Tumors In Other Sites Research Articles

Results of RS-99 protocol for childhood solid tumors

Little was known about the therapeutic result of rhabdomyosarcomas (RMSs) and other malignant tumors until the end of the last century in China. Very few prospective clinical research results have been reported. We designed a RS-99 protocol under close cooperation of a multidisciplinary team including surgeons, radiologists, pathologists, and pediatric oncologists at Shanghai Children's Medical Center. This study aimed to improve the prognosis of childhood solid tumors and analyze the results of different tumors with the same protocol, including RMSs, the Ewing sarcoma family of tumors (ESFTs), and ex-cranial germ cell tumors (GCTs). Sixty-six patients with malignant solid tumors [RMS (n=30), GCT (n=22), and ESFT (n=14)] were enrolled on the RS-99 protocol from October 1998 to October 2006. They were 34 girls and 32 boys aged 9 to 194 months. The protocol involved surgery, radiotherapy and chemotherapy which included VCP (vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV (etoposide, vincristine and ifosfamide) for the low-risk group, AVCP (adriamycin, vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV for the intermediate-risk group and high-risk group. Peripheral blood stem cell transplantation was suggested for the high-risk group. Radiotherapy was only given for RMS and ESFT. Differences in survival between the groups were determined by comparison of entire survival curves and tested by the Kaplan-Meier method and the log-rank tests. The 5-year event-free survival (EFS) for the whole group (RMS, ESFT and GCT) was 60%. The 5-year EFS for children with RMS was 35% (95% CI 16-54), GCT was 79% (95% CI 70-88) and ESFT was 72% (95% CI 58-86). The 5-year EFS showed that the patients with RMS in the retroperitoneum-pelvis did not have a better result than those with tumors in other sites (P=0.604). The histological classification of RMS exerted prognostic influence on the estimated 5-year EFS (P=0.04). Tumor stage and risk group were also contributive to prognosis (P=0.008). For GCT patients, the primary sites of tumors and their histological classification did not influence the therapeutic result (P=0.814). The 5-year EFS was 100% in stage I and II versus 62% in stage III and IV patients (P=0.02). Because of the small number of patients, we did not analyze the prognostic factors for patients with ESFT. No organ failure or functional impairment occurred in the patients enrolled in the RS-99 protocol. One ESFT patient developed a second cancer. The RS-99 protocol is well tolerated and is reasonable for the 3 different tumors. Risk-based grouping protocol design is needed and the protocol for high risk RMS should be revised.

Lynch Syndrome—Related Endometrial Carcinomas Show a High Frequency of Nonendometrioid Types and of High FIGO Grade Endometrioid Types

Although endometrial cancer (EC) represents the second most common cancer after colonic cancer in patients with Lynch syndrome (LS), the pathologic features and behavior of LS-related EC are not well recognized. ECs from 23 patients (mean age 46.2 years) with MSH2 (16), MLH1 (6), and MLH1/MSH2 (1) constitutional mutations were evaluated for histologic type, FIGO grade, FIGO stage, association with tumors in other sites, and survival. For every LS-associated tumor, 2 same-age cases from patients with no family history of LS-associated cancer were evaluated (sporadic group). In LS-associated EC there were 13 (56.5%) endometrioid (eec) and 10 (43.5%) nonendometrioid carcinomas (neec), and among the sporadic tumors there were 44 (95.7%) eec and 2 (4.3%) neec (P = .001). The eec in women with germline LS mutation had a significantly higher FIGO grade (P = .0378) and more frequent vascular invasion than the controls. The mean survival of the entire group of 23 patients with LS-related EC was 17.326 (14.066 to 20.585). Mean survival according to FIGO stage was significant (P = .010). Difference in mean survival according to age of the patient at the time of the diagnosis (patients >46 years vs <46 years) was not significant. The mean survival of the mutated patients with eec was 20.462 (17.564 to 23.359) and was not significantly different from that of the mutated patients with neec, which was 14.240 (9.119 to 19.361). Log-rank analysis showed that histology did not affect the survival. However, the hazard ratio of neec patients, although not significant, resulted higher. Mean survival of patients with a neec tumor combined with an endometrioid component (14.375 [8.084 to 20.666]) was not different from that of patients with pure neec cancers (14.250 [7.885 to 20.615]). When compared with the control population, LS-related ECs show a wider variety of histologic types; a higher frequency of neec types despite the younger age of the patients, and a higher frequency of high grades among the eec.

Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification

Primary poorly differentiated (small round and non-small) sinonasal neoplasms comprise histogenetically and biologically diverse entities with overlapping morphologic features. Because of the limited initial biopsy tissue materials, differential diagnostic difficulties may arise and complicate timely management of some cases. We used immunohistochemical and molecular marker analyses in a large cohort of these tumors to optimize their early diagnosis and classification. Fifty-two tumors of the skull base and sinonasal regions and, for comparison, 19 poorly differentiated neoplasms of other head and neck sites were analyzed by a panel of immunohistochemical markers including those of epithelial, mesenchymal, melanocytic, and neuroectodermal origin using tissue microarray. Reverse transcriptase-polymerase chain reaction analysis of messenger RNA for EWS-FLI1 and PAX-FKHR fusion transcripts and the human achaete-scute homolog-1 gene was performed on 24 of the 52 sinonasal tumors and the 19 tumors of other sites for comparison. The immunohistochemical results substantiated the phenotypic assessment and the initial diagnosis in 49 of the 52 tumors. In 4 instances the integrated markers and phenotypic analyses led to reclassification of 3 tumors and confirmed the histogenesis of a mesenchymal tumor with aberrant cytokeratin expression. Molecular analysis of the EWS-FLI1 fusion gene transcript revealed 4 (9.3%) of the 43 tumors to be positive; all were Ewing sarcomas. The human achaete-scute homolog-1 gene transcript was identified in 10 (23.8%) of 42 tumors: 3 of 6 neuroblastomas, all 4 neuroendocrine carcinomas, and 1 each in sinonasal undifferentiated carcinoma, rhabdomyosarcoma, and melanoma. The PAX-FKHR fusion transcript was not detected in any tumors. We conclude that (1) an integrated morphologic and biomarker algorithm may better optimize the early diagnosis of poorly differentiated sinonasal and skull-base tumors; (2) molecular analysis may assist in future biological stratification of certain classes of these tumors; and (3) the human achaete-scute homolog-1 gene transcript is a nonspecific marker for the diagnosis of neuroblastoma.

Primary Mucinous Adenocarcinoma of Renal Pelvis with Carcinoembryonic Antigen Production

We report a case of primary mucinous adenocarcinoma of the renal pelvis associated with carcinoembryonic antigen (CEA) production. A 48-year-old woman was incidentally found to have an elevated serum CEA level. A series of examinations revealed a fat-containing tumor in the left kidney and excluded tumors in other sites. Radical nephrectomy was performed, and the histopathologic examination revealed a mucinous adenocarcinoma that was strongly positive for CEA. Postoperatively, her serum CEA level gradually returned to the normal range, and she had had no recurrence by 9 months postoperatively.

Renal tumours of childhood: The last 100 years and where to from here

Renal tumours of childhood represent a fascinating group of tumours in which very significant discoveries have been made in the last 100 years, leading to better understanding of these not only tumours but also tumour in general. By studying a large series of renal tumours of childhood collected through international multicentre trials, their clinico-pathological features have been better recognised resulting in more appropriate treatment and better prognosis, numerous new tumour entities have been identified, and thank to new molecular biology studies and techniques, many tumour genes and genetic abnormalities which are important in tumorigenesis have been found. The most common renal tumour of childhood is Wilms' tumour, which is now regarded as the most treatable tumour in children with overall survival of 90%. New multicentre trials are focused on reduction of treatment in order to avoid long-term sequalae of treatment, but without jeopardising these excellent survival results. Histopathological studies are searching for subtypes of Wilms' tumour, which could be treated with milder therapy, and in a recently launched trial patients will be stratified in different treatment groups on the basis of molecular features of their tumours. Molecular biology studies have helped us recognising that some renal tumours are identical to tumours of other sites (such as cellular mesoblastic nephroma and infantile fibrosarcoma of soft tissue, renal and extra-renal rhabdoid tumour), as well as that some tumours of other sites may also occur in the kidney (primitive neuroectodermal tumour, desmoplastic small round cell tumour, synovial sarcoma). Finally, some new, kidney-specific entities have been recognised too (metanephric stromal tumour, metanephric adenofibroma, anaplastic sarcoma of the kidney). It is very likely that new advances in molecular biology will result in identification of features, which are going to be even more important in predicting tumour behaviour, response to treatment and prognosis.

