Dynamics of secondary contamination from the interaction of high-power laser pulses with metal particles attached on the input surface of optical components.

We investigate the interaction of 355-nm and 1064-nm nanosecond laser pulses with nominally spherical metallic particles dispersed on the input surface of transparent substrates or high-reflectivity (HR) multilayer dielectric coatings, respectively. The objective is to elucidate the interaction mechanisms associated with contaminant-induced degradation and damage of transparent and reflective optical elements for high-power laser systems. The experiments involve time-resolved imaging capturing the dynamics of the interaction pathway, which includes plasma formation, particle ejection, and secondary contamination by droplets originating from the liquefied layer of the particle. The results suggest that HR coatings are more susceptible to secondary contamination by liquid droplets produced by the particles because of the different geometry of excitation and the location of plasma initiation. Modeling results focus on better understanding the melting of the particle surface, leading to ejections of liquid droplets and the pressure applied to the substrate, leading to mechanical damage.

Impact of laser-contaminant interaction on the performance of the protective capping layer of 1 ω high-reflection mirror coatings.

High dielectric constant multilayer coatings are commonly used on high-reflection mirrors for high-peak-power laser systems because of their high laser-damage resistance. However, surface contaminants often lead to damage upon laser exposure, thus limiting the mirror's lifetime and performance. One plausible approach to improve the overall mirror resistance against laser damage, including that induced by laser-contaminant coupling, is to coat the multilayers with a thin protective capping (absentee) layer on top of the multilayer coatings. An understanding of the underlying mechanism by which laser-particle interaction leads to capping layer damage is important for the rational design and selection of capping materials of high-reflection multilayer coatings. In this paper, we examine the responses of two candidate capping layer materials, made of SiO2 and Al2O3, over silica-hafnia multilayer coatings. These are exposed to a single oblique shot of a 1053 nm laser beam (fluence ∼10 J/cm2, pulse length 14 ns), in the presence of Ti particles on the surface. We find that the two capping layers show markedly different responses to the laser-particle interaction. The Al2O3 cap layer exhibits severe damage, with the capping layer becoming completely delaminated at the particle locations. The SiO2 capping layer, on the other hand, is only mildly modified by a shallow depression. Combining the observations with optical modeling and thermal/mechanical calculations, we argue that a high-temperature thermal field from plasma generated by the laser-particle interaction above a critical fluence is responsible for the surface modification of each capping layer. The great difference in damage behavior is mainly attributed to the large disparity in the thermal expansion coefficient of the two capping materials, with that of Al2O3 layer being about 15 times greater than that of SiO2.

Analysis of a pathology review of patients with lung tumors.

The rates of agreement and patterns of disagreement in the classification of lung tumors were evaluated for a pathology panel review of 476 patients with lung cancer. The panel review consisted of three independent diagnoses made in accordance with the criteria of the Working Party for Therapy of Lung Cancer. At least two of the three pathologists agreed as to the major cell classification in 94% of the patients. In 67% of the evaluations, there was agreement among the three pathologists. Small-cell carcinoma and epidermoid carcinoma were the most consistently evaluated classes, followed by adenocarcinoma and large-cell carcinoma. The poorly differentiated categories provided the greatest source of difficulty in discriminating among major histologic classes. For an initial diagnosis of large-cell carcinoma, 14% of the second classifications were poorly differentiated epidermoid carcinoma, and 20% were poorly differentiated adenocarcinoma. For an initial diagnosis of small-cell carcinoma, 11% of the second independent evaluations classified the carcinoma as other than small-cell. The most likely alternative diagnosis was large-cell carcinoma (5%).

Influence of histologic subtype of small cell carcinoma of the lung on clinical presentation, response to therapy, and survival.

Patients with small cell carcinoma of the lung (SCCL) were histologically subtyped according to the Working Party for Therapy of Lung Cancer classification and were treated with combination chemotherapy. Of the 103 patients studied, 54 had the lymphocyte-like (oat cell) subtype, 41 had the intermediate cell subtype, and 8 had a mixture of the two. No significant difference in initial performance status, extent of disease, chemotherapeutic response rate, or survival (median, 10.2 mo) was noted among the histologic subtypes. When the histologic subtype of the primary biopsy tissue was compared with the subtype of other pathology specimens from the same patient, concordance of subtype was present in 74% of the patients. In the remaining 26%, two or three histologic subtypes were present. This study demonstrates no clinically significant differences among the various histologic subtypes of SCCL in patients extensively staged and treated with aggressive cytotoxic therapy. Because of this and because concurrent biopsy tissues from multiple sites in the same patient may vary in subtype, we conclude that prognostic or therapeutic decisions should not be based on SCCL subtype.

Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy.

Eight (4%) of 203 consecutive prospectively staged and treated patients with small cell carcinoma (SCC) had no evidence of pulmonary or mediastinal tumor on chest roentgenogram or at fiberoptic bronchoscopy at the time of diagnosis. There were two distinct clinical presentations in these SCC patients with exclusively extrapulmonary tumors. Four had discrete localized extrapulmonary neoplasms, presumably originating in these sites. In the other 4 cases with either regional or widely metastatic disease, no obvious primary tumor could be documented in the lungs or elsewhere. One complete and two partial responses to chemotherapy (duration 6 to greater than 11 mo) occurred in 6 evaluable patients. Two remaining patients were inevaluable for response because they received adjuvant chemotherapy after irradiation or excision of the primary tumor and are free of disease at 15 and 28 months. Results document two clinicopathologic entities of extrapulmonary SCC, more firmly establish that it can be responsive to chemotherapy, and encourage systemic therapy as part of initial treatment planning.

Diagnostic and biological implications of flow cytometric DNA content analysis in lung cancer.

Flow cytometric DNA content analysis, performed on clinical specimens from patients with lung cancer, was compared with clinical features, histological and/or cytological examination of the same specimen and, in some instances, to chromosome analysis and repeat DNA content analysis of short-term cultures. Tumors from 85% of non-small cell and 83% of small cell lung cancer patients had aneuploid DNA content; multiple aneuploid stem lines were present in 11% of patients. Comparisons with microscopic examination showed that aneuploid cells were detected in 122 of 167 clinical samples containing tumor cells and in 3 of 177 samples microscopically free of tumor. The high false-negative rate, shown to be due in large part to the presence of near-diploid tumor cells, makes single-parameter DNA analysis impractical for use in automated cytology. Short-term cultures of tumor cells, used to confirm that tumors had DNA content indistinguishable from diploid, demonstrated a single near-diploid peak on repeat DNA analysis with or without the addition of diploid lymphocytes and internal DNA standards. Chromosome banding studies showed clonal structural abnormalities with minimal numeric alterations. Survival of small cell lung cancer patients was similar for patients with near-diploid and aneuploid tumors. Cell cycle analysis could be performed in only a minority of samples, and there were no apparent differences in the proliferative fraction between lung cancer cell types. We conclude that flow cytometric DNA content analysis provides useful biological information and is a useful marker for following tumor cell cultures, but multiparameter analyses will be required for use in automated cytology and in cell kinetic studies.

Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis.

The clinical course of cutaneous T cell lymphoma (mycosis fungoides and Sezary syndrome) is generally indolent, but in occasional patients becomes fulminant. We found that biopsies from patients with accelerating disease can reveal cytologic transformation from previously observed small, convoluted lymphocytes to large cells that are similar to cells seen in large-cell lymphoma. The cerebriform nuclei characteristic of malignant T cells can only rarely be identified. Of 150 cutaneous T cell lymphoma patients we treated from 1976 to 1984, cytologic transformation was identified in 12 after review of peripheral blood smears and biopsies from skin, lymph nodes, and visceral sites. Patients who developed cytologic transformation were initially characterized by advanced stage (11 of 12), with lymph node effacement (seven of 11) and erythroderma (five of 12). The tumor cell DNA content after transformation was aneuploid (four of four), and the ability to form rosettes with sheep erythrocytes was retained in transformed cells (three of three). The median time from diagnosis of cutaneous T cell lymphoma to cytologic transformation was 21.5 months (range, 4 to 64), and the median survival from transformation was only 2 months (range, 0 to 19+). We conclude that cytologic transformation in cutaneous T cell lymphoma represents a distinct clinicopathologic entity, characterized by an aggressive clinical course.

Diagnosis and significance of liver metastases in small cell carcinoma of the lung.

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.

Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience.

