Detection Of Occult Metastases Research Articles

Liver tumors: evaluation with contrast-enhanced ultrasound.

The development and clinical introduction of microbubble contrast agents has had a particular impact on the detection and differential diagnosis of liver tumors. The first approach widely employed made use of high-transmission power ultrasound, which destroyed the microbubbles in the process of imaging them. It is particularly successful for those agents that have a liver-specific post-vascular phase because, like liver-specific agents used in other imaging modalities such as magnetic resonance imaging and nuclear medicine, malignancies do not retain the contrast, so they stand out with very high conspicuity. Used this way with color Doppler or variants of it, more subcentimeter lesions can be demonstrated with ultrasound than with computed tomography. However, the destructive nature of this approach meant that continuous real-time scanning was impossible. Two developments allowed this to be redressed: new classes of microbubbles with perfluoro gasses instead of air and the invention of multipulse scanning modes that are sensitive to the nonlinear (harmonic) responses of the microbubbles and suppresses tissue signals. This low-power approach is now used almost exclusively, and it has the advantage of displaying the arterial phase of blood supply to a mass and a later phase when the bubbles are trapped in the sinusoids so that the vascular volume of the tissue is depicted. Malignancies typically show a low signal intensity in this phase, regardless of whether they are hyper- or hypovascular in terms of their arterial supply. This allows them to be detected with high sensitivity and much more easily than the destructive modes allowed. In addition, the arterial supply that can be now depicted in real time has characteristics that allow most benign masses to be distinguished from each other and from malignancies, thus improving specificity. Microbubbles also can be used as tracers to provide functional information that can detect occult metastases and cirrhosis noninvasively.

Jugular neck dissection for supraglottic laryngeal carcinoma with negative clinical findings in the neck (N0)

Appropriate management of patients with supraglottic laryngeal carcinoma and negative findings in the neck is still controversial. A prospective and retrospective study comprised 193 patients who were treated primary surgically between 1976 and 1993. They all had clinically and ultrasound negative findings on the neck (N0). Supraglottic carcinomas usually spread regionally. Metastases develop in the jugular group, between level II-IV. The incidence of metastases has been reported to vary from 12 to 62.5%. The size and localization of the primary tumor, its histological grade, genotype of the malignant cells, immunological and other elucidated factors can all affect the incidence of regional spread. Aim of this study was to specify the incidence of occult cervical metastases; to analyze the distribution of occult metastases related to tumor localization; to specify the distribution of occult metastases related to local spread; to analyze the distribution of occult metastases according to localization in the neck. All patients had primary surgery of primary tumor and bilateral jugular, selective neck dissection at the level II-IV with histological examination of removed lymphoid tissue. Out of 193 patients, metastatic deposits were detected in 35 (18%). Occult metastases were found in patients with carcinoma of the epilarynx in 19% (14/72) of cases, and in 17% (21/121) patients with carcinoma of the supraglottis excluding the epilarynx. This difference in frequency is not statistically significant. The incidence of occult metastases in epilaryngeal tumors did not depend on the degree of local spread. Even relatively small tumors (T1 and T2) yielded occult metastases in 33% (5/15), and 24% (6/25) of patients, respectively. In patients with T1 tumors localized at the supraglottis, excluding the epilarynx, occult metastases were not found. In the supraglottis excluding the epilarynx increased local spread was associated an increase of occult metastases. The incidence of occult metastases was directly related to the degree of the local spread of the tumor in the supraglottis excluding the epilarynx (Table 1). Occult metastases were usually ipsilateral, like the palpable ones. In medially localized tumors bilateral metastases were possible. Ipsilateral metastases were more frequent than both bilateral and contralateral ones. The possibility of contralateral and bilateral occult metastases necessitated bilateral neck dissection. Postoperative radiotherapy (60 Gy) was given to all patients with verified occult metastases. Only in two patients (1%) of the total did metastases develop subsequently, indicating the effectiveness of planned postoperative radiotherapy. Controversies in application of jugular, selective neck dissection are present since it has been in use, because of the unclear role which regional lymph tissue play in antitumor immune response. Jugular, selective neck dissection was advocated in all patients with a primary supraglottic laryngeal carcinomas. It was suggested that selective neck dissection was needed only in advanced (T3 and T4) tumors. Selective dissection is believed to be needed only when tumor has spread into the vallecula, the base of the tongue, or the medial wall of the piriform sinus. The idea of selective neck dissection has been opposed since the protective role of the cervical lymph tissue has been stressed. Ultrasound and computerized tomography of the neck cannot detect occult metastases. Today, only removal and histological examination of the lymph tissue can determine occult metastasis. The importance of selective neck dissection is considered in diagnostic biopsy procedure by which occult metastatic spread in the neck region is established. Due to the tendency of supraglottic carcinoma resulting in occult cervical metastases, early detection is imperative in order to apply the appropriate therapy. Occult cervical metastases are usually ipsilateral, but bilateral and contralateral may be found as well. Due to the aforementioned, it is necessary to perform bilateral jugular, selective cervical dissection of the neck level II-IV with histological evidence of removed lymph tissue. When metastases is verified histologically, postoperative radiotherapy is indicated as being efficient in hampering the development of palpable metastases. Five-year survival with no evidence disease is 86% (166/193).

