Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.     

Volumetric analysis of tumor extent in nasopharyngeal carcinoma and correlation with treatment outcome

PURPOSE: To investigate the variability of tumor volume in nasopharyngeal carcinoma using quantitative measurements of tumor bulk derived from computed tomography, and to study the prognostic value of tumor volume in comparison with other variables. METHODS AND MATERIALS: Two hundred ninety patients with newly diagnosed nasopharyngeal carcinoma were included in the study. The primary tumor volume (PTV) and nodal tumor volume (NTV) were obtained by outlining the tumor contour followed by summation of areas in sequential pretreatment computed tomography axial scans. Total tumor volume (TTV) was obtained by adding the PTV and NTV. All patients had radiotherapy as the primary treatment, 67 patients also received cisplatin-based neoadjuvant chemotheraphy. RESULTS: A large variation in tumor volume was observed, especially in advanced stage disease. The median PTV (cc) in Ho's T1, T2, and T3 disease were: 6.9 (range: 0.9-42.7), 18.8 (1.6-127.9), and 52.4 (3.3-166.8). The median TTV (cc) in Ho's stage I to IV disease were: 7.6 (range: 1.3-42.7), 19.8 (3.2-55.7), 40.7 (4.1-222.7), and 51.1 (3.1-274.7). Patients with a large PTV (>60 cc) were associated with significantly poorer local control (5-year local control rate: 56%) and disease-specific survival (5-year survival rate: 53%). In patients with a small PTV (< or =20 cc), there were no significant differences in local control among different T stages. Large NTV (>30 cc) was associated with significantly higher distant failure rate (5-year distant relapse-free survival rate: 54%) and lower disease-specific survival (5-year survival rate: 40%). In multivariate analysis, only PTV was found to be an independent factor in predicting local control. CONCLUSION: A large variation of tumor volume was present in different T stage disease of nasopharyngeal carcinoma, and PTV represents an independent prognostic factor of local control that appears to be more predictive than Ho's T stage classification.     

Detailed cytogenetic study of a metastatic bronchial carcinoma

A study of the pre-operative condition of seventy-five hands afflicted with Dupuytren's contracture is followed by an analysis of the results of limited fasciectomy approached by midlateral digital and transverse palmar excisions. The palmar wounds were left open and healing occurred with minimal complications. The correction of contractures compares favourably with that achieved using other techniques of access and wound closure.     

A multiparametric computer analysis of carcinoma of the colon

From 1957 to 1973, 656 patients with carcinoma of the entire colon, excluding those with carcinoma of the rectum, were reviewed with the aid of a computer. Of 457 patients, 69.7 per cent were observed for a minimum of five years. Sixty-five per cent of the lesions were located in the cecum or sigmoid colon. In patients with type A lesion, the five year plus survival rate was 71.15 per cent while, in patients with type D lesions, the five year plus survival rate was zero per cent. Patients who presented with intestinal obstruction had a significantly lower five year survival rate. Roentgenographic visualization of the cecum was significantly less accurate in demonstrating carcinoma when compared with that of the sigmoid colon. An emergency surgical procedure had a significantly higher operative mortality than did elective procedures. In both groups of patients undergoing emergency and elective operations, primary resection and anastomosis led to similar operative mortality rates, although staged procedures resulted in the lowest operative mortality in both groups. In the group of patients who had elective operations, resection an primary anastomosis led to a significantly lower wound infection and fistula rate when compared with the group of patients who had emergency procedures. In comparison with other series, no improvement in survival was illustrated in patients with carcinoma of the colon. The use of new modalities of adjuvant therapy, such as radiotherapy or chemotherapy, or both, actually should be evaluated.     

Computer-based image analysis of nucleoli in prostate carcinoma

The authors have evaluated the nucleoli in 37 cases of prostatic carcinoma. The increase in Gleason's grade 1 correlated with an increase in the percentage of nucleolated nuclei. The increase in the percentage of bi- and trinucleolated nuclei was accompanied by a decrease of the uninucleated nuclei. The values of morphometrical parameters studied in the individual nucleoli (area, perimeter, diameters) increased in Gleason grade 2 tumors as compared with grade 1 tumors. In tumors higher grades there was, however, a progressive decrease of these values.     