Surgical Treatment of Orbital Tumors at a Single Institution

The authors reviewed the experience of 19 patients with orbital tumors and summarize the clinical features, surgical treatment and outcomes. The authors searched the database for all patients who underwent surgery for the treatment of orbital tumors at a single institution between 1999 and 2007. Data from clinical notes, surgical reports, and radiological findings were obtained for the analysis. Orbital tumors constituted a heterogenous array of histopathology. The presenting symptoms were exophthalmos (52.6%), visual disturbance (26.3%) and pain (21.1%). The surgical approaches used were transcranial in 17 patients. Tumors located in the intraconal or perioptic space were surgically excised using a frontoorbital approach (8 cases), while pterional (3 cases), orbital (2 cases) and combined approaches (6 cases) were used for tumors in other sites. Total resection of tumors was achieved in 12 of 19 patients. In 4 patients with glioma and lymphoma only diagnostic biopsy was done. Three patients experienced visual deterioration postoperatively. Two patients had temporary diplopia, and one patient had temporary ptosis. Surgical treatment could be the mainstay of therapy for the majority of symptomatic orbital tumors. Many orbital tumors can be treated safely via a transcranial approach. Frontoorbital approach allows the surgeon to reach both the intraorbital and intracranial structures. Knowledge of the microanatomy of the orbit and meticulous surgical skills are necessary to overcome the pitfalls of intraorbital surgery.

Primary Gastric Choriocarcinoma

The majority of choriocarcinomas occur in the uterus as gestational malignant tumors. Rarely, a choriocarcinoma appears in the gastrointestinal tract, and the tumor is assumed to arise from a different histogenetic origin as compared to tumors of other sites. A primary gastric choriocarcinoma is a rare aggressive, widely metastatic malignant tumor, and has a poor prognosis. Reported here is a case of a 69-year-old woman with a primary gastric choriocarcinoma who presented with melena, epigastric pain, and was diagnosed with a poorly differentiated adenocarcinoma based on a preoperative endoscopic biopsy. Gastrectomy with lymph node dissection, followed by postoperative chemotherapy, is the treatment of choice. Therefore, in the case of a poorly differentiated adenocarcinoma with a bleeding tendency, a meticulous examination with the suspicion of a choriocarcinoma should be undertaken.

Pulmonary tumor types induced in Wistar rats of the so-called “19-dust study”

The incidences of primary lung tumor types histologically diagnosed in 28 groups of Wistar rats of the so-called “19-dust study” are described, the total study having been already presented by Pott and Roller (Carcinogenicity study with nineteen granular dusts in rats. Eur J Oncol, 2005; 10: 249–81). Each exposed group was repeatedly instilled intratracheally with a suspension of one type and dose of 13 non-mining dusts differing in at least one of the following properties: chemical composition, density, specific surface area, and mean particle size. Eleven of the 13 dusts were classified as respirable granular bio-durable particles without known significant specific toxicity (abbreviation of the nine-word definition: GBP). In 579 (58%) lungs of 1002 rats which survived more than 26 weeks after the first instillation of GBP, at least one primary lung tumor type was observed, and in 306 (31%) at least two types. Three benign tumor types were diagnosed in the 579 tumor-bearing rats: bronchiolo-alveolar adenoma in 46%, cystic keratinizing epithelioma in 53%, and non-keratinizing epithelioma in 2.6% of the rats. Two of three malignant tumor types (bronchiolo-alveolar carcinoma and squamous cell carcinoma) occurred in 46% and 31% of the tumor-bearing rats, respectively, and adenosquamous carcinoma was diagnosed in 0.9%. Numerous lungs with a malignant tumor also showed one or more benign tumor types. In addition, single or multiple metastases from primary tumors of other sites (mainly carcinoma of the uterus) were diagnosed in 14% of the 1002 lungs. The proportionate incidences of the four predominantly diagnosed tumor types were compared with three summarized experimental groups which were exposed either to carbon black (two size classes), to titanium dioxide (two size classes), or to the total of the other nine GBP. A significant difference was not detected. The combination of dust volume with particle size correlated best with the carcinogenic effect, in contrast to dust mass and surface area.