Lunx Is a Superior Molecular Marker for Detection of Non-Small Lung Cell Cancer in Peripheral Blood

The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.

The role of radionuclide therapy in medullary thyroid cancer.

In medullary thyroid carcinoma (MTC) the detection of occult metastases is difficult and the prognosis of widespread disease is poor. In recent years several radiopharmaceuticals have become available for the diagnosis of this tumor. None of these tracers, however, has satisfactory diagnostic sensitivity and specificity. Furthermore, only few radiopharmaceutical compounds proved to have clinical value in therapeutic applications. Radionuclide therapy utilizes unsealed radioactive sources in order to deliver selective irradiation to the target organs or cancer lesions. This approach is only clinically indicated when there is a scintigraphic evidence of sufficient tumor uptake and a favorable biodistribution. When these conditions are present, radionuclide therapy can be adopted in MTC patients. Due to the low incidence of this tumor, the poor sensitivity of the available radiopharmaceuticals and their limited indications, the clinical experience in radionuclide therapy of MTC is still limited and there is general agreement among experts that it has only a palliative role. Here we briefly report the main experiences in radionuclide therapy in the past and in recent years. In addition, we summarize the results obtained with 131I-MIBG therapy at the Istituto Nazionale Tumori of Milan, as well as the most important ongoing preclinical and phase I/II trials.

Results of supraglottic partial horizontal laryngectomies

Supraglottis is a part of larynx comprising two subregions: epilarynx (suprahyoid epiglottis--including lingual and laryngeal surface, aryepiglottic folds--laryngeal surface, and arytenoids) and supraglottis without epilarynx (infrahyioid epiglottis and ventricular folds). A total of 234 patients with supraglottic squamous cell carcinoma undergoing primary surgery were analyzed in the period 1976-1996. The tumor was localized in epilarynx in 84 (25%) patients, and in supraglottis without epilarynx in 261 (75%) cases. T1 tumor was present in 145 (42%) patients, T2 tumor was found in 178 (52%) patients, while T3 was reported in 22 (6%) cases. Clinically negative neck (N0) was found in 290 (84%) patients, and palpable metastases (N1) manifested in 55 (16%) cases. Local recurrences were established in 18 (5%) patients, and subsequent postoperative cervical metastases were found in 45 (13%) cases. Five-year disease-free survival was reported in 76% (262/345) of patients. Nasogastric tubes were removed in all patients approximately 12 days following surgery. 27 patients developed laryngeal stenosis and only 2 patients were not decannulated. Voice and speech functions were satisfactory. Supraglottic laryngectomy, extended supraglottic laryngectomy is fully justified from oncological and functional aspects. Selective neck dissection in N0 cervical findings provides detection of occult metastases and indicates need for postoperative radiotherapy. Oncological and functional results of supraglottic laryngeal surgery, along with simultaneous treatment of neck by selective, modified radical neck dissection and postoperative radiotherapy offer hope for treatment of supraglottic laryngeal cancer.

