The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

KLT-based quality controlled compression of single-lead ECG

We report a rare case of orbital metastasis from hepatocellular carcinoma and review previously documented cases of this condition. The clinical, histopathological, and immunohistochemical characteristics of hepatocellular carcinoma metastatic to the orbit are described. Results from histopathological examination and histochemical findings of the orbital mass established the diagnosis. A review of 10 cases of metastatic hepatocellular carcinoma to the eye and orbit disclosed painful proptosis as the most common clinical sign of hepatocellular carcinoma metastatic to the orbit. In 5 (56%) of the 9 cases that had orbital metastasis (including the present case), the diagnosis was made after the patient first was examined with symptoms from the orbital mass. Metastatic hepatocellular carcinoma should be considered as a rare cause of painful proptosis. While patients usually are seen with signs and symptoms of widespread metastatic carcinoma, patients with hepatocellular carcinoma with orbital involvement may be first examined by the ophthalmologist because of the clinical manifestations of the disease, proptosis and pain. Other orbital lesions associated with painful proptosis are discussed briefly.     

Genotator: a workbench for sequence annotation

The clinical, pathological, and immunohistochemical features of six cases of metastatic neuroendocrine and carcinoid tumors to the thyroid simulating medullary thyroid carcinoma (MTC) are described. The patients were women between the ages of 24 and 70 years who, without symptoms or significant past medical histories, presented with either a single mass or multiple thyroid nodules. The primary source of the tumor was only discovered on follow-up. Two of the neoplasms were classical carcinoid tumors, one was a carcinoid predominantly composed of large cells, another showed a prominent oval to spindle cell component, and the two remaining cases were atypical carcinoid/high-grade neuroendocrine carcinomas. The immunohistochemical profile was inconsistent with MTC in that all tumors were negative for calcitonin and only two were focally positive for carcinoembryonic antigen (CEA). A variable pattern of staining for other neuroendocrine and epithelial markers was obtained in each case. Despite the morphologic and immunohistochemical similarities with MTC, the diagnosis of a metastatic neuroendocrine tumor to the thyroid should be favored in the presence of a predominantly interstitial pattern of spread; occurrence of multiple tumor foci; folliculotropism; rosette formations with lumen and cuticular borders; and lack of immunoreactivity for calcitonin and CEA. The differential diagnosis between MTC and metastatic neuroendocrine carcinoma to the thyroid is of importance because of the vast differences in treatment and prognosis.     

Uveal metastasis from carcinoid tumor. Clinical observations in nine cases

BACKGROUND: Carcinoid tumor is a low-grade malignancy that usually arises in the gastrointestinal tract or bronchus and rarely metastasizes to the eye. Metastasis of carcinoid tumor to the uvea can be confused clinically with other primary and metastatic uveal tumors. METHODS: The authors reviewed the records of 410 consecutive patients with uveal metastases referred to the Ocular Oncology Service at Wills Eye Hospital to identify those in whom carcinoid tumor was the primary neoplasm. The authors evaluated the clinical features of these metastases. RESULTS: Of 410 consecutive patients with uveal metastases, the primary neoplasm was a carcinoid tumor in 9 (2.2%). There were four men and five women. The mean age at ocular diagnosis was 50 years. In five patients (56%), the primary tumor was undiagnosed at ocular presentation. In the other four patients, the mean time interval from diagnosis of the primary carcinoid tumor to uveal metastasis was 89 months (range, 55-180 months). The site of the primary carcinoid tumor was the bronchus in seven patients, the esophagus in one, and the thymus in one. The site of intraocular metastasis was the choroid in six patients, the ciliary body in two, and the iris in one. All choroidal tumors had a characteristic orange color. Initial ocular treatment included external beam radiotherapy in five patients, plaque radiotherapy in two, argon laser photocoagulation in one, and local resection in one. Ocular tumor control was achieved in each patient. After a mean follow-up of 34 months, four patients (44%) are still alive. Five patients have died, with a mean survival of 34 months (range, 2-104 months) after the diagnosis of uveal metastasis. CONCLUSIONS: Uveal metastasis from carcinoid tumor is rare and tends to arise from the bronchus. Clinically, it has a distinctive orange color and may be associated with a longer systemic survival, compared with uveal metastasis from other primary sites.     