Biodistribution of 10B in a rat liver tumor model following intra-arterial administration of sodium borocaptate (BSH)/degradable starch microspheres (DSM) emulsion

We reported that intra-arterial administration of borocaptate sodium (BSH)/lipiodol emulsion provided selectively high 10B concentrations (approximately 200 ppm 6 h after administration) in experimental liver tumors. In the present study, we investigated the pharmacokinetics of BSH following intra-arterial administration of BSH with other embolizing agent, degradable starch microspheres (DSM). The 10B concentration in the tumor at 1 h after administration of BSH with DSM was 231 ppm. At 6 h, the 10B concentration in the tumor in BSH with DSM group was 81.5 ppm. The 10B concentration in the liver at 1 h after administration of BSH with DSM was 184 ppm. At 6 h, the 10B concentration in the liver in BSH with DSM group was 78 ppm. The tumor/liver 10B concentration ratios (T/L ratio) in the “BSH+DSM” group were significantly smaller than those in the “BSH+lipiodol” group at 1 h (1.4 vs. 3.6) and 6 h (1.1 vs. 14.9). BSH/DSM-boron neutron capture therapy (BNCT) was not suitable for treatment of multiple liver tumors due to the low T/L 10B concentration ratio. However, the high 10B accumulation in the liver tumors following intra-arterial administration of BSH/DSM emulsion suggests that BSH/DSM-BNCT has the potential for application to malignant tumors in other sites.

All in the head: obstacles for immune rejection of brain tumours.

Tumour immunology and immunotherapy is a highly active field, a clinical testing ground for cutting edge immunological techniques and concepts. But this is after many years of fundamental advances in basic immunology. In this article we suggest that immunotherapy for brain tumours cannot be rationally advanced as rapidly as that for tumours in other sites. Our understanding of anti-tumour immune responses in the brain is sketchy and frequently extrapolated from other tissues having little in common with the central nervous system (CNS). The result is that current clinical trials are built upon shakier foundations, with the somewhat naive optimism that what is looking hopeful for other tumours will also be applicable to cerebral malignancies. But of course it is easy to criticise such well-meaning attempts to treat currently incurable cancers. In the basic and preclinical domain, brain tumour models that are readily applicable to the design of future immunotherapies are only in their infancy. The ideal transplantable tumour that reiterates the key features of a malignant primary astrocytoma (poorly immunogenic, infiltrative but non-metastatic, expressing multiple mechanisms mediating immune escape) has yet to be discovered. In the meantime, we must use individual model tumours and limit the scope of the conclusions that we make from each system. Moreover, we must overcome the significant technical difficulties encountered as we strive to preserve brain integrity, whilst implanting tumours in this unique site. Or we can look to genetic models, in which there is the development of ‘spontaneous’ brain tumours (in some cases aided by the intracerebral delivery of a viral vector) incorporating many of the genetic features and heterogeneity typical of spontaneous human cancer.1 However, these models have generally been constructed to address genetic and pathological issues and they present a significant challenge for interpretable immunological studies. With these difficulties in mind, perhaps we need to accept that brain tumour models and clinical immunotherapies are currently in their first generation. To progress to a more successful second generation of therapies, there is a need to abandon the idea that an automatic one-way progression exists from rodent models to the clinic. We need better models to make better therapies, but how to choose and design the models can be greatly guided by data from clinical trials, if the trial design actually permits the generation of useful biological data. To date, most brain tumour immunotherapies have borrowed technologies and approaches already explored for tumours in other sites, principally melanoma. Thus, most of the now ‘classical’ tumour immunology approaches have been explored for brain tumour immunotherapy: cytokine immune enhancement, whole tumour cell vaccines, cytokine-modified tumour cell vaccines, gene therapies with immune bystander effects, dendritic cell therapies (reviewed in refs. 2–4). A few notable and exciting novel approaches unique to the CNS should not be passed aside, for example, exploiting the migratory properties of neural stem cells to deliver immunoactive molecules efficiently to the tumour site.5 The overall conclusions from these studies are that, depending upon the stringency of the models utilized, tumours that are pre-established in the brain are generally more difficult to eliminate than those in other sites, and may require different effector mechanisms. For example, studies in which multiple cytokines have been tested as modulators of immune responses gave different results according to the tumour model (SMA-560, B16) and site of implantation.6,7 Other attempts to create a cellular vaccine by overexpression of intercellular adhesion molecule-1 on a glioma cell line, resulted in growth inhibition of glioma cells implanted subcutaneously, but not in the CNS.8 Another recent study using a recombinant Listeria monocytogenes tumour vaccine revealed more stringent T-cell subset requirements for protection against an intracerebral challenge compared with the same tumour implanted by the subcutaneous route.9 These examples, together with the fact that no convincingly successful clinical brain tumour immunotherapy has been demonstrated to date, should force us to reassess what we understand about brain tumour immunology, rather than just brain tumour immunotherapy. It is from this perspective that we will discuss the issues pertinent to the problem by drawing from both clinical and experimental situations.