Contemporary Morbidity From Lymphadenectomy For Penile Squamous Cell Carcinoma: The M.D. Anderson Cancer Center Experience

Inguinal lymphadenectomy can be curative in patients with small volume inguinal metastases and those with more significant adenopathy responding to combination chemotherapy. However, several series collected for 15 to 40 years attest to the significant morbidity associated with lymphadenectomy. We reviewed our recent experience with lymphadenectomy in patients with invasive penile cancer who were judged to require inguinal staging and therapeutic procedures to assess the incidence and magnitude of complications caused by this procedure, especially in those with no palpable adenopathy (prophylactic group). A total of 106 lymphadenectomy procedures were performed in 53 patients. The indications for dissection were prophylactic in 66 (62%) patients in whom a superficial dissection alone was completed on the ipsilateral side, therapeutic in 28 (26%) in whom superficial, deep and ipsilateral pelvic dissections were performed, and palliative in 12 (11%) undergoing extensive resection of inguinal and abdominal wall tissue after chemotherapy. Minor postoperative complications included those requiring local wound débridement in the clinic, mild to moderate leg edema, seroma formation not requiring aspiration and minimal skin edge necrosis requiring no therapy. Major complications included severe leg edema interfering with ambulation, skin flap necrosis requiring a skin graft, rehospitalization, deep venous thrombosis, death, or reexploration or other invasive procedures performed in the operating room. The incidence and magnitude of complications were compared with prior reports from our center and other series. A total of 41 (68%) minor and 19 (32%) major complications occurred with the 106 dissections (31 of 53 patients, 58%). Prophylactic and therapeutic dissections were associated with a lower incidence of complications compared with palliative dissections (p = 0.017 to 0.049). The incidence of major complications also trended lower in the prophylactic group compared with other indications (p = 0.05). One patient in the palliative group died of sepsis on postoperative day 15. When compared with 3 prior series, the incidence of skin edge necrosis in our series was significantly lower (8% versus 45% to 62%, p <0.0001). Similarly, the incidence and severity of edema in our series were significantly lower than in a prior report from our institution (23% versus 50%, p <0.0001). For select patients undergoing prophylactic inguinal dissection to detect the presence of microscopic metastases, the incidence and magnitude of complications appeared acceptable in our contemporary experience. Similarly the morbidity of therapeutic lymphadenectomy appeared acceptable, considering the potential therapeutic benefit. However, significant complications, including death, can be associated with palliative groin dissection. Optimal candidates are those having a significant response to systemic chemotherapy whose groins are grossly uninfected.

α‐catenin expression pattern and DNA image‐analysis cytometry have no additional value over primary histology in clinical stage I nonseminomatous testicular cancer

To determine whether the alpha-catenin expression pattern and DNA content have additional value over primary tumour histology, including information on vascular invasion and tunica albuginea invasion, in detecting occult metastasis in patients with clinical stage I nonseminomatous germ cell tumours of the testis (NSGCT). Fifty consecutive patients with clinical stage I NSGCT underwent retroperitoneal lymphadenectomy (RPLND) between 1986 and 1992. The orchidectomy specimens were histopathologically reviewed and immunohistochemically stained with mouse monoclonal anti-alpha-catenin antibody. The presence of an aberrant or negative staining in >10% of the malignant cells was defined as abnormal; in all other cases tumours were classified as normal. Furthermore, intact nuclei were isolated from 50 microm thick paraffin sections of the primary tumour, Feulgen stained, and analysed with an image-analysis system. Of the 50 patients, 14 had positive retroperitoneal nodes (stage IIa, 28%), one pathologically staged I patient developed a lung metastasis (stage IV) within 3 months of RPLND. Univariate analysis showed that the presence of embryonal cell carcinoma, vascular invasion and tunica albuginea invasion were predictive for occult metastases. In multivariate logistic regression analysis only vascular and tunica albuginea invasion were significant. All 11 patients with no embryonal cell carcinoma in the primary tumour were classified as having pathological stage I disease. Also, the tumours which were DNA-diploid (three) or DNA-polyploid (two) were pathologically stage I. In screening for occult metastases the DNA content and the alpha-catenin expression pattern had no additional value. Vascular and tunica albuginea invasion have prognostic value in identifying patients with clinical stage I NSGCT at high risk for occult retroperitoneal disease. In contrast, the absence of embryonal cell carcinoma could predict all patients at low risk for metastasis. The DNA-ploidy also identified patients at low risk. Other DNA-analyses and the alpha-catenin expression pattern provided no additional information. Further studies are recommended to identify patients who are at low or high risk for metastasis.

