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Biomedical subjects

C J Wang

Publications and source records attributed to C J Wang.

At least 19 recordsLinked to original sources
PubMed1999

Postoperative radiotherapy in early stage carcinoma of the uterine cervix: treatment results and prognostic factors.

PURPOSE: The objective was to investigate the effect of pathologic parameters and other variables on treatment outcome for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA cervical carcinoma, as well as to assess the morbidities attributable to radical surgery combined with postoperative radiotherapy. MATERIALS AND METHODS: Between January 1980 and June 1994, 179 women with FIGO stage IB, IIA carcinoma of the uterine cervix were treated with radical hysterectomy and postoperative irradiation. The median follow-up of alive patients was 6.8 years. All patients received 44-60 Gy external irradiation. One hundred fifty-nine patients received 3-10 Gy intracavitary brachytherapy. The data were analyzed for overall survival, disease-free survival, pelvic control, and treatment-related complications. RESULTS: The 5-year overall survival rate, disease-free survival rate, and pelvic control rate for the 179 patients were 72, 74, and 90%, respectively. The 5-year overall survival rate was 81% for patients without pelvic lymphadenopathy and 53% for those with pelvic lymphadenopathy (P = 0.0000). Other independent prognostic factors for overall survival included tumor differentiation and the interval between operation and initiation of radiotherapy. For the endpoint of disease-free survival, pelvic lymph node status, tumor differentiation, the duration of interruption of radiotherapy, and the interval between operation and radiotherapy were of independent prognostic significance. As pelvic control was concerned, the 5-year pelvic control rate was 90% and only the duration of interruption of radiotherapy was noted as an independent predictor of pelvic control. Distant metastases were noted in 43 patients (24%); the most common sites were lung (10%), liver (6%), and bone (6%). The overall 5-year intestinal and urinary complication-free rate was 66 and 82%, respectively. The overall incidence of grade 3 or above late rectal and urinary sequelae was 10%. For patients sustaining leg lymphedema after radiotherapy, there was higher incidence of severe leg cellulitis which warranted antibiotics treatment. CONCLUSION: These prognostic factors should be considered in patient counseling and treatment planning. Based on these factors, a more aggressive treatment to improve survival in these subsets of high-risk patients might be justified. New therapeutic regimens and modalities aimed to overcome treatment failure should be investigated.

Adenocarcinoma↗
PubMed1999

Recalcitrant bicipital radial bursitis.

Three of 12 nonrheumatoid patients with bicipital radial bursitis had recurrent and recalcitrant symptoms and underwent operative treatment. Preoperative computed tomogram showed an anterior distended synovial cyst at the level of the radial tubercle. Magnetic resonance imaging provided a superb demonstration of a bicipital radial bursa which communicated with the elbow joint below the annular ligament. Surgical exploration revealed a valvular mechanism between the distended bursa and the joint cavity. Excision of the distended bursa and closing the capsular defect lead to excellent results. An antecubital cyst resulting from an acute or chronic tear of the anterior capsule at the sacciform recess may communicate with the bicipital radial bursa and become the cause of recurrent and recalcitrant symptoms.

Adult↗
PubMed1999

Cell surface markers and circulating cytokines in graft versus host disease.

Graft versus host disease (GVHD) remains the major obstacle to the widespread application of allogeneic bone marrow transplantation (BMT) despite improvement in drug prophylaxis. T cells in the donor bone marrow recognize and react against host alloantigens and thereby initiate GVHD, but the precise mechanisms by which host tissues are damaged remain unclear. In the current study, we determined the cytokine secretion, cell population distribution, and cell surface markers expression by ELISA and flow cytometer, to understand further the pathophysiology of GVHD. Our results demonstrated that there was no significant change in the cell ratio of B-and T- lymphocytes, and helper/suppressor cells during GVHD development when compared to the condition before transplantation. Furthermore, the percentage of natural killer cells, the interleukin-2 receptor (IL-2R) or the HLA-DR antigen on both CD4 and CD8 positive cells presented no significant difference between pre-transplantation and during GVHD. The serum cytokine secretion of IL-1, TNF-alpha, IL-2, ICAM-1, endothelin, TGF-beta showed no difference before BMT and during GVHD. However, when patients in the developing of GVHD, there was significant difference in the serum levels of soluble IL-2R (slL-2R), epidermal growth factor (EGF), and platelet derived growth factor (PDGF). In addition, with patients who develop GVHD, the mixed lymphocyte reaction also presented a significant difference. This study indicated that some serum cytokines such as sIL-2R, growth factors, and the mixed lymphocyte reaction may be used as parameters for the early detection of the development of GVHD.