Impact of comorbidity on survival after surgical resection in patients with stage I non–small cell lung cancer

Objective: As the mean age in patients with non–small cell lung cancer increases, the proportion of patients with serious comorbidity who are considered for surgical resection also increases. Patients with non–small cell lung cancer have been shown to have a higher burden of comorbidity than do patients with tumors of other sites, such as breast, prostate, colon, and head and neck. The goal of this review was to determine the impact of comorbidity on postoperative and long-term survival after surgical resection in patients with stage I non–small cell lung cancer. Methods: A database analysis of our hospital's tumor registry included 451 patients who underwent surgical resection for pathologic stage I non–small cell lung cancer between January 1, 1994, and December 31, 1999. Comorbidity severity was prospectively determined with the Kaplan-Feinstein Index. Survival data were collected for each patient from the date of operation, with a mean duration of follow-up of 35.7 months. Bivariate statistics and Cox proportional hazards model analyses were used. Results: The mean age was 64.4 years, and 249 (55%) patients were male. The distribution of overall comorbidity severity was none, 142 (31.5%); mild, 150 (33.3%); moderate, 115 (25.5%); and severe, 44 (9.8%). The overall in-hospital mortality was 2.2% (n = 10/451). There was a nonsignificant trend toward higher hospital mortality with greater comorbidity: none, 0.7% (n = 1/142); mild, 3.3% (n = 5/150); moderate, 0.9% (n = 1/115); and severe, 6.8% (n = 3/44, P = .055). Kaplan-Meier estimated survivals at 3 years for each level of comorbidity were as follows: none, 85.6%; mild, 74.8%; moderate, 68.8%; and severe, 70.0% (P < .002). After adjustment for age, sex, T status, and tumor histologic type, the relative risks of death as a function of comorbidity were mild, 1.44 (95% confidence interval 0.89-2.34); moderate, 2.28 (95% confidence interval 1.43-3.65); and severe; 1.94 (95% confidence interval 1.023-3.70). Conclusions: Comorbidity has a significant impact on survival after surgical resection of patients with stage I non–small cell lung cancer. These data may help to explain the lower than expected survival results for patients after surgical resection for stage I non–small cell lung cancer.

34betaE12 cytokeratin immunodetection in the differential diagnosis of neuroendocrine carcinomas of the breast.

Neuroendocrine (NE) carcinomas of the breast share morphologic and immunohistochemical features with NE tumors of other sites, either resembling typical carcinoids or the highly aggressive small cell carcinoma. In addition, some mucinous carcinomas or solid/papillary carcinomas may show a major NE component. This is generally recognized by specific immunodetection of pan-endocrine markers, although this approach may fail to recognize NE tumors lacking immunoreactivity for some NE products, because the antigen is produced but not retained in the cytoplasm. It has recently been reported that high molecular weight (HMW) cytokeratin (CK), recognized by clone 34betaE12, immunostaining selectively labels non-NE carcinomas (squamous-cell and adenocarcinomas) of the aerodigestive tract and lung. The role of such CK immunodetection in the differential diagnosis of NE carcinoma of the breast was evaluated. Twenty-four cases of breast carcinomas having NE differentiation were selected. Twenty-four cases of non-NE invasive breast carcinomas served as controls. HMW CK immunoreactivity was found in all but one case of non-NE carcinomas, but in only two NE tumors (having scattered positive cells only). The authors conclude that in breast carcinomas the presence of HMW CK immunoreactivity favors the diagnosis of non-NE carcinoma, whereas its absence supports that of a NE tumor (either a carcinoid or a small cell carcinoma or a mucinous carcinoma). HMW CK can be added to the list of markers useful in the differential diagnosis of NE from non-NE tumors.

Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites.

Metastatic neuroendocrine neoplasms can have similar histologic appearances, and without an obvious primary, it may be difficult to determine the site of origin of the metastasis. Thyroid transcription factor-1 (TTF-1) is a nuclear protein expressed during the development of thyroid, lung, and forebrain. The clinical utility of TTF-1 to distinguishing between metastatic pulmonary and nonpulmonary well-differentiated neuroendocrine tumors (WDNET) has not been previously studied. One hundred fifty-eight primary and metastatic WDNET were evaluated for TTF-1 expression. The tumors included 20 pulmonary WDNET, including 17 typical and 3 atypical carcinoid tumors, 10 metastatic pulmonary WDNET, 26 intestinal WDNET, 24 metastatic intestinal WDNET, 3 thymic mediastinal WDNET, 30 thyroid tumors (10 medullary carcinomas, 5 follicular carcinomas, 5 follicular adenomas, 5 papillary carcinomas, and 5 anaplastic carcinomas), 10 parathyroid adenomas, 20 pituitary adenomas, 10 pancreatic WDNET, and 5 pheochromocytomas. TTF-1 expression was found in 19 of 20 (95%) pulmonary WDNET, 8 of 10 (80%) metastatic pulmonary WDNET, and in 0 of 50 (0%) intestinal WDNET. All thyroid tumors were diffusely positive for TTF-1, except for three anaplastic carcinomas. All parathyroid and pituitary adenomas, pancreatic and thymic WDNET, and pheochromocytomas were uniformly negative for TTF-1. These results indicate that TTF-1 is clinically useful in distinguishing metastatic pulmonary from metastatic WDNET of extrapulmonary origin.

