Molecular biologic markers and cancer risk assessment

BACKGROUND: Malignant melanoma is the second most common vulvar malignancy. The superficial inguinal lymph nodes are the main site of metastases. Endometrial metastasis of vulvar malignant melanoma has not been previously reported. CASE: Vulvar malignant melanoma was diagnosed in a 60-year-old, postmenopausal woman. Immunohistochemical stains were positive for vimentin and S-100 protein and negative for HMB-45. Six months following vulvectomy, right inguinal lymphadenectomy and immunotherapy, curettage was performed due to postmenopausal bleeding. Histologic and immunohistochemical examinations revealed metastatic malignant melanoma with the same staining reactivity as the primary vulvar neoplasm had. Hysterectomy and bilateral salpingo-oophorectomy was performed, disclosing invasion of the endometrium and the inner two thirds of the myometrium. CONCLUSION: Only 10 other cases of endometrial metastases from malignant melanoma have been previously reported. All those cases involved a primary tumor occurring in the trunk and extremities. This is presumably the first report on endometrial and myometrial metastases from vulvar malignant melanoma.     

Metastatic melanoma of unknown primary origin shows prognostic similarities to regional metastatic melanoma: recommendations for initial staging examinations

BACKGROUND: Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The prognostic significance of this diagnosis is still controversial. METHODS: Of 3258 patients with malignant melanoma recorded during the period 1976-1996, 2.3% had metastases of unknown primary origin. Anatomic distribution, clinical stage, and survival probabilities were evaluated. RESULTS: Thirty patients were classified as having cutaneous or subcutaneous in-transit metastases, and they showed a 5-year survival rate of 83%. Thirty-seven patients were classified as having lymph node metastasis, and their 5-year survival rate was 50%. Disseminated disease was diagnosed in only 8 patients, who had a median survival of 6 months. Comparison of survival probabilities for patients with in-transit metastases and unknown primary tumors with the probabilities for those with cutaneous primary tumors revealed a significant advantage for the former group. No significant differences were found for patients with lymph node metastasis when those with unknown primary tumors were compared with those who had cutaneous melanomas with regional lymph node metastasis. CONCLUSIONS: The clinical disease course of patients with metastatic melanoma of unknown primary origin is similar to that of patients with primary cutaneous melanoma when the same clinical stages of the disease are compared. Based on the assumption that the majority of regional metastases develop from completely regressed primary cutaneous melanoma, recommendations for initial staging examinations in patients with unknown primary tumors are given in this article.     

Bronchioloalveolar carcinoma of the lung

Iodine-123-iodobenzamide (IBZM) is a specific antagonist of dopamine D2 receptors and usually is used to study neuropsychiatric disorders. It also has a substantial affinity for malignant melanomas. This has been attributed to specific dopamine D2 receptor binding on melanoma cells because melanocytes and dopaminergic neurons share the same ectodermal origin and are both able to produce melanin. However, IBZM binding to melanoma metastases occurs predominantly 24 hr after injection, which is much later than maximal specific D2 receptor binding is expected. Furthermore, IBZM binding is not consistent in melanoma patients. This points to another mechanism of IBZM binding to melanoma cells. The aim of this study was to characterize IBZM-binding metastatic melanoma patients clinically and histologically to shed light on the nature of this mechanism. METHODS: Twenty-one patients with proven or suspected metastases of a malignant melanoma entered this prospective study after surgical removal of the primary tumor. Whole-body scans, planar scintigrams and SPECT scans were performed 2-5 hr and 1 day after intravenous injection of 185 MBq IBZM. RESULTS: The suspected diagnosis of metastatic cancer was later confirmed in 17 patients by histology, clinical follow-up, x-ray, CT or other radiologic methods. Four patients were free of tumor tissue at the time of investigation and remained stable for 2 yr thereafter. Twelve of the 17 patients had a melanotic and 5 had an amelanotic subtype of the tumor. Iodine-123-IBZM accumulation occurred in the metastases of 10 of the 12 patients with melanotic melanoma and in 0 of the 5 patients with the amelanotic tumor type (p < 0.01; chi-square test). Furthermore, IBZM accumulation occurred in 0 of the 11 amelanotic metastases but in 20 of the 25 melanotic metastases (p < 0.001). The sensitivity is, thus, 83% for the detection of melanotic melanoma metastases on a patient basis and 80% on a lesion basis. Iodine-123-IBZM scintigraphy demonstrated one previously unknown metastasis. Six initially suspected lesions were not due to melanoma metastases and were IBZM-negative. No false-positive IBZM accumulations occurred in our patients. CONCLUSION: Iodine-123-IBZM binds to melanotic malignant melanomas with high specificity and moderate sensitivity but not to amelanotic melanomas. Our data suggest that the tracer does not bind to membrane dopamine receptors of the tumor but is built in or closely bound to intracellular melanin.     