LASER THERAPY FOR CARCINOMA IN SITU OF THE PENIS

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Nov 2001LASER THERAPY FOR CARCINOMA IN SITU OF THE PENIS B.P.J. van BEZOOIJEN, S. HORENBLAS, W. MEINHARDT, and D.W.W. NEWLING B.P.J. van BEZOOIJENB.P.J. van BEZOOIJEN More articles by this author , S. HORENBLASS. HORENBLAS More articles by this author , W. MEINHARDTW. MEINHARDT More articles by this author , and D.W.W. NEWLINGD.W.W. NEWLING More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65650-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Carcinoma in situ of the penis, also referred to as Bowen’s disease or erythroplasia of Queyrat, may lead to invasive squamous cell carcinoma. We assessed the results of laser therapy for carcinoma in situ of the penis. Materials and Methods: From 1986 to 2000 we treated 19 patients with carcinoma in situ of the penis with the neodymium:YAG or carbon dioxide laser. Treatment was assessed retrospectively. No patient was lost to followup. Results: No complications developed and cosmesis was excellent. After 2 to 4 months 3 patients (16%) received repeat treatment because of incomplete disappearance of the lesion. Mean followup was 32 months. True carcinoma in situ recurrent in 5 patients (26%) at an average followup of 25 months (range 6 to 75), while 1 had infiltrating carcinoma. All patients with carcinoma in situ underwent repeat laser treatment. Conclusions: In our experience laser therapy is appropriate initial treatment for carcinoma in situ of the penis with excellent cosmetic and functional results. This therapy is also suited for recurrence without the need for more mutilating therapy. However, the high incidence of recurrence indicates the need for careful followup and patient self-examination. References 1 : Precancerous dermatoses: a study of two cases of chronic atypical epithelial proliferation. J Cutan Dis1912; 30: 241. Google Scholar 2 : Erythroplasie du gland. Bull Soc Franc Derm Syph1911; 22: 378. Google Scholar 3 : Carcinoma in situ of penis. Is distinction between erythroplasia of Queyrat and Bowen’s disease relevant?. Urology1990; 36: 479. Google Scholar 4 : Squamous cell carcinoma of the penis: premalignant lesions. Scand J Urol Nephrol2000; 205: 187. Google Scholar 5 : Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol2000; 163: 100. Link, Google Scholar 6 : Carcinoma of penis. Review of cases treated by surgery and radiation therapy 1960–1977. Urology1981; 18: 149. Google Scholar 7 : Erythroplasia of Queyrat. A clinicopathologic and histochemical study. Cancer1973; 32: 1396. Google Scholar 8 : The management and prevention of premalignant penile lesions. Scan J Urol Nephrol2000; 205: 220. Google Scholar 9 : Treatment of penile intraepithelial neoplasia (PIN) with interferon alpha-2a, CO2 laser (vaporization) and 5-fluorouracil 5% (5-FU). Eur J Gynaecol Oncol1997; 18: 410. Google Scholar 10 : Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes. J Urol1993; 149: 492. Link, Google Scholar 11 : Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser. Arch Dermatol1998; 134: 1247. Google Scholar 12 : High- and low-power CO2-lasers; comparison of results for three clinical indications. J Reprod Med1993; 38: 455. Google Scholar 13 : Laser therapy of squamous cell dysplasia and carcinoma of the penis. Urology1998; 52: 559. Crossref, Medline, Google Scholar 14 : Sapphire probe laser surgery for localized carcinoma of the penis. Eur J Surg Oncol1988; 14: 193. Google Scholar 15 : Local recurrent tumour after penis-conserving therapy. A plea for long-term follow-up. Br J Urol1993; 72: 976. Google Scholar From the Free University Medical Center and The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLont A, Gallee M, Meinhardt W, van Tinteren H and Horenblas S (2018) Penis Conserving Treatment for T1 and T2 Penile Carcinoma: Clinical Implications of a Local RecurrenceJournal of Urology, VOL. 176, NO. 2, (575-580), Online publication date: 1-Aug-2006.WINDAHL T, SKEPPNER E, ANDERSSON S and FUGL-MEYER K (2018) SEXUAL FUNCTION AND SATISFACTION IN MEN AFTER LASER TREATMENT FOR PENILE CARCINOMAJournal of Urology, VOL. 172, NO. 2, (648-651), Online publication date: 1-Aug-2004.WINDAHL T and ANDERSSON S (2018) Combined Laser Treatment for Penile Carcinoma: Results After Long-Term FollowupJournal of Urology, VOL. 169, NO. 6, (2118-2121), Online publication date: 1-Jun-2003. (2018) EDITORIAL COMMENTJournal of Urology, VOL. 168, NO. 6, (2421-2421), Online publication date: 1-Dec-2002. Volume 166Issue 5November 2001Page: 1670-1671 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordspenislaserscarcinoma in situMetricsAuthor Information B.P.J. van BEZOOIJEN More articles by this author S. HORENBLAS More articles by this author W. MEINHARDT More articles by this author D.W.W. NEWLING More articles by this author Expand All Advertisement PDF downloadLoading ...