CLM developed in 60 of 526 patients (11%) with SCLC seen at the NCI between August 1969 and June 1980. Life table analysis revealed an overall 25% risk of CLM at 3 years. CLM was diagnosed during all phases of the patients' clinical course, but the majority (83%) were cases diagnosed at the time of progressive systemic disease. Univariate log rank analysis indicated that pretreatment factors associated with the development of CLM included: involvement of the brain, spinal cord, bone marrow, liver or bone; extensive disease; and male sex. Patients who did not obtain a complete response to systemic therapy were at greater risk of developing CLM than complete responders. Multivariate analysis of these factors indicated that liver metastases were most strongly associated with the time to development of CLM, followed in order of importance by bone and CNS metastases. Patients usually presented with signs and symptoms reflecting involvement of multiple areas of the neuraxis including the cerebrum, cranial nerves and spinal cord; 51 of the 60 patients had intracerebral metastases and 27 had spinal cord lesions during their clinical course. Autopsy features including focal or diffuse involvement of the leptomeninges with infiltration of the Virchow-Robin spaces were similar to meningeal lymphoma and leukemia, except that CLM was rarely the sole manifestation of CNS tumor. Median survival following the diagnosis of CLM was 7 weeks. However, most deaths were attributed to systemic disease, and treatment with intrathecal chemotherapy and irradiation often provided palliation. With the increased awareness of this complication, an antemortem diagnosis increased from 39% prior to 1977, to 88% of patients after 1977.

Small cell bronchogenic carcinoma: a distinct clinicopathologic entity.

Since small cell carcinoma is a treatable disease, with surgery being beneficial in a few cases and with chemotherapy, radiotherapy, and immunotherapy contributing to prolonged survival in patients with inoperable disease, it is essential that the clinical and pathologic features of small cell carcinoma be quickly recognized in a newly presenting patient so that appropriate therapy may be offered.

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival.

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival.

Treatment of extensive stage small cell bronchogenic carcinoma. Effects of variation in intensity of induction chemotherapy.

Forty-nine consecutive previously untreated patients with extensive stage small cell bronchogenic carcinoma were treated with cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, etoposide (VP-16-213) 125 mg/m2, and vincristine 1.4 mg/m2 (maximum 2 mg) as induction chemotherapy. Thirty-four patients were given high-intensity therapy, receiving these drugs on both Days 1 and 8 of two or three 21-day induction courses. Fifteen other patients were treated with moderate intensity, receiving these drugs only on Day 1 of two 21-day induction courses. The number and intensity of induction courses were determined by the time of entry into the study. There were 31 complete or partial remissions among the 33 evaluable patients treated with high-intensity therapy (94 percent), including eight complete remissions (24 percent), whereas there were 11 responses (73 percent) including three complete responses (20 percent) among the 15 patients treated with moderate-intensity therapy. There was no marked tendency for the patients in the high-intensity group to have a more favorable response to the induction chemotherapy (p = 0.22), and survival experience was very similar in the two groups (p = 0.92). Overall median survival was 12 months. Within the high-intensity group, there was no significant difference between patients receiving two or three courses of induction therapy with respect to response (p = 0.97) or survival (p = 0.32). There were six induction deaths in the high-intensity induction group (18 percent) and one induction death in the moderate-intensity group (7 percent) (p = 0.59). In addition to the expected hematologic and infectious complications, there were unexpectedly high frequencies of mucositis, reversible congestive heart failure, and severe peripheral neuropathy in patients treated with high-intensity induction. Only two patients, both in the high-intensity group, were alive and free of disease at 24 months. Increasing the intensity of induction chemotherapy with these drugs did not significantly improve response or survival in extensive stage small cell bronchogenic carcinoma.

Non-small-cell lung cancer. Major cause of late mortality in patients with small cell lung cancer.

Among 360 patients with small cell lung cancer treated in National Cancer Institute therapeutic trials from 1973 to 1982, 40 were two-year cancer-free survivors. Of these 40 patients, six had later development of non-small-cell lung cancer at 3.5 to 8.0 years (median 5.1) after the diagnosis of small cell lung cancer. Three had the second malignant tumor in the contralateral lung, one in a different lobe, and two in the same lobe as the initial small cell lung cancer. Ten patients had relapses of small cell lung cancer at 2.1 to 6.2 years (median 3.2) from diagnosis. Three recurrences were in the same site or lobe as the initial lesion, four in the same lobe and in sites outside the thorax, and three solely in sites outside the thorax. It is concluded that these non-small-cell lung cancers usually represent second primary lung tumors and that most late small cell lung cancers represent relapses occurring up to 6.2 years from diagnosis. In this study, the risk of development of non-small-cell lung cancer after two years of disease-free survival following small cell lung cancer is 4.4 percent per person-year, approximately 10 times higher than the rate of 0.5 percent previously determined in screening studies of men at high risk for lung cancer. Non-small-cell lung cancer represents more than a third of lung cancer deaths in patients with small cell lung cancer surviving beyond two years from diagnosis and more than half of lung cancer deaths beyond three years. It is recommended that all patients treated for small cell lung cancer discontinue smoking.