Adolescent↗
PubMed1998

Local vaginal anesthesia during high-dose-rate intracavitary brachytherapy for cervical cancer.

PURPOSE: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. METHODS AND MATERIALS: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. RESULTS: The mean VAS values recorded during the treatment sessions and control sessions were 49.9 +/- 24.1 versus 60.1 +/- 24.8, respectively. The value of VAS in the treatment session was significantly lower than that of the control session (p < 0.001). No statistically significant differences were found in the changes of blood pressure and heart rate and in the incidence of side effects during these two types of sessions (p > 0.05). In the drug-level study, serum levels of lidocaine reached a peak 5 min after the initiation of local anesthesia. The mean peak concentrations (Cmax) of lidocaine were 0.50 +/- 0.45 microg/ml. CONCLUSION: Local vaginal anesthesia with 10% lidocaine solution can significantly decrease the degree of painful sensation during HDR intracavitary brachytherapy, and is safe to administer for the procedure for cervical cancer.

Anesthesia, Local↗
PubMed1998

Tumor promoting effect of N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (a nitrosated Maillard reaction product) in benzo(a)pyrene-initiated mouse skin carcinogenesis.

N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (NO-HNTA) is a product generated in a model browning system in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass, nuclear magnetic resonance and infrared spectroscopy in our study. Twenty weeks, twice weekly, topical application of NO-HNTA at the concentration of 10, 50 and 250 mumol to mice previously initiated with benzo(a)pyrene (B[a]P) increased their tumor formation by 3.2-, 4.6- and 5.8-fold respectively. Application of the same amount of NO-HNTA not only caused significant induction of hyperplasia but also the activity of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with various amounts of NO-HNTA (10, 50 and 250 mumol) caused production of hydrogen peroxide by 1.38-, 1.95- and 3.26-fold respectively, and induction myeloperoxidase (MPO) by 24-, 63- and 102-fold. These results indicate that the formation of NO-HNTA or its derivatives derived from the reaction of tyrosine and glucose in the presence of sodium nitrite has the potential as a tumor promoter.

Animals↗
PubMed1998

Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse skin.

Hibiscus protocatechuic acid (PCA), a phenolic acid isolated from Hibiscus sabdariffa L., was evaluated for its ability to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion in skin tumors of female CD-1 mice. Topical application of PCA (5, 10 or 20 micromol) 5 min prior to TPA (15 nmol) treatment twice weekly for 20 weeks to mice which were initiated with benzo[a]pyrene (B[a]P) inhibited the incidence of tumors in mice to 81.3, 62.5 and 56.3%, respectively, while all mice in the TPA-treated group developed tumors. The average number of tumors in mice pretreated with PCA was 2-4 and that of mice treated only with TPA was 6.6. The protection effects of PCA were also presented by its significant suppression on the TPA-induced hyperplasia in the skin and edema of mouse ears by 65 and 73% at doses of 10 and 20 micromol, respectively. When it was applied to the dorsal surface of CD-1 mice before TPA application, PCA (5, 10 or 20 micromol) inhibited the induction of epidermal ornithine decarboxylase (ODC) activity by 5 nmol TPA and myeloperoxidase (MPO) activity by 6.5 nmol TPA. The same doses of PCA also reduced the formation of hydrogen peroxide in the mouse skin to an inhibition of 61, 84 and 89%, respectively, when compared with that of the TPA-treated group. These results indicate that PCA possesses potential as a cancer chemopreventive agent against tumor promotion.

Animals↗
PubMed1998

Impact of the extent of parametrial involvement in patients with carcinoma of the uterine cervix.