Transxiphoid bilateral palpation in video-assisted thoracoscopic lung metastasectomy.

To evaluate indications, limits, and merits of transxiphoid bilateral palpation during video-assisted thoracoscopy (VAT) lung metastasectomy. Survey retrospective study with a minimum follow-up of 1 year. University hospital. From December 1995 to September 1999, 29 of 45 patients operated on for pulmonary metastasectomy were approached through a transxiphoid VAT. Primary sites were colon-rectum (n = 13), kidney (n = 4), limb osteosarcoma (n = 3), uterus (n = 2), larynx (n = 2), breast (n = 1), skin melanoma (n = 1), prostate gland (n = 1), back fibrosarcoma (n = 1), and ovary (n = 1). Bilateral palpation was performed in 23 patients, although only 10 had radiological evidence of bilateral disease. No perioperative or 30-days postoperative mortality was recorded. Acute and chronic pain was similar to that of other VATs and significantly less than sternotomy. Mean +/- SD chest-drain time and hospital stay were 2.8 +/- 1.19 days and 4.3 +/- 1.78 days, respectively. Sixty-nine lesions, 60 of them metastatic, were resected by laser (n = 29) or stapler (n = 40). Bilateral exploration permitted the discovery of 15 radiologically undetected lesions, 11 of which were found to be malignant. Contralateral metastases were found in 5 patients predicted to have unilateral disease. Mean +/- SD follow-up was 22.89 +/- 10.87 months (range, 9-60 months). Six patients developed new pulmonary metastases after a mean interval of 13.6 months; 3 of these patients relapsed in the unexplored hemithorax after 6, 9, and 12 months, respectively. The use of the transxiphoid VAT approach was safe, applicable in many instances, and effective in detecting occult metastases by manual bilateral palpation. The advantages of a VAT procedure can be coupled with those provided by a radical operation.

Skip metastases in colon cancer: Assessment by lymph node mapping using molecular detection

Background. Colon cancer has been assumed to spread sequentially through the regional lymphatic bed, with skip metastases occurring in only 1% to 3% of cases. Molecular techniques allow the detection of occult metastases, but to date have not been applied to assess the pattern of regional lymphatic spread of colon cancer. Methods. Fifty-five tumors from 54 patients with colonic adenocarcinoma were studied. Lymph node mapping was performed on fresh colonic specimens recording the position of each node on an anatomical diagram. Half of each lymph node was submitted for routine histology examination and half assayed for keratin 20 gene expression by reverse transcription-polymerase chain reaction. Logistic regression was used to analyze the distribution of histologic and occult metastases. Results. A total of 1084 lymph nodes were dissected (median, 19 nodes; range, 4-52). Sixty-four lymph nodes from 20 tumors had histologically evident metastases and 76 lymph nodes from 13 tumors had occult metastases. There was no difference in the distribution of either histologic or occult metastases among paracolic, intermediate, and apical node groups. Ten patients had evidence of anatomical skip lesions after lymph node mapping and molecular analysis, only 1 of which was histologically detectable. Conclusions. This study demonstrates a higher incidence of skip metastases in colon cancer assessed by molecular techniques than has previously been reported, challenging the concept of sequential development of early lymph node metastases.(Surgery 2001;129:684-91.)