Phase II study: concurrent chemo-radiotherapy in advanced nasopharyngeal carcinoma

Oesophageal carcinoma is a major cause of cancer death in certain parts of the world. Early detection provides the only chance of cure. In this study, one female and nine male patients with superficial oesophageal carcinoma were investigated to determine the pertinent clinical and pathological features. All male patients were smokers and six patients drank various amounts of alcohol on a daily basis. Histologically, five cases were confined within the mucosal layer and five within the submucosal layer. All five mucosal cancer cases and two of the five submucosal cancer cases were asymptomatic. Endoscopically, all five mucosal cancer patients had flat lesions, whereas the five submucosal cancer tumours appeared either protruding or depressed. Barium oesophagography failed to demonstrate the lesions in four of five mucosal cancer and one of five submucosal cancer cases. Endoscopic ultrasonography correctly detected the depth of cancer invasion in six out of eight superficial oesophageal carcinoma cases. All patients received a one-stage operation that included oesophagectomy and lymph node dissection. All five mucosal cancer patients had no lymph node involvement and have experienced no tumour recurrence. Among them, one who had concomitant hepatocellular carcinoma died early. Of the five submucosal cancer cases, four died 1-5 years after the operation. It is concluded that oesophageal carcinoma is curable in its early stage. Physicians should be alert while performing endoscopic examination. We believe that the dyeing technique is a useful adjunct to endoscopic examination.     

Reproducibility study of left ventricular measurements with breath-hold cine MRI using a semiautomated volumetric image analysis program

Measurement of exhaled nitric oxide (NO) may allow noninvasive assessment of inflammatory disease in the lung. We determined immediate and day-to-day reproducibility of single-breath NO measurements at different points on the exhaled test, and whether levels recorded reflect levels of NO in the lower airways. Using a rapid chemiluminescence analyser, 55 healthy control subjects performed three sequential tests on each of two days. NO levels were compared at the level corresponding with: 1) the time the mouth pressure fell below 4 cmH2O (MP); 2) the plateau of end-exhaled CO2 (CO2); and 3) the NO plateau (NOp). NO levels were measured directly from the lower airways of 15 lung transplant recipients and compared with NO levels from a single-breath test performed in the same cohort. For measurements performed at MP, CO2 and NOp, the mean +/- SD differences between the two closest levels performed on the same day were 0.11+/-0.18, 0.095+/-0.16 and 0.094+/-0.13 parts per billion (ppb), respectively, and between days were 0.18+/-0.76, 0.19+/-0.78 and 0.17+/-0.8 ppb, respectively. End-expiratory levels recorded at the mouth from a single-breath test and in the lower airways were highly correlated (mouth versus trachea r2=0.95, p<0.0001, mouth versus bronchus r2=0.92, p<0.0001). Single-breath exhaled nitric oxide levels are a simple, reproducible and valid measure of nitric oxide production from the lower respiratory tract.     

Role of Epstein-Barr virus in fine-needle aspirates of metastatic neck nodes in the diagnosis of nasopharyngeal carcinoma

The crystal structure of the peptide Boc-Phe-Val-OMe determined by X-ray diffraction methods is reported in this paper. The crystals grown from aqueous methanol are orthorhombic, space group P2(1)2(1)2(1),a = 11.843(2), b = 21.493(4), c = 26.676(4) A3 and V = 6790 A3. Data were collected on a CAD4 diffractometer using MoK alpha radiation (lambda = 0.7107 A) up to Bragg angle theta = 26 degrees. The structure was solved by direct methods and refined by a least-squares procedure to an R value of 6.8% for 3288 observed reflections. There are three crystal-lographically independent peptide molecules in the asymmetric unit. All the three molecules exhibit extended conformation. The sidechain of the Val2 residue shows two different conformations. The conformation of the peptide Boc-Phe-Val-OMe is compared with the conformation of Ac-delta Phe-Val-OH. It is observed that while Boc-Phe-Val-OMe exhibits an extended conformation, Ac-delta Phe-Val-OH shows a folded conformation. The results of this comparison highlight the conformation constraining property of the delta Phe residue. Interestingly, even though Boc-Phe-Val-OMe and Ac-delta Phe-Val-OH are conformationally different, they exhibit similar packing patterns in the solid state.     

Pathological study on the metastatic routes of bile duct carcinoma

Multiple staining was performed on resected tumors. Samples after curative surgery in 40 cases of bile duct carcinoma for observation of tumor blood vessel density (TVD), and perineural invasion index (PNI). Lymphatic invasion was found in 29 cases (72.5%), blood vessel invasion in 31 (77.5%), and PNI in 33 (82.5%). TVD and PNI were positively correlated with metastasis. Three years after operation, the recurrent rate was 100%, with an averaging recurrent time of 9.6 months in the metastatic group in contrast to 64.3% and 17.5 months in those without metastasis.     