Elective lymph node dissection in malignant melanoma--status of color Doppler findings

Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 < 1 mm tumor thickness). In comparison with a historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).     

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.     

Failed or difficult laparoscopic cholecystectomy: can preoperative ultrasonography identify potential problems?

A prospective study was performed to assess the role of preoperative ultrasonography in predicting failed or difficult laparoscopic cholecystectomy. Fifty patients underwent detailed preoperative ultrasound examinations. The number and size of calculi, evidence of acute or chronic cholecystitis, gallbladder morphology, and the presence or absence of aberrant anatomy were documented. A comparison was made of the surgical outcome and the ultrasound findings in each patient. Six patients were converted to open cholecystectomy because of inflammatory changes in the gallbladder. The preoperative ultrasound studies in 5 of these patients demonstrated evidence of cholecystitis and cholelithiasis. Gallbladder wall thickening and contraction were also seen. Five gallbladder resections had intraoperative difficulties; preoperative ultrasonography demonstrated a thickened gallbladder wall in 2. Of 31 uneventful cases, 7 had evidence of gallbladder wall thickening and/or contraction. There were no ultrasound features that identified between the unsuccessful, difficult, or uneventful laparoscopic cholecystectomies. We conclude that detailed preoperative ultrasound evaluation of the gallbladder in patients destined for laparoscopic cholecystectomy is of little value in screening for difficult or unsuitable cases.     

Mutations in purine nucleoside phosphorylase deficiency

PURPOSE: The aim of this study was to investigate the incidence of unexpected malignant uveal melanoma in the age of ultrasound diagnostics and to highlight the reasons for misdiagnosis. PATIENTS AND METHODS: All eyes were surgically removed and histologic examination was performed between 1981 and 1995. The eyes were investigated for the incidence of uveal melanoma, and the history of the unexpected malignant melanoma of the uvea or ciliary body highlighted. RESULTS: 225 (18.7%) eyes with malignant melanoma out of 2583 enucleated eyes were found. Eight (3.6%) of 225 were clinically unexpected. The clinical misdiagnoses were secondary angle closure or open angle glaucoma (6), retinal detachment (5), iritis (1), scleritis (1), cataract (4) and an intraocular mass that was believed to be a metastasis of a colon carcinoma. Seven of eight eyes were blind, and one eye had light perception only. The longest follow up before enucleation was 13 years. On three eyes diagnostic ultrasound was reportedly performed without specific diagnosis of uveal melanoma. Surgery was performed on four eyes for reasons of uncontrollable intraocular pressure or retinal detachment up to five years before enucleation. Histologic diagnoses were 3 epitheloid-type, 2 spindel-type and 3 necrotic melanoma of the uvea. Four eyes showed scleral invasion by tumor cells and one eye an invasion into the episcleral space. CONCLUSIONS: Even today the rate of unexpected uveal melanoma, according to our study is 3.6%. Therefore, all blind eyes without visualisation of the posterior pole should be examined with ultrasound in order to diagnose an uveal melanoma prior to enucleation.     