Selective dissection of levels II–III with intraoperative control of the upper and middle jugular nodes: A therapeutic option for the no neck

AbstractBackgroundSelective neck dissections are accepted elective treatment in N0 patients. We present the results of a dissection of levels II to III and intraoperative pathologic control of a sample of subdigastric and supraomohyoid nodes in a group of patients with laryngeal carcinoma. When intraoperative analysis was positive, dissection of levels IV and V was completed.MethodsBetween 1991 and 1997, 145 neck dissections with intraoperative control were carried out in 79 patients with laryngeal carcinomas. Postoperative radiotherapy was used in 49 patients.ResultsThere were occult metastases in 29 neck dissections (20%). In 22 cases (15%), tumor was found in the nodes sent to intraoperative pathologic study, and dissection of levels IV and V was completed. In 7 additional cases tumor was found in the postoperative study. The sensitivity of the use of frozen sections in the detection of occult metastases was 76%. In no case were positive nodes found at level V. There was no regional relapse in any of the 145 selective neck dissections.ConclusionsThe lateral selective neck dissection is an effective method in the elective treatment of the neck of N0 laryngeal carcinoma patients. Dissection of level IV can be spared when intraoperative biopsy specimens of a sample of the subdigastric and supraomohyoid nodes are negative. According to our results, at present we do not consider it necessary to dissect level V in selective neck dissections in patients with laryngeal carcinoma. © 2001 John Wiley &amp; Sons, Inc. Head Neck 23: 441–446, 2001.

Detection of occult metastasis in patients with breast cancer.

The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary "curative" therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.

The clinical utility of multimarker RT-PCR in the detection of occult metastasis in patients with melanoma.

Cutaneous melanoma is characterized by a high propensity for metastasis. Currently, surgical intervention remains the mainstay of therapy. This approach has proven most beneficial when the diagnosis is of early stage primary lesions. Likewise, patients undergoing resection for a solitary site of metastasis have shown a survival advantage. Identification of metastatic disease depends predominantly on radiographic techniques requiring the presence of significant tumor burdens for successful imaging. However, at that time, the role of surgery and/or biochemotherapy may be of limited value. Techniques to identify minimal disease states may permit more accurate assessment of prognosis. The detection of occult tumor cells by RT-PCR in the blood, lymph nodes, and bone marrow of melanoma patients provides one such approach to monitor tumor progression. Single-marker RT-PCR has been used as one such approach but is noted to have limitations in sensitivity and specificity based on the heterogeneity of tumor marker expression among tumors as well as within an individual tumor lesion or among multiple lesions in individual patients. We employed a multimarker reverse transcriptase polymerase chain reaction assay that demonstrates improved sensitivity over a single-marker approach. Currently, the consequences of detecting systemic subclinical metastasis remain unknown pending longer-term follow-up. The detection of occult melanoma cells using molecular techniques in conjunction with known clinicopathologic prognostic factors may provided a novel and efficient approach in monitoring tumor progression and further identify high-risk patients diagnosed early in the disease course.

Pathologic Detection of Occult Metastases in Regional Lymph Nodes in Patients with Head and Neck Cancer

Squamous carcinomas of the head and neck region are exceedingly common problems in the routine practice of head and neck tumour surgery. Well-defined treatment protocols have evolved to manage patients afflicted with such tumours. This article explores the role of the hospital pathologist in the detection of occult metastases. The conventional approach to evaluation of cervical nodes from a neck dissection is reviewed, and then the potential utility of more recently developed diagnostic approaches (such as immunohistochemistry and polymerase chain reaction) is explored.

Immunohistochemical detection of occult metastases in paraaortic lymph nodes in advanced gastric cancer.

Some Japanese surgeons have examined the utility of super-extended paraaortic lymphadenectomy (PAL) as part of the surgical treatment for advanced gastric cancer. However, therapeutic value of this PAL remains controvertial. The purpose of this study was to evaluate appropriate candidates who might benefit from PAL by the immunostaining with cytokeratin (CK) of the macroscopically intact paraaortic nodes. A total of 525 paraaortic nodes from 35 patients was serially sectioned and stained with hematoxylin-eosin (H&E) and CK staining. A total of 17 nodes (3.2%) from 7 patients (20.0%), among 525 macroscopically intact paraaortic nodes, was determined to be immunopositive for CK. In 4 patients, 8 H&E-positive nodes with metastases were all immunopositive and, in addition, 4 H&E-negative nodes were also immunopositive. Furthermore, 3 patients with H&E-negative nodes had five immunopositive nodes. Immunostaining with CK was useful for detection of occult metastases. Survival was prolonged in 3 of these 7 patients. The incidence of CK-positive nodes was significantly higher in patients with gross type of 3 or 4 gastric cancer and in patients with H&E-detected nodal metastasis within group 3 (N3) nodes. It seems that such patients would benefit from prophylactic PAL.