Mixed Tumors, Myoepitheliomas, and Oncocytomas of the Soft Tissues Are Likely Members of the Same Family: A Clinicopathologic and Ultrastructural Study

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances ( epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.

Characteristics and clinical outcome of proximal-third gastric cancer

Background: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. Study Design: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. Results: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. Conclusions: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.

Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.

To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four. The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors. The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.

Minimally Invasive Cryosurgery—Technological Advances

The technological advances which have caused renewed interest in cryosurgery are the development of intraoperative ultrasound to monitor the therapeutic process and the development of new cryosurgical equipment designed to use supercooled liquid nitrogen. The thin, highly efficient probes, available in several sizes, can be placed in diseased sites via endoscopy or percutaneously in minimally invasive procedures. The manner of use is to place the probe in the desired location in the diseased tissue with ultrasound guidance. If required by the size or location of the tumor, as many as five probes can be inserted and cooled to −195°C simultaneously. The process of freezing is monitored by ultrasound which displays a hypoechoic (dark) image when the tissue if frozen. Rapid freezing, slow thawing, and repetition of the freeze/thaw cycle are standard features of technique. Clinical applications which have become common in the past 4 years include the treatment of prostatic cancer and liver tumors. The cases selected for cryosurgery are generally those for which no conventional treatment is possible. However, especially in prostatic cancer, the operative morbidity is so low and the results of therapy are sufficiently good in the short term to merit consideration of use in earlier stages of the disease. Diverse tumors in other sites, such as the brain, bronchus, bone, pancreas, kidney, and uterus, have also been treated in small numbers by cryosurgery. Judging from this experience, further expansion in the use of cryosurgical techniques seems certain.

Paediatric surgical oncology. 7—Germ cell tumours

Malignant germ cell tumours occur in children in widely differing sites in the trunk and cranium. The role of surgery in the treatment regimens has been made more definitive by advances in chemotherapy. For both the surgeon and the medical oncologist, serum tumour markers are reliable guides to the progress of disease and success of treatment. While correct surgical management alone is sufficient for a high cure rate of testicular tumours, good results for tumours in other sites are being obtained by careful planning of biopsy, chemotherapy and surgical excision.

Easy method for defining intracranial target volumes on orthogonal simulation films using magnetic resonance images.

A technique is described for simulating intracranial radiation fields. The method involves the projection of images from magnetic resonance (MR) scans to orthogonal simulation radiographs. This approach often can supplement and occasionally obviate the need for computerized tomographic (CT) assisted treatment simulation for co-planar beam arrangements in brain irradiation. Because magnetic resonance imaging can be performed in virtually any plane and is routinely carried out in sagittal and coronal planes, transferring tumor volumes to orthogonal simulation films using this technique can be done simply and accurately. The method employs an inexpensive photographic enlarger to superimpose sagittal MR scans on the lateral skull simulation films. Tumor volumes along with other structures of interest are treated onto the film and appropriate fields and blocks are contoured. The technique is performed easily in conjunction with routine simulation sessions, provided that the appropriate MR images are available. It is most suitable for planning treatment of tumors located at midline (e.g., medulloblastomas, craniopharyngiomas, brainstem gliomas, germinomas, etc.). The technique has also been used to verify the accuracy of CT-assisted treatment planning. With relatively minor modifications, eccentric tumors also can be accurately planned, and although we have restricted our description to brain tumours, the technique may be extrapolated to tumors in other sites.

Possible pathways of circulation of human endogenous retrovirus similar to mouse mammary tumor virus

It is shown that polypeptides which are immunologically related to gp52 mammary tumor virus are found in T and B peripheral blood lymphocytes in all breast cancer patients, in children with B-cell lymphosarcomas, and in B lymphocytes of some healthy donors. These proteins are not found in patients with tumors of other sites.