Radical resection of primary malignant melanoma of the gallbladder with multiple metastases: report of a case

We present herein an usual case of primary malignant melanoma of the gallbladder in a 51-year-old man in whom an exploratory laparotomy for melena revealed six malignant melanoma lesions located in the gallbladder, main pancreatic duct, stomach, duodenum, jejunum, and a mesenteric lymph node. Total pancreatectomy was performed and histologically, junctional activity was seen only in the gallbladder, suggesting that this was the primary site. No melanotic lesions were found on the skin or eyes. The metastases to the main pancreatic duct and gastrointestinal tract appeared likely to have occurred as a consequence of the mucosal dissemination of the tumor cells shed into the bile. The post-operative course was uneventful and combined chemotherapy was administered for 16 months. No new metastatic lesions were found until 21 months postoperatively, when metastases were detected in the brain and thoracic spinal cord. These metastatic tumors were removed surgically, but the patient died from cerebral disturbance 26 months after the initial operation. Thus, we consider that aggressive surgical therapy was effective for extending the survival time and improving the quality of life of this patient.     

Planar coincidence scintigraphy and PET in staging malignant melanoma

This study describes a comparison of simulated planar positron coincidence scintigraphy (PCS) with PET in the whole-body staging of patients with malignant melanoma using 2-18F-fluoro-2-deoxy-D-glucose (FDG). METHODS: In 55 patients with either known metastatic or newly diagnosed malignant melanoma, whole-body PET scanning was performed on a conventional full-ring dedicated PET tomograph, and multiaxial sections were obtained. Furthermore, anteroposterior projection images simulating images of a dual-head Anger camera operating in coincidence mode were obtained from the PET raw data. Each study was evaluated separately and blindly. Imaging findings were confirmed by biopsy or by at least one imaging modality in addition to PET. RESULTS: A total of 108 lesions were evaluated, of which 76 proved to be melanoma metastases. Whole-body PET correctly demonstrated 68 metastases, 6 lesions were classified as questionable metastases and 2 were missed. Whole-body PCS correctly demonstrated 14 metastases, 22 lesions were classified as questionable metastases and 40 metastases were missed. The sensitivities of whole-body PET and whole-body PCS were 89% and 18%, respectively. In PCS lesions in regions of high background activity, such as in the abdomen, were missed more often than in PET (p < 0.05). The tumor-to-background contrast was generally lower in PCS than in PET. A further decrease in PCS detection was found in lesions of < 22 mm in diameter. CONCLUSION: The lack of sensitivity precludes the clinical use of whole-body PCS in staging malignant melanoma.     

Intraoperative determinants of unresectability for patients with colorectal hepatic metastases

BACKGROUND: Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. METHODS: This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. RESULTS: Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. CONCLUSIONS: A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease.     

Imaging of abdominal manifestations of melanoma

Despite an increasing incidence of melanoma in this country, innovative new therapies are allowing patients to receive aggressive experimental treatments. Diagnostic imaging remains crucial for tumor staging and for follow-up of patients being treated with these protocols. Because metastases occur in the abdomen and pelvis in approximately 60% of patients, it is important to accurately identify all sites of tumor spread. A variety of imaging techniques are used to image these patients, with CT currently being used for staging purposes and to guide diagnostic biopsies. Other imaging techniques, such as MR, ultrasound, and fluoroscopy, are currently reserved for investigating specific complications of melanoma, such as vascular invasion, hemorrhage from a tumor, and small bowel involvement, including intussusception. Recently, whole body positron emission tomography (PET) imaging using 2-deoxy-2-fluoro-D-glucose (FDG) has been shown to be highly accurate in assessing patients with metastatic malignant melanoma. This review illustrates the spectrum of manifestations of metastatic melanoma throughout the abdomen and pelvis, including solid organ, hollow lumen, and retroperitoneal involvement, and demonstrates some of the typical and atypical manifestations that may be identified.     

Lymphographic evaluation of 250 patients with malignant melanoma

Foot lymphography was performed in a selected group of 250 patients with malignant melanoma, with different sites of origin and of various stages. The overall incidence of metastases was 40%. The case material was evaluated in detail; the tumors of the inferior limb and those on different sites, e.g., vulva and abdomen, were considered separately. In the group of 188 patients with melanoma of the inferior limb, the incidence of metastases was 42%. In 51%, histologic confirmation was obtained. In the group of 62 patients with melanoma of different sites of the body, the incidence of metastases was 34% and histologic confirmation was obtained in 21 patients. The values of accuracy, sensitivity, and specificity based on the histologic confirmation of the lymphographic reports ranged from 88% to 96%. These data justify the use of lymphography in the initial diagnostic work-up and in the follow-up of these patients.     