Histologic assessment of lymph nodes in mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): clinical correlations and prognostic import of a new classification system.

Mycosis fungoides and the Sézary syndrome share common cutaneous histopathologic features, and this spectrum of malignant disease is referred to here as cutaneous T-cell lymphoma (CTCL). A method (LN classification) for describing the histopathologic features of lymph nodes in CTCL is presented. In this system, lymph node biopsy specimens are scored according to the number of atypical lymphoid cells in T-cell-dependent paracortical zones and the preservation or distortion of the lymph node architecture. Lymph node architecture is preserved in lymph nodes scored LN1 to LN3, and these nodes may have coexistent dermatopathic change. LN1 nodes have single infrequent atypical lymphocytes in paracortical T-cell regions. LN2 nodes have small clusters of paracortical atypical cells. LN3 nodes have large clusters of atypical cells. LN4 nodes are partially or totally effaced by atypical cells. This system was used to classify 96 lymph node biopsy specimens obtained within six months of the initial diagnosis of CTCL; no LN1 nodes, 37 LN2, 44 LN3, and 15 LN4 nodes were found. The LN class was significantly correlated with the extent of skin, blood, and visceral involvement, as well as with survival. Patients with LN2 lymph nodes have an estimated five-year survival of 70 per cent, while patients with LN3 and LN4 nodes have estimated five-year survivals of 30 and 15 per cent, respectively. The survival differences between the LN subgroups were all significant (P less than 0.05). The LN classification system was clearly shown to be reproducible among experienced pathologists. The LN system for the histopathologic classification of lymph nodes in CTCL is of prognostic value and should be used to assess lymph node biopsies in patients with CTCL.

Cardiac metastases in lung cancer.

Cardiac metastases from bronchogenic carcinoma are not commonly diagnosed prior to death. This study isolates factors associated wtih the development of cardiac involvement. Four hundred eighteen consecutive patients with lung cancer who had autopsies were studied. Twenty-five percent of these patients had cardiac involvement. Factors associated with cardiac metastases were (1) histologic cell type of the tumor, (2) aggressive therapy, (3) extent of disease, and (4) tumor differentiation. The presence of cardiac metatases was not related to the length of survival. Clinical signs of cardiac involvement included an enlarging heart on the chest x-ray film, development of congestive heart failure, or electrocardiographic changes. Suspicion of cardiac metastases in high-risk individuals, prompt diagnostic evaluation, and rapid institution of therapy may improve the outlook for many patients, since reaccumulation of fluid was generally slow.

Surgical resection in the management of small cell carcinoma of the lung.

In an attempt to define the role of initial surgical resection in patients with undifferentiated small cell carcinoma of the lung, we reviewed the experience of the Veterans Administration Surgical Oncology Group (VASOG). One hundred forty-eight patients with small cell carcinoma of the lung had undergone a potentially "curative" resection. This represented 4.7% of "curative" resections carried out in four major prospective adjuvant chemotherapy trials. In the early trials (101 patients), 16 patients (15.8%) died within the first 30 postoperative days. These patients have been excluded from the analysis of long-term survival, since in the more recent trials postoperative deaths were excluded prior to randomization. In the 132 patients remaining, the 5 year survival rate by the life-table method was 23.0%. The tumor of each was classified pathologically by the TNM system. Five-year survival rates for each category were as follows: T1 N0 M0 59.9%, T1 N1 M0 31.3%, T2 N0 M0 27.9%, T2 N1 M0 9.0%, and any T3 or N2 3.6%. The effect of postoperative adjuvant chemotherapy was evaluated in each of the trials. No beneficial effect of the adjuvant therapy was noted with a one or two course regimen of either nitrogen mustard or cyclophosphamide, but possible benefit, although not significant, was noted in a prolonged intermittent chemotherapy trial of cyclophosphamide either alone or alternating with methotrexate. In the most recent trial of prolonged intermittent courses of 1-(2-chlorethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and hydroxyurea, a 5 year survival rate of 80.8% was noted in those receiving adjuvant chemotherapy as compared to a 38.1% in the control group. We conclude that resection is definitely indicated in patients with T1 N0 M0 lesions and probably indicated in those with T1 N1 M0 or T2 N0 M0 lesions. Primary surgical resection is contraindicated in patients with any other TNM category.