Detection of occult metastases in lung carcinomas: progress and implications for lung cancer staging.

The ability to detect occult regional and systemic metastases in patients with operable lung carcinoma could have a significant impact on the management of the disease. Here, we review the literature, including studies from our own laboratory, regarding the clinical significance of the presence of occult metastases in patients with lung cancer. The accumulated evidence strongly suggests that the detection of occult regional and systemic metastases is an important predictor of disease progression. The use of this method should be considered in the future design of lung cancer clinical trials, at the very least. The detection of occult metastases should have an impact on lung cancer management; to reflect this, we propose a change in the TNM staging system to indicate the presence or absence of occult regional (lymph node) and systemic (bone marrow) metastases. The proposed change is TNnMm, where n and m are occult nodal and bone marrow metastases status.

La scintigraphie par 18f-fluorodésoxyglucose (fdg) dans les cancers mammaires

Fluorine 18-fluorodecxyglucose is concentrated in malignant cells and can be detected with positror, emission tomography (PET). In breast disease, this non invasive method seems to be useful in cases where the initial staging (clinical examination, mammagraphy, fine needle aspiration of palpable mass) is insufficient. A large number of published studies have demonstrated that PET scan is better than conventional imaging in the initial staging (primary tumour, lymph node involvement, distant metastases), in the evaluation of fatty and dense mammary gland or mastopathy, in the detection of recurrence in previously treated breast cancer (surgery, radiation therapy, brachytherapy, mammaplasty) and in the detection of occult metastases suspected on a raising tumour marker. PET scan performances must be confirmed and would become a useful diagnostic test in breast cancer as well as a necessary tool in the assessment of the therapeutic efficacy.

Molecular Staging in Melanoma Improves Prediction of Outcomes

Even when patients have negative lymph nodes after surgery for malignancies, metastases frequently occur later. This Florida study assessed the ability of a new, highly sensitive molecular assay to detect occult metastases in 114 patients with early-stage …

Role of suprahyoid neck dissection in the treatment of squamous cell carcinoma of the lower lip.

Treatment of squamous cell carcinoma of the lip is primarily surgical. Unlike other oral lesions, lower lip cancers do not metastasize to lower cervical lymph nodes without invading submental and submandibular lymph nodes. This study presents 30 patients with N0 lower lip carcinoma who were treated by en bloc resection of the tumor with suprahyoid neck dissection. Occult metastasis was found in 4 patients (13%). Four patients, 3 of whom had no occult metastases, died of local or regional uncontrollable disease. Suprahyoid or modified radical neck dissection appears to be beneficial, even in small tumors of the lower lip, in detecting occult metastases.

Detection of regional lymph node metastases in colon cancer by using RT-PCR for matrix metalloproteinase 7, matrilysin.

Lymph node metastasis is the most important prognostic factor in colon cancer. However, more accurate screening for metastasis than that afforded by conventional pathology remains elusive. We have employed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for a matrix metalloproteinase (MMP), 'matrilysin', because this gene is epithelial-specific and consistently expressed in colorectal cancer cells. The sensitivity of this assay was examined with the matrilysin-producing rectal cancer cell line 'CaR-1'. Matrilysin mRNA was detected in this system when more than 10(4) matrilysin-positive cells existed in a lymph node of ordinary size. Fourteen of 15 (93%) primary colon cancers and none of the surrounding normal tissues expressed matrilysin. All 10 histologically-positive lymph nodes were positive for matrilysin, while of 60 histologically-negative lymph nodes, eight were positive for matrilysin. When the additional sequential sectioning and histological re-examination was performed on five of these eight 'matrilysin-positive, but histologically-negative' lymph nodes, micrometastases were detected in three. Only one of the lymph nodes that were histologically-positive, but negative by matrilysin assay was from a patient with colon cancer in which matrilysin was not detected. In conclusion, RT-PCR assay for matrilysin is a sensitive method for detecting occult metastases in patients with colon cancer, and may complement histologic examination.