Optimization of prostate biopsy strategy using computer based analysis

PURPOSE: We evaluated and optimized the detection of cancer by prostate biopsies. We developed a stochastic computer simulation model of ultrasound guided biopsies using mathematically reconstructed radical prostatectomy specimens. Use of this technique allows rapid evaluation of a variety of factors for their effect on prostate biopsy results. We used this model to analyze the effectiveness of sextant biopsies, which have been widely adopted in clinical practice. We also analyzed other biopsy schemes. MATERIALS AND METHODS: A total of 607 tumor foci from 180 serially sectioned whole mount radical prostatectomy specimens was mapped and digitized. The cancers had been clinically diagnosed by a variety of biopsy strategies. Simulated parasagittal sextant biopsies were performed for each case. Forty simulation runs (each consisting of a set of 6 biopsies) were performed for each prostate, with realistic random variations in sextant biopsy localization programmed in each run. Cancer detection by biopsy was considered reliable if 90% of the simulation runs for each prostate were positive for cancer. A summary algorithm was used to map the tumor foci. RESULTS: Simulation of sextant biopsies demonstrated reliably detected cancer in only 107 of 147 patients (73%) in whom total tumor volume was greater than 0.5 cc. There was little correlation between total length of cancer in biopsy cores and tumor volume. Change of biopsy angle from 30 to 45 degrees did not result in significantly increased detection rates. Similarly, placing all biopsies more laterally did not increase overall detection rates. When we mapped tumor foci from the 40 cases in which sextant biopsies did not reliably detect tumor, we found that the foci were distributed in areas not biopsied by the sextant method, that is the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone. A 10-core biopsy scheme incorporating these areas as well as the posterolateral prostate reliably detected cancer in 141 of 147 patients (96%) with total tumor volumes greater than 0.5 cc. CONCLUSIONS: Prostate cancer of significant volume can be present in areas not sampled by standard sextant biopsies. Biopsies of the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone should be considered for re-biopsy strategy after negative sextant biopsies. Sampling of these additional areas also can be incorporated in an initial biopsy scheme to increase overall initial rates of detection of prostate cancer.     

Surgical analysis for metastatic lung tumor from renal cell carcinoma

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.     

Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and cisplatin for locally advanced and metastatic/recurrent undifferentiated carcinoma of the nasopharyngeal type

PURPOSE: This article presents an assessment of the combination of bleomycin, epirubicin, and cisplatin as induction chemotherapy before radiotherapy in the treatment of undifferentiated carcinoma of the nasopharyngeal type in patients with recurrent/metastatic disease (group A), and in previously untreated patients with locoregionally advanced disease (UICC-AJCC 87, N2-3, M0) (group B) in terms of toxicity, antitumoral activity, and therapeutic efficacy. PATIENTS AND METHODS: From January 1987 to September 1990, 111 consecutive patients with histologically proven UCNT were treated with six cycles of intravenous cisplatin (100 mg/m2 day 1) epirubicin (80 mg/m2 day 1), and bleomycin (15 mg bolus day 1), followed by 16 mg/m2/day continuous infusion for 5 days, repeated every 21 days for three cycles. Three further cycles without bleomycin were given to 44 patients in group A. In group B (67 patients), only three cycles of the same protocol were given, with a slightly lower dose of epirubicin (70 mg/m2), followed by conventional radiotherapy (70 Gy/7 weeks). RESULTS: Of 44 patients entered in group A, 38 were evaluable for response. We observed 9 (20%) complete responses and 11 (25%) partial responses, for a 45% overall response rate. In 12 patients not previously given chemotherapy, there were 4 complete responses, compared to 5 complete responses in 32 patients previously treated with chemotherapy. Four patients are alive with no evidence of disease after 53+, 60+, 61+, and 72+ months. In group B the overall response rate to chemotherapy was 98% with 42 complete (62%) and 24 partial responses (36%). Three months after the end of radiotherapy, the overall complete response rate was 94% (63 patients). After a median follow-up time of 77 months (range, 53-94), the 4-year overall survival and disease-free survival rates for this group are 66% and 60%, respectively. The median disease-free survival has not been reached at 90 months. CONCLUSION: The results of the BEC combination trial are very encouraging in metastatic and recurrrent UCNT, with durable remissions in this poor-prognosis population. The results in patients with locally advanced disease have motivated prospective phase III testing of the neoadjuvant chemotherapy approach to evaluate its impact on locoregionally advanced disease (> or =N2MO UICC-AJCC 87).     

