Multiple organ metastasis following nephrectomy for renal carcinoma]

We report a case of TNM stage II renal carcinoma with metastasis to lungs, contralateral adrenal gland and skin within 5 years following nephrectomy. The patient underwent lobectomy, adrenalectomy and cutaneous excision biopsy. The clinical course and management of metastases are discussed.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Long-term survival after bilateral adrenalectomy for metastatic lung cancer: a case report

Selected patients with solitary metastases from non-small cell lung cancer can benefit from an aggressive treatment approach that includes resection of the metastases. This approach has been used for solitary adrenal metastases, but successful long-term treatment of bilateral adrenal metastases has not been previously reported. This is the report of a patient with bilateral adrenal metastases from lung cancer who is disease-free 9 years after bilateral adrenalectomy and chemotherapy. From this evidence, one may hypothesize that adrenal metastases are occasionally lymphatic in origin and that metastases with this route of spread are more amenable to aggressive curative treatment than adrenal metastases of hematogenous origin.     

Radiology in primary hyperaldosteronism

Autonomous hypersecretion of aldosterone (primary hyperaldosteronism) is caused by either hyperplasia (usually bilateral) or an adenoma (frequently unilateral) of the adrenal cortex. Systemic hypertension due to an aldosteronoma is a potentially curable condition through surgical extirpation of the offending organ. In our experience with 37 patients clinically suspected to have primary hyperaldosteronism, radiological methods contributed significantly in preoperative diagnosis. These included (1) selective bilateral adrenal vein catheterization and blood sample collection, (2) adrenal venography, and (3) radioisotope adrenal scan. Unilateral hyperfunction could be accurately detected by the aldosterone assays from the collected samples. When adrenal venography was technically satisfactory, a nodule or aggregate of nodules measuring at least 7 mm and located on the margin of the gland or 1.5 cm or more in diameter when located in the center of the gland were readily identified. Enlarged adrenal gland on venography, in itself, was not a dependable index of a hyperfunctioning gland. Presence of a higher uptake on one side on the radioisotope adrenal scan did not always indicate the hyperfunctioning gland, but lack of lateralization of adrenal hyperfunction was more accurately predicted on the radioisotope scan than by venography. Four histopathological patterns were recognized in the surgically removed adrenal glands, but no correlation between these patterns and clinical behavior or postoperative course was found.     

Functional role of focal adhesion kinase in the process of implantation

While it is well known that unilateral tissue ischemia may result in contralateral damage in some paired organs, there is no universally accepted mechanism to explain why these contralateral changes occur. The aim of the present study was to investigate the ultrastructural and hormonal changes that occur in the contralateral nonischemic adrenal gland after unilateral ischemia of an adrenal gland in a rat model. The animals were divided into four groups of four rats each; namely, a control group which received a sham operation without any ischemic insult, a 2-h ischemic group, a 4-h ischemic group, and an 8-h ischemic group. The left adrenal blood vessels were ligated in all ischemia groups and blood samples were taken for hormonal study 2, 4, and 8 h later, after which bilateral adrenalectomy was performed to determine the ultrastructural changes. The plasma concentrations of aldosterone and cortisol were determined by radioimmunoassays. There was an increase in both aldosterone and cortisol levels related to the duration of the ischemia, but the differences among the groups were not statistically significant. Contralateral ultrastructural damage such as heterochromatin in nuclei, mitochondrial degeneration, endoplasmic reticulum cisternal widening, increased lipid droplets, and lysosomes, were demonstrated electron-microscopically after unilateral adrenal ischemia.     

Ths significance of metastases to the adrenal glands in adenocarcinoma of the colon and rectum

A study to determine the frequency of metastases to the adrenal glands following carcinoma of the colon and rectum was undertaken. Patients with, or without, adrenal spread were compared regarding age, sex, race and survival time. The over-all metastatic pattern was analyzed to determine its usefulness for predicting the presence of metastases to the adrenal glands. Autopsy reports and clinical records of patients with adrenal spread were reviewed regarding the extent of tumor involvement in the glands and possible adrenal insufficiency. Of 457 patients with adenocarcinoma of the colon and rectum who underwent autopsy, 63 or 14% had metastasis to the adrenal glands. Of these, 29 had bilateral involvement. Patients with bilateral metastases had a lower median age than did those without adrenal spread. No correlation was found between adrenal metastatic status and sex or race. Although survival time was found to be shorter for patients with bilateral metastases of the adrenal glands, adrenal insufficiency did not seem to be the reason for this shorter survival time. In retrospect, however, the presence of adrenal insufficiency could not be ruled out in several of these patients. Eight sites were studied with regard to whether or not metastatic involvement in a specific site might indicate a higher risk for simultaneous metastases to the adrenal glands. It was found for all sites that, when involved, there was a higher frequency of metastases to the adrenals than if free of tumor. Metastases especially above the diaphragm indicated a considerable risk for adrenal involvement. Different sites were combined in groups and studied in the same way. It was found that the more sites involved, the higher the relative chance of metastases to the adrenals. It was suggested that the results presented may be useful in predicting the relative chance of adrenal metastases in patients with advanced carcinoma of the colon and rectum.     

