Wedge excision was performed in 20 patients, segmentectomy in 3, and lobectomy in 1. Diagnosis was a metachronous lung cancer in 14 patients and metastatic lung cancer in 10. Complications occurred in 11 patients (44.0%), and 2 died (operative mortality, 8.3%). Median hospitalization was 7 days (range, 2 to 72 days). Follow-up was complete in all patients and ranged between 6 and 140 months (median, 37 months). Overall 1-, 3-, and 5-year survivals were 87%, 61%, and 40%, respectively. Five-year survival of patients undergoing resection for a metachronous lung cancer (50%) was better than the survival of patients who underwent resection for metastatic cancer (14%; p = 0.14). Five-year survival after a solitary wedge excision was 46% compared with 25% after a more extensive resection (p = 0.54). CONCLUSIONS: Limited pulmonary resection of the contralateral lung after pneumonectomy is associated with acceptable morbidity and mortality. Long-term survival is possible, especially in patients with a metachronous cancer. Solitary wedge excision is the treatment of choice.

Adenocarcinoma↗

Completion pneumonectomy: factors affecting operative mortality and cardiopulmonary morbidity.

BACKGROUND: The purpose of this report is to analyze preoperative and perioperative factors affecting operative mortality and cardiopulmonary morbidity after a completion pneumonectomy. METHODS: We retrospectively reviewed all patients who underwent completion pneumonectomy from January 1985 through September 1998 at the Mayo Clinic in Rochester, MN. Factors affecting operative mortality and postoperative morbidity and were analyzed using univariate and multivariate analysis. RESULTS: There were 115 patients (73 men and 42 women), with a median age of 64 years (range, 12 to 83 years). Indication for pneumonectomy was benign disease in 57 patients (49.6%), lung cancer in 51 (44.3%) and metastatic disease in 7 (6.1%). There were 24 deaths (mortality 20.9%, 95% CI 13.9% to 29.4%). Mortality for patients undergoing completion pneumonectomy for benign disease, lung cancer, and metastatic cancer was 26.3%, 17.6%, and 0%, respectively (p = 0.24). Factors adversely affecting mortality with univariate analysis included advanced age (p = 0.004), preoperative corticosteriod use (p = 0.01), decreased preoperative diffusion capacity of lung to carbon monoxide (p = 0.01), intraoperative blood transfusion (p = 0.04), and excessive crystalloid infusion within the first 12 hours (p = 0.01) and 24 hours (0.03) postoperatively, respectively. Factors adversely affecting mortality with multivariate analysis included advanced age (p = 0.001), preoperative corticosteriod use (p = 0.002), and low preoperative hemoglobin (p = 0.02). Cardiopulmonary complications occurred in 72 patients (63.7%). Factors adversely affecting morbidity with univariate analysis included benign disease (p = 0.002), decreased preoperative diffusion capacity of lung to carbon monoxide (p = 0.04), bronchial stump reinforcement (p = 0.0001), and excessive crystalloid infusion within the first 12 hours (p = 0.006) and 24 hours (p = 0.02) postoperatively, respectively. Factors adversely affecting morbidity with multivariate analysis included advanced age (p = 0.005) and bronchial stump reinforcement (p = 0.001). CONCLUSIONS: Multiple factors adversely affect operative mortality and cardiopulmonary morbidity after completion pneumonectomy. Although completion pneumonectomy remains a high-risk procedure, especially for benign disease, it still should be considered a treatment option in selected patients.

Adolescent↗

Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes.

PURPOSE: Survival of lung cancer patients has been dismal. Glutathione enzymes are directly involved in the metabolism of platinum compounds, a group of important chemotherapeutic drugs in cancer treatment. We tested the hypothesis that genes encoding glutathione enzymes may predict lung cancer short-term survival. METHODS: We studied DNA polymorphisms of 250 primary lung cancer patients at four glutathione-related loci: GSTP1, GSTM1, GSTT1 and gamma-GCS that encode glutathione-S-transferase-pi, glutathione-S-transferase-mu, glutathione-S-transferase-theta, and gamma-glutamylcysteine synthetase, respectively. Pearson's chi(2)-square tests, Kaplan-Meier survival curves, log rank tests, and Cox regression models were applied in the analysis. RESULTS: There were 150 (60%) men and 100 (40%) women in this study. Seventeen percent of the patients had never smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their lung cancer diagnosis. Among never smokers, those with null (N) or low (L) genotype experienced a better 1-year-survival rate than those with a positive (P) or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared with patients with N or L at one or both loci (other). Among never smokers, 1-year-survival rates were 60-78% for patients with PP or PH genotypes compared with 89-100% for other types. The survival advantage was greater among advanced-stage patients who were NL or NN than low-stage patients. Similar results were not observed among smokers. CONCLUSIONS: Glutathione-related genes may determine lung cancer survival. Our results, if confirmed, would suggest new directions to enhance cancer treatment, and provide easily measurable markers for clinicians to plan patient-specific therapy.