PURPOSE: A scoring system is proposed to measure the extent of parametrial involvement and predict treatment outcome in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: 244 patients with FIGO Stage IIB (n = 146) or IIIB (n = 98) carcinoma of the uterine cervix were treated by radical radiotherapy from October 1987 to June 1992. Impact of the extent of parametrial involvement on outcome was studied. All patients were scored by the newly introduced scoring system described as follows: score 1, tumor extending <1/2 the distance to the pelvic side wall; score 2, tumor extending >1/2 the distance to the pelvic side wall but not to pelvic side wall; score 3, tumor extending to the pelvic side wall. The score in each patient was defined as the sum of the scores of both the left and right parametrial tumor extent. RESULTS: There were 53, 47, 61, 34, 25, and 24 patients in score 1, 2, 3, 4, 5, and 6, respectively. All 244 patients were subdivided into three groups described as follows: score 1 and 2, group I; score 3 and 4, group II; score 5 and 6, group III. In univariate analysis, lower score groups had better overall survival rate (OS), disease-free survival rate (DFS), local control rate (LC), and distant metastasis-free rate (DMF) than higher score groups including groups I vs. II, II vs. III, or I vs. III. The differences were all statistically significant except for the difference of the DMF in group I vs. II. In multivariate analysis, score (range 1-6) was also statistically significant in OS (p < 0.0001), DFS (p = 0.0015), LC (p = 0.0032), and DMF (p = 0.0141). CONCLUSIONS: The data suggested that the new scoring system defined by pelvic examination is a convenient, simple, and reliable method of measuring the degree of parametrial extension and predicting the outcome of patients with parametrial disease.

Adult↗
PubMed1998

The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: evidence suggestive of consequential late effect (CQLE).

PURPOSE: To correlate the acute toxicity during pelvic irradiation and the development of late rectal injury following radiation therapy for cervical carcinoma. METHODS AND MATERIALS: Two hundred and twenty patients treated with curative-intent radiation therapy between November 1987 and January 1992 were analyzed. Patients were treated initially with external beam irradiation, 40-44 Gy/20-22 fractions to whole pelvis, followed by high dose rate intracavitary brachytherapy, 7.2 Gy to point A for 3 fractions. Severity of diarrhea during radiation therapy was scored according to six criteria: fecal characteristics, frequency, onset, prescription of antidiarrheal agents, body weight loss during irradiation, and extramedical care needed. Patients were categorized as group ND (no obvious diarrhea), group MD (moderate diarrhea), and group SD (severe diarrhea) for sum score 0-1, 2-5, and > or = 6, respectively. The rate of radiation proctitis was expressed, analyzed, and compared with actuarial proctitis-free rate and prevalence. RESULTS: 1) According to the score, 76 (35%), 89 (40%), and 55 (25%) patients were categorized as group ND, group MD, and group SD, respectively. Distribution of patients and treatment characteristics among the three groups appeared similar. Patients treated with a larger field size, > or = 16.5 cm2, tended to have increased severity of diarrhea. 2) Overall, 103 patients (47%, 103 of 220) developed radiation proctitis. Twenty-one patients were in group ND (28%, 21 of 76), 43 in group MD (48%, 43 of 89), and 39 in group SD (71%, 39 of 55). 3) The five-year actuarial proctitis-free rate was 72, 52, and 29% for group ND, MD, and SD, respectively (p < 0.005). 4) Taking time evolution and recoverability into account, the effect of diarrhea on the prevalence of radiation proctitis remained statistically significant at the first through the fourth year after irradiation. 5) Severity of radiation proctitis and severity of diarrhea were not correlated (Spearman's rank correlation coefficient r(s) = 0.229, p = 0.098). 6) Cox's multivariate analysis revealed that severity of diarrhea was the only factor that significantly correlated with the development of radiation proctitis. CONCLUSION: Patients with increased acute toxicity and diarrhea during radiation therapy of cervical carcinoma significantly increased the risk of late rectal injury. This result suggested that early excessive damage of acute-responding component of rectal wall may play an important role in the initiation of late rectal injury. Radiation proctitis can be accounted, in part, as a consequential late effect.

Adult↗
PubMed1998

Bilateral pathological femoral neck fractures secondary to ectopic parathyroid adenoma.

A rare case of bilateral pathological femoral neck fractures secondary to ectopic parathyroid adenoma is reported. Both hip fractures were treated with closed reduction and internal fixation. The right hip fracture healed uneventfully, whereas the left hip fracture developed non-union that required subtrochanteric osteotomy and internal fixation and eventually healed. Neither hip developed avascular necrosis.

Adenoma↗
PubMed1998

Promotional effect of N-nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (a nitrosated Maillard reaction product) in mouse fibroblast cells.