Salt-sensitive hypertension induced by sensory denervation: introduction of a new model

OBJECTIVE: To determine whether surgeons and residents with minimal training can evaluate accurately emergency ultrasound (US) examinations compared with radiologists for blunt abdominal trauma. METHODS: Over 7 months, we conducted a prospective study comparing the evaluation of emergency US for blunt abdominal trauma by surgeons and attending radiologists. US readings from the surgical team and the radiologists were correlated with outcome. RESULTS: One hundred-twelve patients were included in the study. Ninety-two patients had an US read as negative by the surgical and radiology services with no subsequent injuries identified. Eighteen patients had an US deemed positive by the surgical service and radiologists. Injuries were confirmed in this group by operation or computed tomography. One patient had an US deemed positive by the surgical team and subsequently negative by the radiologist. A diagnostic peritoneal lavage was performed which was negative. Another patient had an US interpreted as negative by the surgical evaluator and positive by the radiologist. Exploratory laparotomy was negative for intraabdominal hemorrhage or organ injury. Overall results reveal an accuracy on US reading of 99% for the surgical team and 99% for the attending radiologists. CONCLUSION: Surgeons and surgical residents at different levels of training can accurately interpret emergency ultrasound examinations for blunt trauma from the real-time images, at a level comparable to attending radiologists.     

Constructing international professional identity: what psychiatric nurses talk about on the Internet

BACKGROUND: S100 proteins are low-molecular-weight calcium-binding proteins and appear to play an important role in various cellular processes such as cell division and differentiation. In histopathology, S100 is widely accepted as the marker of choice for immunohistochemical identification of malignant melanoma. When S100 was detected in the serum of patients with malignant melanoma, it was suggested that serum S100 may be a useful marker for the stage of disease. OBJECTIVE: The aim of this study was to examine serum S100 concentrations of patients with different stages of malignant melanoma and to determine the value of serum S100 in the follow-up of melanoma patients during treatment. METHODS: Sera were obtained from 73 melanoma patients in different stages of the disease. The control group consisted of 130 healthy subjects. In 4 patients with metastatic melanoma, serum S100 was measured serially. Serum levels were measured by a commercially available immunoradiometric assay. RESULTS: While only 1 out of 25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage III, 21.4%) showed detectable serum S100 levels, 27 of 34 patients with disseminated disease (stage IV, 79.4%) had elevated serum S100. Interestingly, rising levels of serum S100 in the serial measurement indicated progression of the disease, and a complete decline reflected 2 patient remissions. CONCLUSION: The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.     

Evaluation of plain abdominal radiographs in the diagnosis of abdominal pain

In an effort to develop referral criteria for the ordering of abdominal radiographs for patients presenting with abdominal symptoms, we prospectively studied the relation between clinical data and radiographic abnormalities. Of 1780 examinations, 179 (10.0%) showed some radiographic abnormality. If abdominal radiographs would have been limited to those patients who had moderate or severe abdominal tenderness, or to patients with a high clinical suspicion of bowel obstruction, renal or ureteral calculi, trauma, ischemia, or gallbladder disease, regardless of the degree of tenderness, 956 (53.7%) examinations would not have been done. All radiographic abnormalities reflecting a serious pathologic process would have been identified. Only 33 (3.5%) abnormalities of limited significance, almost all localized or generalized ileus, would have been undetected. The adoption of these referral criteria would result in minimal loss of clinically useful information, large financial savings, and a reduction in radiation exposure.     