Induction of ovulation in the human with centchroman: a preliminary report

After burn or resection of one submandibular salivary gland the contralateral gland responded by an increase of proliferation. The maximal mitotic index was observed 48 hours after the resection and 72 hours after the burn. Burn of the salivary gland initiated a stable, but weak compensatory hypertrophy of the contralateral gland. Hypertrophy of the gland was accompanied by an increase in the size of the cells and the nuclei whose area enlarged by 10 and 17%, respectively. Resection of the salivary gland caused an increase in the weight of the intact contralateral gland only at the early periods of the experiment. By the 30th and the 45th day after the operation the weight of the intact contralateral gland failed to differ from control. The detected differences in the compensatory growth of the intact glands in two types of action on the contralateral salivary gland depended on the quantity of the tissue degeneration products and on the period of their stay in the organism.     

Right hemihepatectomy using a frontal approach--alternative to the conventional procedure

Right hemihepatectomy is an anatomically based major resection technique for primary and metastatic liver cancer. The most dangerous step in the procedure is to mobilize the right liver lobe from the retroperitoneum and the inferior vena cava. Large tumors or those with extension to the diaphragm, adrenal gland, or kidney may be more easily resected if a frontal approach to dividing the liver is followed. After dissection of the hilus, the liver is divided and during this step all vessels draining to the vena cava are separated. Then the right liver lobe is mobilized together with surrounding structures if necessary, but with no significant risk of bleeding. Our experience in four patients operated on for metastases or different primary tumors demonstrated that this frontal approach may be safely used and allows minimal manipulation of the tumor. Intraoperative ultrasound may be helpful in the detection of the middle and right hepatic vein.     

Colorectal manifestations of endocrine disease

PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder.     

Adrenalectomy and radical nephrectomy due to renal carcinoma

BACKGROUND: Surgery remains the only effective treatment for renal carcinoma. According the current surgical procedure, both the neoplastic kidney with its perirenal tissue and the Gerota fascia with adrenal gland must be removed. In the last years, the utility of routine adrenalectomy for kidney cancer surgery has been questioned and some authors now recommend this procedure just in selected cases. METHODS: In order to provide a contribution to this debate, 350 cases of nephrectomy after renal carcinoma have been reviewed. In all, 185 adrenalectomy have been performed and neoplastic involvement of adrenal gland has been identified just in 9 cases (4.9%), suggesting a rarity of tumor progression to adrenal gland at the time of surgery. RESULTS: Moreover, neoplastic involvement of adrenal gland has been shown in just 3 cases at preoperatively CT scan. CONCLUSIONS: The conclusion is drawn that adrenal gland may be retained in surgery for radical nephrectomy after renal carcinoma. Adrenalectomy may be recommended in doubtful cases, especially in upper pole localization and in large tumours.     

CT of abdominal wall implantation metastases after abdominal percutaneous procedures

PURPOSE: Our goal was to report the CT manifestations of abdominal wall implantation metastases occurring after abdominal percutaneous procedure. METHOD: CT scans and clinical data of six patients with abdominal wall implantation metastases at the puncture site following abdominal percutaneous procedure were reviewed. The abdominal percutaneous procedures included drainage of intraperitoneal abscess in patients with colon or gastric cancer (n = 2), transhepatic biliary drainage in a patient with hilar cholangiocarcinoma (n = 1), biopsy of intrahepatic hepatocellular carcinoma (n = 1), biopsy of a metastatic left adrenal gland (n = 1), and laparoscopic cholecystectomy in a patient with unsuspected gallbladder cancer (n = 1). RESULTS: CT enabled the diagnosis of abdominal wall implantation metastasis in all six patients and showed coexisting intraabdominal tumor sites in five patients. All abdominal wall implantation metastases were homogeneous before intravenous administration of iodinated contrast material and became moderately heterogeneous on contrast-enhanced CT scan with marked enhancement relative to adjacent tissues. CONCLUSION: Abdominal wall implantation metastases are moderately heterogeneous on contrast-enhanced CT scan with marked enhancement relative to adjacent tissues. In most cases of abdominal wall implantation metastasis following abdominal percutaneous procedure, CT shows additional intraabdominal tumor sites. This complication may occur following a variety of abdominal percutaneous procedures (either radiological or surgical).     