Unusual endocrine presentations of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma is endemic in Southern China and the majority of patients present with local symptoms due to the tumor. METHODS: This report describes two unusual cases of occult nasopharyngeal carcinoma in which the patients initially presented with endocrine manifestations. RESULTS: The first patient presented with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production. Nasolaryngoscopy showed a growth in the left nasal fossa and biopsy revealed a poorly differentiated nasopharyngeal carcinoma that exhibited positive immunostaining for ACTH. The second patient presented with a 10-month history of bone pain over both lower limbs. She was normocalcemic but her serum alkaline phosphatase was markedly elevated. A bone biopsy showed both osteoclastic and osteoblastic activity with widespread fibrosis suggestive of Paget's disease. Three months later, she developed third cranial nerve palsy. Computed tomography investigation revealed a soft tissue mass filling the sphenoid and ethmoid sinuses. Biopsy showed a poorly differentiated nasopharyngeal carcinoma. The bone biopsy was reviewed and immunohistochemistry demonstrated the presence of cells positive for the epithelial marker AE1/3 within the fibrous stroma. Radio-labeled in situ hybridization showed that Epstein-Barr virus early RNA was present in these tumor cells and the bone lesions were in fact metastases. CONCLUSIONS: Nasopharyngeal carcinoma can present with rather atypical symptoms that may lead to a delay in diagnosis. Therefore, in high risk populations, it is important to consider nasopharyngeal carcinoma as a possible primary tumor in patients with occult carcinomas.     

Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients

BACKGROUND: Patients with neuroendocrine carcinoma often present with liver metastases not amenable to hepatic resection. For them, liver transplantation has been considered a viable treatment option, especially if hormonal symptoms and pain cannot be controlled medically. Still, little is known regarding potential prognostic factors and long-term survival after liver transplantation for neuroendocrine tumors. METHODS: A search of English, French, and German literature identified patients with liver transplantation for extensive metastases from neuroendocrine carcinoma for whom follow-up data were available. RESULTS: Overall, 2-year and 5-year survival for all 103 patients was 60% and 47%, respectively, but recurrence-free 5-year survival did not exceed 24%. Univariate analysis identified age less than 50 years, primary tumor location in lung or bowel, and pretransplant somatostatin therapy as favorable prognostic factors, whereas extended operations combining liver transplantation with upper abdominal exenteration or Whipple's procedure were associated with poor prognosis. Multivariate analysis identified age greater than 50 years (P<0.03) and transplantation combined with upper abdominal exenteration or Whipple's operation (P<0.001) as adverse prognostic factors. CONCLUSIONS: Liver transplantation may be justified in selected patients to provide immediate relief of otherwise intractable pain or hormone-related symptoms. Transplantation with curative intent appears worthwhile in young patients with only hepatic disease. In older patients with extrahepatic disease requiring extended operations, long-term results are discouraging, and the small benefit achieved by liver transplantation must be weighed against medical treatment options and the natural course of often slowly progressing disease.     

Primary tubal carcinoma: a retrospective analysis of four cases with a literature review

This paper comprises a brief examination of the concept of process recording and its current applications in nursing and health-related professions. The possible benefits and problems of using the process recording tool as a summative assignment method within a nursing diploma course will be discussed in the light of experience at one former college of health in the North of England. The author argues that the process recording assignment offers a useful means of relating communication theory to practice and an opportunity for students to engage in reflection on their practice in a structured way.     

Preservation of tubal function in patients with nasopharyngeal carcinoma, post-irradiation

Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian tube function testing before and 5 years after irradiation. Tubal patency and clearance function of the eustachian tube showed deterioration if maximum irradiation dosage was more than 70 Gy, whereas dynamic function of the eustachian tube was preserved. Development of middle ear complications in NPC patients post-irradiation was caused by both tubal and inflammatory factors. To preserve tubal function, maximum irradiation dosage to NPC should be limited to 70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should be drained by repeated myringotomies instead of grommet insertion, and secondly, sinusitis should be evaluated and treated, because sinusitis can aggravate otitis media with effusion.