Female↗

Management of the subcentimeter pulmonary nodule.

The most sensitive imaging modality for detection of pulmonary nodules is computed tomography (CT). Advances in radiologic techniques not only increase the number of nodules detected, but also the nodules that are identified are smaller. With increased use of spiral CT for lung cancer screening, there will be more subcentimeter pulmonary nodules (SCPNs) that will require further diagnostic workup. Radiologic evaluation including repeat observational CT or CT contrast enhancement should be performed. Bronchoscopic or needle biopsy of the majority of SCPNs is not practical. VATS is possible for SCPNs but should be performed in a controlled manner to reduce the resection of benign lesions. An SCPN management algorithm is necessary to expedite resection of a malignant lesion and to minimize removal of benign disease.

Carcinoma, Non-Small-Cell Lung↗

Results of en bloc resection for bronchogenic carcinoma with chest wall invasion.

OBJECTIVE: Lung cancer invading the chest wall without lymph node metastasis has recently been downstaged to stage IIb. To validate this reclassification, we reviewed our experience with en bloc lung and chest wall resection for bronchogenic carcinoma. METHODS: From February 1985 to November 1999, 95 en bloc lung and chest wall resections were performed on 94 patients (62 men and 32 women). The median age was 66 years (range, 38-93 years). Pancoast tumors were excluded. Factors that may affect survival were analyzed with univariate analysis, and factors found to be significant univariately were analyzed multivariately to determine whether the significant association remained after adjusting for other significant factors. RESULTS: Presenting symptoms included chest wall pain in 42 patients, cough in 17 patients, and "other" in 16 patients. Twenty patients were asymptomatic. Ninety-two patients were current or former smokers (median pack-years, 50; range, 8-150 pack-years). Seventy-five lobectomies, 12 pneumonectomies, 5 bilobectomies, 2 wedge excisions, and 1 segmentectomy were performed. The number of ribs resected ranged from 1 to 5 (median, 3). Sixty-one patients required chest wall reconstruction (prostheses in 60 and bovine pericardium in 1). Operative morbidity and mortality were 44.2% and 6.3%, respectively. Sixty-five cancers were classified as T3 N0 M0, 16 as T3 N1 M0, and 14 as T3 N2 M0. Squamous cell carcinoma was present in 56 tumors, adenocarcinoma in 25, large cell carcinoma in 11, and "other" in 3. Follow-up was complete in 86 (96.6%) of 89 operative survivors and ranged from 1 month to 15 years (median, 19 months). Overall 5-year actuarial survival was 38.7%. Five-year survival for patients with stage IIb disease (T3 N0 M0) was 44.3% compared with only 26.3% for those with stage IIIa disease (T3 N1 M0 or T3 N2 M0, P =.0082). Women had a better 5-year survival than men (52.9% vs 31.0%, P =.0122). The best 5-year survival was observed in women with stage IIb disease (61.2%). All other variables (age, tumor size, histopathology, forced expiratory volume in 1 second, extent of operation, depth of invasion, and adjuvant therapy) did not significantly affect survival. CONCLUSIONS: En bloc resection of lung cancer invading the chest wall is safe but associated with significant morbidity. Long-term survival is stage and sex dependent. The best survival is observed in women who have T3 N0 M0 disease (stage IIb).

Adenocarcinoma↗

Paraneoplastic dysmotility: loss of interstitial cells of Cajal.

Autoimmune impairment and destruction of the enteric nervous plexus are thought to play a central role in the pathogenesis of paraneoplastic motility disorders. We present a case of a small-cell lung carcinoma-related paraneoplastic motility disorder associated with abnormal interstitial cells of Cajal networks. Antibodies against c-Kit and protein gene product 9.5 were used to selectively stain interstitial cells of Cajal and the enteric nervous plexus, respectively. A 68-yr-old man presented with anorexia, early satiety, nausea, and weight loss. Investigations revealed gastroparesis, delayed small intestinal transit, and mediastinal lymphadenopathy. The patient was seropositive for type 1 antineuronal nuclear autoantibody and P/Q-type calcium channel antibody. Biopsy of mediastinal lymph nodes revealed metastatic small-cell carcinoma cells that were immunoreactive for c-Kit. Immunohistochemical staining of a full-thickness small intestinal biopsy revealed a relatively intact myenteric plexus but a sparse and disorganized interstitial cells of Cajal network. The histopathology of this case suggests that interstitial cells of Cajal may be a target in the pathogenesis of paraneoplastic motility disorders.

Aged↗