Serial fiberoptic bronchoscopy during chemotherapy for small cell carcinoma of the lung: early detection of patients at high risk of relapse.

Serial fiberoptic bronchoscopic examinations were performed during intensive chemotherapy with a combination of drugs in 77 previously untreated patients with small cell carcinoma of the lung. Before treatment, bronchoscopic examination revealed evidence of cancer in 93 percent (70) of the 75 patients studied at that time, including 8 percent (six) in whom the tumor was not evaluable on the chest x-ray film. After therapy was initiated, 36 percent (29) of the 81 procedures performed in patients with a complete response radiographically and 62 percent (33) of the 53 bronchoscopic procedures in those with a partial response or no response showed evidence of tumor. In both of these groups, patients with abnormal findings on endoscopic examination had a much higher rate of relapsing tumor of the chest within a 12-week period. Progression of intrathoracic tumor was first detected solely by bronchoscopic examination in 22 percent (seven) of the 32 episodes of progression. In our hands, repeated fiberoptic bronchoscopic procedures during chemotherapy for small cell carcinoma have yielded information not apparent from the chest x-ray film in a significant number of patients.

Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas.

Bronchial carcinoids and small cell lung cancer (SCLC) are currently recognized as neuroendocrine (NE) neoplasms. However, non-SCLC (NSCLC) may also express NE properties. Paraffin-embedded sections of a comprehensive panel of 113 lung carcinomas were analyzed for the expression of three general markers common to all NE cells, namely, chromogranin A, Leu-7 and neuron-specific enolase (NSE), five specific NE secretory products, and four other tumor markers by immunohistochemistry using the sensitive avidin-biotinylated peroxidase technique. The authors were able to demonstrate the following: (1) most, but not all carcinoids and SCLCs expressed multiple NE markers in a high percentage of tumor cells; (2) up to a half of NSCLC cases contained small subpopulations of cells expressing NE in a high percentage of tumor cells; (2) up to half of NSCLC cases contained small subpopulations of cells expressing NE markers; and (3) occasional NSCLCs showed staining patterns indistinguishable from SCLC. Specifically, 7 of 77 NSCLCs expressed four or more NE markers. NE markers in NSCLCs were more commonly expressed in adenocarcinomas and large cell carcinomas and rarely in squamous cell carcinomas. For comparison, the mean number of NE markers expressed by all cases of NSCLC was 1.5, carcinoids 6.0, and SCLCs 3.8. Individual "marker counts" were not useful in categorizing lung tumors as carcinoids and SCLC versus NSCLC. Instead, 95% of the tumors were correctly classified, applying a statistical model created from staining indices of the three general NE markers (chromogranin A, Leu-7, NSE) and three other tumor markers (carcinoembryonic antigen, keratin, vimentin). Because NSCLCs with NE features might have different clinical characteristics than other NSCLCs, immunohistochemistry provides an effective manner to identify this biologically interesting subset of NSCLCs in routine paraffin sections.

Skeletal manifestations in cutaneous T-cell lymphomas.

The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. Hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.

ICRF-159 in advanced gastric cancer. Absence of activity.

ICRF-159, and EDTA derivative antitumor agent, was given to 21 patients with advanced gastric cancer in a weekly dose of 3000 mg/m2. Of the 21 patients, 11 had failed prior drug therapies and 10 were previously untreated. No patient achieved an objective partial response (actual response less than 15% with 95% confidence level). One previously treated patient had a minor response lasting 12 weeks and four patients (three previously untreated) had stable disease lasting 4-8 weeks. Toxicity was acceptable, consisting of mild nausea and moderate myelosuppression. Median survival after treatment was 17.5 weeks in previously untreated patients and 9 weeks in previously treated patients. We conclude that ICRF-159 is inactive in advanced gastric cancer when given on a weekly schedule.