Extrarenal Wilms' tumor: diagnosis and treatment review regarding a case report

OBJECTIVES: To report a case of extrarenal Wilms' tumor, an uncommon site of presentation of this tumor type. The diagnostic and prognostic aspects of this condition are also discussed. METHODS/RESULTS: A case of retroperitoneal extrarenal Wilms' tumor in a 2-year-old child is presented. The patient underwent surgery and received postoperative chemotherapy. At 3-years' follow-up, no evidence of metastasis has been observed. CONCLUSIONS: Extrarenal Wilms' tumor is rare and has been reported in the literature principally as case reports. Its clinical presentation varies according to the extrarenal localization. The procedures utilized to determine the size of the primary tumor, regional node involvement and the presence of distant metastasis are similar to those utilized in Wilms' tumor of the kidney. Our results demonstrate the utility of chemotherapy; the cytostatic agents utilized appear to be as effective as in Wilms' tumor of the kidney. In our view, radiotherapy should be reserved for the large unresectable residual tumor mass and for distant metastasis.     

Optic nerve metastasis from a mediastinal carcinoid tumour

A 25-year-old man with a rapidly progressive metastatic carcinoid tumour arising in the mediastinum developed a metastasis to the optic nerve. This is the first instance in the literature of an ocular metastasis from this variant of carcinoid tumour. The ocular pathology, ultrastructure, and recent information on the derivation of this tumour, believed to originate in the thymus, are presented.     

Ectopic thymic carcinoid masquerading as a thyroid nodule

A 26-year old woman presented with a thyroid nodule. Ultrasound and scintigraphy confirmed the presence of a 3.5-cm non-functioning mass in the left lobe. A fine needle aspiration demonstrated unusual, malignant-appearing cells, and thyroidectomy was performed. At gross pathological sectioning, the lesion was clearly attached to, but not part of, the thyroid. Microscopic features indicated an atypical carcinoid arising in a cervical remnant of the thymus. This appears to be the first case of ectopic thymic carcinoid presenting as a thyroid nodule.     

In vitro antiphagocytic effect of Melia azedarach leaf extracts on mouse peritoneal exudate cells

The first reported case of cerebellar metastasis from primary clear cell adenocarcinoma of the fallopian tube is presented. Initially diagnosed as stage Ia, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, followed by cisplatin-based chemotherapy and whole pelvic irradiation. Thirty six months later multiple pulmonary metastases were detected that did not respond to chemotherapy. Later the patient presented with cerebellar metastasis. She received whole brain radiotherapy and steroids. The brain lesion partially responded and the patient's neurologic symptoms improved. Throughout there was no evidence of local recurrence. This case suggests that with the prolonged survival achieved by aggressive treatment occult brain metastases might become apparent.     

Assessment of self-injurious behavior maintained by access to self-restraint materials

Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1%-13% of all orbital masses (1). In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit followed by metastases from the lung, prostate and gastrointestinal tract (2). It is rare for carcinoid tumors to metastasize to the eye or to the orbit. Carcinoid tumors arise from Kulchitsky cells that originate in the neural crest. Histologically, these tumors resemble, but are not as aggressive as, adenocarcinomas. Most carcinoids arise in the gastrointestinal tract or the lung. The most common site for carcinoid metastases is the liver. On anatomical imaging studies, such as CT and magnetic resonance imaging, metastatic orbital carcinoid tumors appear as nonspecific tumor masses. Carcinoid tumors have an affinity for uptake of the radiopharmaceutical 131I-metaiodobenzylguanidine (MIBG) (3). We report a case of a patient with a known carcinoid tumor who developed a left orbital mass that demonstrated abnormal uptake of 131I-MIBG indicative of metastatic carcinoid tumor to the orbit.     

Functional activity of Rh monoclonal antibodies in ADCC assay

A 58-year-old woman with malignant mesothelioma metastatic to the orbit is reported. Malignant pleural mesothelioma was diagnosed by pleural biopsy. Marked reduction of pleural effusion was obtained with intrapleural interleukin-2 therapy. Systemic chemotherapy failed to elicit a response after the first recurrence of the tumor. Multiple systemic metastasis, including metastasis to the orbit, developed and the patient died one year and 4 months after the initial diagnosis. Although malignant mesothelioma is known to spread hematogenously, sometimes producing brain metastasis, there have been few reports of orbital metastasis, and in fact the present report may be the first clinically documented account of its kind.     