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of model browning system generated in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass and nuclear magnetic resonance, and infrared spectroscopy in our previous study. A two-stage transformation protocol was used to chemically transform the mouse embryo fibroblasts C3H10T1/2 cells. To initiate transformation, the cells were treated with benzo[a]pyrene (BaP) (0.1 mg/ml), and NO-NTA (0.01, 0.1 and 1 mg/ml) was employed subsequently to complete the transformation process. Malignant transformed foci were formed in BaP-initiated and NO-NTA promoted C3H10T1/2 cells after 8 wk. Cells treated with NO-NTA alone failed to induce transformation. However, cells initiated with BaP and promoted by cells initiated with BaP and promoted by NO-NTA demonstrated oncogenic properties. Cell lines transformed with NO-NTA-transformed colonies exhibited enhanced growth rate, anchorage independence and tumorigenicity in animals relative to parent cells. These results indicate that NO-NTA is a new tumour promoter and may induce tumour promotion by two-stage oncogenesis. Further studies on the mechanism of action of NO-NTA are now in progress.

Animals↗
PubMed1998

The prognostic factors of lung cancer patients with brain metastases treated with radiotherapy.

PURPOSE: To analyze the prognostic factors of lung cancer with brain metastases (BM) and evaluate the role of cranial irradiation on survival. METHODS AND MATERIALS: From 1987 to 1994, 159 lung cancer patients with CT scan documented BM were reviewed. All of them underwent cranial irradiation (median radiation dose: 30 Gy). Chemotherapy and surgery of BM were performed in 21 and 10 cases, respectively. RESULTS: Overall median survival was 3.5 months and one year survival rate was 10.69%. Univariate analysis showed that the significant factors were performance status, age, total radiation dose to brain, BM as the first metastasis, neurosurgery, symptoms of urine/stool incontinence, and synchronous BM. Multivariate analysis indicated that (1) performance status (p = 0.0002), (2) total radiation dose (p = 0.0032), (3) BM as the first metastasis (p = 0.0449), (4) neurosurgery (p = 0.0233), (5) symptoms of urine/stool incontinence (p = 0.0002), and (6) the presence of a midline shift on cranial CT scans (p = 0.0063) were significant prognostic factors. CONCLUSION: The prognosis of BM in lung cancer patients is extremely poor. Radiotherapy appears as an effective means of palliation with 75% overall symptomatic response rate. Higher radiation dose (> or = 30 Gy) and neurosurgery are associated with longer survival. Good performance status, BM as the first metastasis, absence of sphincter dysfunction, and midline shift on CT scans are favorable prognostic predictors. The role of midline shift is very interesting and needs to be explored further.

Adult↗
PubMed1998

Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.

BACKGROUND: Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy. METHODS: Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 microg intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 microg neostigmine given subcutaneously (s.c.). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated. RESULTS: Intra-articular (500 microg) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 microg intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; s.c. neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 microg intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed. CONCLUSIONS: Intra-articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide-cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.

Adult↗
PubMed1998

Management of small infected tibial defects with antibiotic-impregnated autogenic cancellous bone grafting.

Between January of 1991 and December of 1993, 36 patients who had tibia fractures complicated by small infected tibia defects were treated at the authors' service. The group included 30 men and 6 women whose average age was 36.5 years (range, 18-72 years). The average follow-up period was 3.7 years. By using the Cierney-Mader staging classification of chronic osteomyelitis, 26 of 36 patients (72%) were stage 4A and 10 of 36 patients (28%) were stage 4B. Ten patients required muscle transfer. All patients were treated with a two-stage protocol. In the first stage, antibiotic-impregnated polymethylmethacrylate bead chains were used to obliterate the debrided osseous defect. In the second stage, the beads were removed, and the defects were reconstructed with antibiotic-impregnated autogenic cancellous bone graft. The time between the first and second stage was 2 to 8 weeks for patients without muscle transfer and 8 to 12 weeks for the patients with muscle transfer. The bone defects ranged from 2 to 4 cm. Wound healing and bony union were achieved in all patients. Only two patients had recurrent infections. The infection arrest rate was 94.4%. Minor pin tract infection of the external skeletal fixation was seen in two patients. Two patients developed skin rashes secondary to antibiotic therapy. Radiographs at an average follow-up of 3.7 years showed good consolidation and hypertrophy of grafted bones in all patients. After 3 to 5 years of follow-up, our results suggest that the use of impregnating antibiotics have no adverse effects on autogenic cancellous bone graft incorporation and may help to eliminate infection. This treatment protocol provided rapid recovery from osteomyelitis. The use of antibiotic-impregnated autogenic bone graft seems to be an effective and safe method for the management of small infected tibial defects.