Secondary varicocele as a clinical manifestation of primitive retroperitoneal tumor

Cutaneous and subcutaneous masses of the abdominal wall are uncommon. However, a variety of benign and neoplastic entities can be encountered in this region. We report a series of 22 fine-needle aspirations (FNA) of malignant cutaneous and subcutaneous lesions involving the abdominal wall. All of these lesions were metastatic neoplasms. There were 14 females and eight males, with an age range of 35-83 years (mean 65 years). Twenty-one had a previous history of malignancy. The mean interval between the primary diagnosis and FNA was 26 months (range 1.5-128 months). The sites of origin in order of decreasing frequency were colon (n = 4), ovary (n = 4), breast (n = 3), endometrium (n = 2), melanoma (n = 2), and one case each of cervix, urinary bladder, kidney, pancreas, gallbladder, and lymphoma. One case was a squamous-cell carcinoma of unknown origin. Fourteen of the 22 patients were dead at the end of this study, with a mean survival of 8.4 months (range 0.5-44 months) following FNA. One patient was alive with disease at 13 months, and seven patients were lost to follow-up. Based on this data and on review of the literature we conclude that the majority of malignant cutaneous and subcutaneous lesions of the abdominal wall subject to FNA biopsy are metastatic tumors which originate from intra-abdominal, pelvic, and retroperitoneal organs and that FNA is a highly useful technique in the assessment of these lesions of the abdominal wall.     

Gallbladder ejection fraction. Nondiagnostic for sphincter of Oddi dysfunction in patients with intact gallbladders

Thirty consecutive patients with intact gallbladders and biliary pain were evaluated to determine whether gallbladder ejection fraction could identify sphincter of Oddi dysfunction. The mean gallbladder ejection fraction was 45% in patients with abdominal pain and 72% in normal controls. Gallbladder ejection fractions were then correlated with endoscopically measured sphincter of Oddi pressures in patients with abdominal pain. The mean gallbladder ejection fraction was 41% in 7 patients with elevated sphincter pressures and 46% in 23 patients with normal pressures (P = NS). Thirty-six percent of patients with elevated pressures and 33% of patients with normal pressures had abnormal gallbladder ejection fractions. Gallbladder ejection fraction had a sensitivity of 33%, a specificity of 63%, and a positive predictive value of 25% for detection of elevated pressures. Regression analysis revealed a poor correlation between sphincter pressure and gallbladder ejection fraction (r2 = 0.02). These findings suggest that gallbladder ejection fraction cannot be used to diagnose sphincter of Oddi dysfunction in patients before they undergo cholecystectomy.     

Treatment of lung metastases from malignant melanoma with IL-2 inhalation therapy

Seven patients with pulmonary metastases of malignant melanoma were treated with inhalation therapy with 36 million IU interleukin-2 for six months. Inhalation therapy was combined with four bolus infusions of DTIC at a dose of 850 mg/m2 once every four weeks. Response rates were 71.4% with 2 patients achieving a complete remission (CR), 2 partial remissions (PR), 1 stable disease (SD), and 2 progressing disease (PD). Therapy was well tolerated with low toxicity. Six of the patients developed cough; one patient was slightly feverish. We conclude that inhalation therapy of lung metastases is a promising addition to the therapeutic arsenal against malignant melanoma.     

Lymph node sonography versus palpation for detecting recurrent disease in patients with malignant melanoma

The aim of this study was to examine the efficacy of lymph node palpation versus high resolution lymph node sonography for the detection of lymph node metastases in patients with malignant melanoma. We retrospectively evaluated 2256 pairwise lymph node examinations of the cervical, axillary and inguinal region by palpation and sonography in 264 patients with resected melanomas greater than 0.75 mm of invasion thickness. Lymph node metastases occurred in 50 patients (19%) which were detected in 38 (76%) by both methods in agreement. In 7 cases (14%) palpation failed, in 3 cases (6%) sonography failed and in 2 cases both methods failed to identify metastases. The overall sensitivity of detecting metastatic disease was 82% for palpation and 90% for sonography which was statistically not different. The overall specificity by sonography (99%) was significantly better than for lymph node palpation (88%). Taking into account the results of this analysis, we conclude that patients with a negative result by lymph node palpation do not need further sonography for verification. However, any suspect result by palpation should be additionally evaluated by lymph node sonography in order to rule in or out metastatic disease.