Concurrent hypercortisolism and hypermineralocorticoidism

The clinical and pathologic findings in 16 cases of carcinoid tumor of the testis are presented: 10 tumors were primary in the testis, 2 were teratomas, 2 were in the spermatic cord and 2 were metastatic. Most of these tumors occurred in middle-aged patients and the symptoms were those of testicular tumor in general, that is swelling, pain and tenderness. In none of the primary case was there evidence of carcinoid syndrome and no determination of serotonin was made before orchiectomy. Followup in 12 cases was from 4 months to 16 years postoperatively. Three patients died 2 to 4 years after orchiectomy: 1 with generalized metastasis and 2 with intercurrent diseases. Two patients were lost to followup and the remaining patients are well. Although ovarian carcinoids usually occur in teratoma and do not metastasize 1 of the primary cases produced generalized metastasis.     

Solitary breast metastasis as first manifestation of ovarian carcinoid tumor

Carcinoid tumor metastatic to the breast is very uncommon. The rarity of this finding may be the reason for its common misinterpretation as primary breast carcinoma. A patient with primary ovarian carcinoid that presented initially with a solitary breast mass is reported. A review of the literature discloses only 12 reported cases of carcinoid tumor metastatic to the breast, with none of the primaries found to be the ovary.     

The value of prognostic factors in the management of stage I nonseminomatous germ cell testicular tumors (NSGCTT)

A patient with florid hypertrophic pulmonary osteoarthropathy (HPOA) associated with metastatic nasopharyngeal carcinoma is presented. Despite the presence of metastatic disease in the thorax and in bone, the patient's main symptom was severe pain from the HPOA, which was temporarily relieved by chemotherapy. Her disease subsequently progressed during chemotherapy and the pain became resistant to conventional treatment, including high dose morphine, non-steriodal anti-inflammatory agents and steriods. It was only with local radiation to the involved joints that the pain could be controlled. Our patient demonstrates that local radiotherapy is an option for the palliation of extreme HPOA.     

Bilateral orbital metastases from breast carcinoma. A case of false pseudotumor

OBJECTIVE: To inform clinicians of a metastatic orbital neoplasm that frequently masquerades as an orbital inflammatory syndrome and to stimulate thought regarding this neoplasm's fundamental pathobiology specific to its orbital involvement. DESIGN: Interventional case report and literature review. PARTICIPANTS: A 47-year-old woman with an acquired, bilateral, diffusely infiltrative orbital process is described. INTERVENTION: The clinical and radiographic features of the patient's orbital process are reported. The review of two prior fine-needle aspiration biopsy specimens failed to reveal a diagnosis. Histopathologic examination of an open surgical biopsy specimen included standard light microscopy of frozen and formaldehyde-fixed, paraffin-embedded tissue. RESULTS: Characteristics light microscopy findings suggested the diagnosis of metastatic lobular carcinoma of the breast. The patient refused all therapeutic intervention and died 9 months after orbitotomy. CONCLUSION: The presentation of breast carcinoma metastatic to the orbit as a bilateral infiltrative process is far more common than appreciated previously. Its rate of bilateral orbital involvement is 20%, whereas this rate for other adult neoplasms is much lower. The authors report an additional case, review the clinical features of previous case reports and series, and discuss aspects of the metastatic process. Breast carcinoma must be included in the differential diagnosis of infiltrative orbital processes encountered in adult female patients. When "orbital pseudotumor" is detected in an adult female patient, a thorough medical history must be obtained and physical examination performed. If a possible primary breast carcinoma is indicated, one must be wary of metastatic disease, and a histologic orbital diagnosis is warranted. The frequency of orbital metastasis and bilateral orbital involvement of this neoplasm reinforces the possibility for organ-specific metastases.     

Bilateral candida bezoar of the upper urinary tract]

OBJECTIVE: To retrospectively analyse causes of childhood proptosis and their investigations and treatment. METHODOLOGY: The records of children under 15 years of age presenting with proptosis to The Children's Hospital, Camperdown, Sydney, were reviewed for the period 1983-93 inclusive. RESULTS: Fifty-seven cases of proptosis were found. In order of frequency the causes were; orbital cellulitis 22, thyroid eye disease 8, optic nerve +/- optic chiasm glioma 8, orbital rhabdomyosarcoma 7, metastatic neuroblastoma 4, orbital neurofibroma 3, orbital haemangioma 2, metastatic Ewing's sarcoma 2 and orbital dermoid cyst 1. Treatment depended on the cause (antibiotics, antithyroid drugs, chemotherapy, radiotherapy, surgery) and was multidisciplinary. CONCLUSIONS: The most common cause of proptosis in children presenting to The Children's Hospital, Camperdown, Sydney, was infective orbital cellulitis. The most useful initial investigation was an orbital computed tomography scan. Treatment depended on the cause of the proptosis and was multidisciplinary.     