Ultrasonographic study of adrenal gland tumors (report of 5 cases)

The authors study the ultrasound signs of the adrenal gland based on 5 different types of operated adrenal tumours (a lipoma, an adrenal cortical adenoma, a cyst, a corticoadrenaloma, an adrenal metastasis from a renal cell carcinoma). The ultrasonographic morphological criteria of the normal adrenal gland and each type of tumour are recalled and are illustrated by clinical cases. The value of ultrasonography in the investigation of this organ was evaluated in comparison with other imaging techniques. It constitutes a good first-line diagnostic guiding examination, but needs to be completed by other investigations (computed tomography, magnetic resonance imaging, etc.). Ultrasonography can also reveal asymptomatic adrenal tumours ("adrenal incidentalomas") in which the therapeutic decision (surveillance or surgery) must be based on criteria of size and appearance after a complete laboratory and morphological assessment.     

Tuberculosis of the endocrine system

Tuberculosis now rarely affects the endocrine system. Adrenal tuberculosis is responsible for Addison's disease, but now fewer cases are affected. Although the symptoms and signs of Addison's disease appear when most of the adrenal glands have been functionally destroyed, adrenal tuberculosis results in not only chronic adrenal insufficiency but also acute adrenal failure. Dissemination of M. tuberculosis is responsible for adrenal tuberculosis, other tuberculous lesions (including the past lesions) should be evaluated. Bilateral adrenal calcification and/or enlargement which are often pointed out on abdominal CT, are important signs of adrenal tuberculosis. Thyroid gland is rarely affected, but thyroid function impairment is uncommon even if it is affected. Hypopituitarism due to intracranial tuberculoma or tuberculous meningitis are also reported. Tuberculosis of the endocrine system is a part of disseminated infection, so it should not be overlooked in miliary spread tuberculosis.     

Late metastasis in thyroid gland after nephrectomy for renal clear cell carcinoma

Renal carcinoma natural history is unpredictable. Spontaneous metastases regression after nephrectomy, as well as late recurrence are suggestive of this peculiar human neoplasm. tumor metastases localized to thyroid gland are uncommon in clinical practice; and carcinoma of the kidney, breast, lung, melanoma and gastrointestinal tract tumors are responsible for the majority of them. This paper reports on a patient with metachronous thyroid gland metastases after fourteen years of renal carcinoma nephrectomy, with one year after hemithyroidectomy recurrence on cervical striated muscle followed by surgical excision. Therapeutical aspects are briefly reviewed in literature, emphasizing surgical treatment and the need of all-life follow-up, with more alert attitude toward thyroid gland after renal cell carcinoma nephrectomy.     

Adrenal pheochromocytoma mimicking small cell carcinoma on fine needle aspiration biopsy. A case report

BACKGROUND: Fine needle aspiration biopsy (FNAB) is a sensitive and specific technique in the diagnosis of adrenal tumors. However, in rare cases the cytomorphologic features may mimic small cell neoplasms. CASE: A 54-year-old male presented with a history of hypertension and left flank pain of recent onset. Abdominal computed tomography (CT) showed a 4-cm mass involving the left adrenal gland. Fine needle aspiration biopsy (FNAB) showed groups of small round cells with hyperchromatic nuclei. The findings were highly suspicious for metastatic small cell carcinoma. Subsequently it was learned that the mass had been noted three years earlier on CT studies but had grown from 2.5 to 4 cm. A chest radiograph was unremarkable. The clinical findings were more in keeping with a primary adrenal tumor. Immunohistochemical staining done retrospectively on the cell block showed positive reactivity for chromogranin and neuron-specific enolase. These findings, correlated with the clinical features, were in keeping with a diagnosis of pheochromocytoma. Left adrenalectomy revealed a pheochromocytoma. CONCLUSION: Adrenal pheochromocytoma should be included in the differential diagnosis of small round cell neoplasms seen on FNAB of the adrenal gland. Immunohistochemistry and clinical findings are helpful in reaching the correct diagnosis.     