Adolescent↗
PubMed1998

In vivo and in vitro studies on the antitumor activities of MCP (Malva crispa L. Powder).

Four short-term in vivo and in vitro tests were used to further confirm the antitumor activities of MCP, a vegetable powder, prepared from Malva crispa L. (i) In the H22 hepatoma-transplanting test, MCP had antitumor action, but MCP residue did not show such action; 5-FU appeared to have more potent antitumor activities and more harmful effects than MCP. (ii) In the micronucleus (MN) test, MCP significantly decreased MN frequency. (iii) In the cancer cell culture systems, the MCP fat-soluble extract revealed inhibitory effects on the growth and proliferation of the human hepatoma and the gastric cancer cells in a dose-response manner. (iv) In the colony formation test, MCP also altered the morphology of human gastric cancer cells. It was suggested that MCP could be consumed not only by healthy subjects for cancer prevention but also by patients with cancer as supplementary treatment in combination with anticarcinogenic drug such as 5-FU, cyclophosphamide (CP).

Animals↗
PubMed1998

Pituitary adenomas in the old-aged.

From 1986 to 1996, 187 patients with pituitary adenoma were diagnosed and received surgery at Kaohsiung Medical College Hospital. Of which, 29 patients older than 60 years were retrospectively studied. Their initial clinical symptoms, pathological findings, immunoperoxidase staining, electronic microscopic findings and hormone levels were retrospectively recorded. We found that the old patients more often suffered from the neurological deficit such as headache and visual problems rather than endocrine of the tumors cells are compared, and fewer cells and nuclei are found in the older group than that in the younger group. The secretary granules in functioning tumors especially prolactinomas in old-aged patients are larger than those in the young patients. The tumor cells in the old-aged patients have fewer subcellular organelles and secretary granules but have large secretary granules. It is concluded that: (1) transsphenoidal surgery is feasible and safe in this age group; (2) plurihormonal tumors occur more frequently in old-age than young patients; (3) clinically endocrine-inactive pituitary adenomas occur more often in old-aged; (4) pituitary adenomas in old-aged cause neurological deficit more frequently than endocrine disturbance.

Adenoma↗
PubMed1998

Successful resection of a teratoma of the third ventricle in a 3-year-old boy.

Few cases of teratoma in the third ventricle have been reported in detail. We describe a 3-year-old Chinese boy presenting with increased intracranial pressure, headache, and vomiting. Preoperative computed tomography and magnetic resonance imaging demonstrated a teratoma in the third ventricle. Complete excision of the tumor was achieved through the interhemispheric transcallosal approach. The patient did well and was without neurologic deficits postoperatively. Although the majority of tumors located in the third ventricle are malignant and can penetrate the brain tissues that constitute the wall of the third ventricle, mature teratomas are an exception and total removal may be possible.

Cerebral Ventricle Neoplasms↗
PubMed1998

Hypertrophic osteoarthropathy in nasopharyngeal carcinoma patients: two cases report.

Hypertrophic osteoarthropathy (HOA) is a rheumatic disorder characterized by digital clubbing, bone pain, and arthralgia. HOA can be idiopathic or secondary to a variety of pulmonary, cardiogenic, or malignant disorders. We present 2 male patients, aged 46 and 42, with advanced nasopharyngeal carcinoma (NPC) who developed HOA 1-4 years after radiotherapy. Differential diagnosis between HOA and coexisting bone metastasis must be made with caution. We found bone scintigraphy to be the most sensitive tool to distinguish between these 2 disease. Intense symmetrical uptake of radioisotope along the cortex of long bones, so-called parallel tract sign, is typical. Plain radiographs demonstrating prominent periosteal reaction were also effective for this. The rheumatic manifestation of HOA was paraneoplastic and related to pulmonary metastasis. The clinical manifestation of the 2 patients suggested that pulmonary metastasis should be suspected in NPC patients when HOA appears.

Adult↗