Primitive cerebral neuroectodermal tumors excluding medulloblastomas: a retrospective study of 30 cases

We present a retrospective study of 30 cases of primitive cerebral neuroectodermal tumors (PNET), excluding medulloblastomas, referred to us postoperatively for additional therapy to evaluate prognostic factors and treatment efficiency. The histologic types were: pinealoblastomas (n = 7); ependymoblastomas (n = 2); medulloepitheliomas (n = 4), and other PNET (n = 17). The tumor was located in the supratentorial area in 24 patients and in the posterior fossa in 6 patients. Among the supratentorial tumors, 8 were metastatic. Maximal surgical resection was performed. Sixteen of 30 patients had no measurable disease after surgery and were considered as standard-risk (SR) cases, and 14 with a local residue or metastasis as high-risk (HR) cases. The objective of postsurgical treatment was to avoid radiotherapy in children below 4 years of age. It consisted of radiotherapy alone in 6 patients, chemotherapy alone in 17, and radiotherapy with chemotherapy in 7. Furthermore, high-dose chemotherapy (busulfan, thiotepa) and autologous bone marrow transplantation, performed in 6 patients, yielded a response rate of 3/6. Event-free survival (EFS) of SR patients was 37% at 3 years (95% confidence interval (CI) 14-60%) and overall survival 44% (95% CI 26-62%). Only 1 of the HR patients achieved a complete remission and all of them died early. The critical prognostic factors appear to be the completeness of initial surgical resection and absence of metastasis. These tumors have a poor prognosis. Novel strategies (high-dose chemotherapy) are needed to improve their outcome because the children concerned are very young and the effects of radiotherapy are particularly deleterious when tumors are situated in the supratentorial area.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Therapeutic possibilities of surgical treatment of patients with non-small-cell lung carcinoma and adrenal metastasis

Reports on successful surgical treatment of patients with non-small lung carcinoma and adrenal metastasis are infrequent. For this reason the Authors believe interesting to report a case of a patient with non-small lung cancer and single adrenal metastasis who underwent lung superior lobectomy and, after chemotherapy, adrenalectomy. A relapse was observed one year later in the lumbar region and the patient was reoperated undergoing removal of the recurrence associated to splenectomy and pancreas tail resection; thereafter the patient was treated with local radiotherapy. Forty-one months after the first operation the patient is well and disease free.     

Chromogranin A in cerebrospinal fluid: a biochemical marker for synaptic degeneration in Alzheimer''s disease?

OBJECTIVE: To describe the clinical, radiologic and histopathological features of two cases of carcinoma metastatic to the optic nerve with different pathways of spread. DESIGN: Chart review. SETTING: Oncology clinic in Montreal. PATIENTS: One patient previously treated for breast carcinoma and one patient previously treated for small-cell carcinoma of the lung. RESULTS: The patient with breast carcinoma was found to have an elevated mass involving her right optic nerve head. This finding was confirmed by B-scan ultrasonography. The other patient initially presented with left retinal metastasis and subsequently manifested massive secondary involvement of the ipsilateral optic nerve, documented by computed tomography. Both patients were initially treated with radiotherapy to the eye and orbit, but postmortem histopathological study showed that this treatment had little effect on the tumour. CONCLUSIONS: The histopathological observations suggest that if radiotherapy is to be used in the treatment of metastasis to the optic nerve, the dosage of radiation should be higher than that recommended for the treatment of choroidal metastasis.     

Merkel cell tumor

Merkel cell cancer is a rare carcinoma arising from the neuroendocrin cells of the skin. The diagnosis is based on the clinical behaviour, histopathologic and ultrastructural findings and immunohistochemical results. An unusual case of Merkel cell carcinoma is presented. Mass from the umbiculus and a right inguinal lymph node was excised in a 63-year-old female. The histologic features of a typical, primitive small cell tumor combined with the immunohistochemical evaluations established the diagnosis. Rare polynuclear giant cells were focally present in our case. Patient was treated with combination of chemotherapy (Cisplatin, Etoposid) and radiotherapy. Control examinations showed complete respond. One year later metastasis developed. Resection of all known metastasis were performed. Two months after the laparotomy she died of metastatic disease. The autopsy did not reveal any other primary tumor. The capricious nature of the clinical course and the differences between this tumor and other carcinomas is emphasized.