Consequences of prenatal morphine exposure on the hypothalamo-pituitary-adrenal axis in the newborn rat: effect of maternal adrenalectomy

The hypothalamo-pituitary-adrenal axis is already functional in rat fetuses in late gestation. We have reported previously that prenatal morphine exposure induced a severe atrophy of the adrenals and a decrease of corticosterone release in newborn rats at birth and during the early postnatal period. The first aim of the present study was to determine the effects of prenatal morphine exposure (1) on corticotrophin releasing factor (CRF) content of the hypothalamus, CRF immunofluorescence in the median eminence, CRF mRNA in the paraventricular nucleus (PVN) and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary gland; (2) on CRF-induced ACTH release from the anterior pituitary gland in vitro; and (3) on ACTH-induced corticosterone release by the adrenals in vitro. Moreover, as morphine is a hepatotoxic factor, we determined the effects of prenatal morphine on liver weight and plasma corticosteroid binding globulin (CBG) binding capacity in newborn rats. Since acute administration of morphine stimulates corticosterone secretion in adult rats and since maternal corticosterone can cross the placental barrier, we also measured both adrenal weight and glucocorticoid activity in newborns from adrenalectomized mothers treated with morphine. The present results show that prenatal morphine given to intact mothers induced adrenal atrophy and hypoactivity in newborns but did not affect the responsiveness of the anterior pituitary gland to CRF or that of the adrenal gland to ACTH. Prenatal morphine reduced both CRF content in the newborn hypothalamus and CRF immunofluorescence in the median eminence without a significant effect on CRF mRNA expression in the PVN. Moreover, morphine induced a significant decrease of POMC mRNA in the anterior pituitary gland. However, morphine did not significantly affect the weight of the liver, or the plasma CBG binding capacity for corticosterone, in rat pups. In contrast, morphine treatment of the adrenalectomized mothers did not induce adrenal atrophy in newborns and did not impair adrenal activation during the early postnatal period. Maternal adrenalectomy also prevented the effects of prenatal morphine on hypothalamic content of CRF, CRF immunofluorescence in the median eminence, and POMC mRNA in the anterior pituitary gland. However, adrenal atrophy was observed at term in newborns of adrenalectomized mothers treated with both morphine and corticosterone or only corticosterone. In conclusion, morphine given to pregnant rats induced inhibition of the hypothalamo-pituitary-adrenal axis in pups at term. As maternal adrenalectomy prevented these effects, we speculate that an adrenal factor of maternal origin, probably corticosterone, mediated these drug effects on newborns.     

Identification of a novel secretogranin II-derived peptide (SgII(187-252)) in adult and fetal human adrenal glands using antibodies raised against the human recombinant peptide

Molecular cloning of secretogranin II (SgII) in phylogenetically distant species has recently revealed the existence of a highly conserved 66-amino acid peptide flanked by preserved pairs of basic residues. This observation suggested that this peptide, named EM66, which had not been described to date, could be an important processing product of SgII. The aim of the present study was to investigate the possible occurrence of EM66 in the human adrenal gland. The EM66 peptide was generated in Escherichia coli, which was programmed to make a fusion protein containing the human EM66 sequence. The affinity-purified fusion protein was used to raise polyclonal antibodies in rabbits. The free EM66 peptide was obtained by cleavage of the fusion protein followed by high performance liquid chromatography purification. Immunohistochemical analysis using the EM66 antibodies revealed intense labeling of adrenochromaffin cells in the adult adrenal medulla and the fetal adrenal gland. A sensitive and specific RIA was developed and applied to the detection of EM66-like immunoreactivity in extracts of adult adrenal medulla and whole fetal adrenal gland after high performance liquid chromatographic analysis. A major immunoreactive species exhibiting the same retention time as recombinant EM66 was detected in both adult and fetal adrenal extracts. Taken together, these data demonstrate that posttranslational processing of SgII actually generates EM66 in the adrenal gland. The strong conservation of the amino acid sequence of EM66 in the vertebrate phylum and the occurrence of the mature peptide in both fetal and adult chromaffin cells suggest that EM66 could play an important physiological role in the human adrenal gland.     

Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas

Hemangioblastomas are low-grade, capillary rich neoplasms of the cerebellum and spinal cord that can occur sporadically or in the setting of Von Hippel-Lindau syndrome. The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase. Immunohistochemical analysis for epithelial membrane antigen (EMA) and MIB-1 was performed on paraffin-embedded sections of 27 hemangioblastomas and 5 RCC metastatic to the central nervous system. All but one hemangioblastoma demonstrated low or negative MIB-1 immunoreactivity, while 4 of 5 RCC metastases had moderate or high labeling indices. Telomerase RNA expression was assessed in 10 hemangioblastomas and in all 5 metastatic RCC by in Situ hybridization. All 10 hemangioblastomas demonstrated a lack of expression of telomerase RNA, while all 5 metastatic RCCs showed moderate to strong expression. Our results suggest that the MIB-1 labeling index is useful in differentiating hemangioblastoma from metastatic RCC and assessment of telomerase expression can also provide novel information on the difference in growth potential of these tumors.     

Axillary lymph node metastases of bronchogenic carcinoma

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.