The importance of surgical margins in retroperitoneal sarcoma.

Surgery is the "gold-standard" treatment for retroperitoneal sarcomas, but local recurrence is common, and can cause disease-related death. Complete gross resection is associated with improved survival, but debate exists as to whether resection of adjacent organs to improve margins or prescription of neoadjuvant radiation leads to better outcomes. This review summarizes data addressing prognostic value of margin, extent of surgery necessary to optimize treatment of retroperitoneal sarcomas, and role of histology in optimizing therapy.

Schawannoma retroperitoneal interaorto-cava. A propósito de un caso / Retroperitoneal schwannoma betwen the aorta and vena cava. A case report

No disponible

Case of concurrent benign metastasizing leiomyoma in the lung and retroperitoneum, with a focus on its etiology.

We report a rare, simultaneous occurrence of benign metastasizing leiomyoma in the lung and retroperitoneum in a 49-year-old woman who had previously undergone myomectomy at 35 years of age and hysterectomy at 45 years of age for multiple recurrences of histologically benign uterine leiomyomas. At 49 years of age, computed tomography-guided biopsy indicated benign metastasizing leiomyomas in the lung. In addition, a retroperitoneal leiomyoma was found that was resected along with both the ovaries via laparotomy. No sign or symptom of recurrence was observed 5 years later. The coexistence of benign metastasizing leiomyoma in the lung and retroperitoneum following surgery for conventional leiomyomas has rarely been reported. Further, the nature and etiology of benign metastasizing leiomyoma are still not well understood. This case is therefore worth reporting, and exploring its etiology is important.

[Surgical treatment of retroperitoneal sarcomas]. / A retroperitoneális sarcomák sebészi kezelése.

Retroperitoneal sarcomas make up 0.15% of all solid tumors. The mainstay of their treatment is surgical resection, though the removal of the often sizable tumors may pose serious challenge to surgeons. There is no clear-cut recommendation for neoadjuvant, nor for adjuvant treatment so far. We collected the data and recommendations concerning the attributes and the treatment options for retroperitoneal sarcomas. Mainly we focused on the possibilities and the recent change in tactics of surgery. There is no prospective randomized study dealing with surgical treatment of retroperitoneal sarcomas. According to data in the literature the en-block R0 resection along with all the possibly involved neighboring organs offers the best chance for cure. The greatest problem is to define the required resection margin which is needed for R0 resection. Radio- and/or chemotherapy can be used for diminishing the possibility of tumor recurrence. The greatest risk factors for recurrence are incomplete resection, high grade tumor, and non-liposarcoma type histology. Survival depends on local recurrence rather than on distant metastases. Retroperitoneal sarcomas are ideally treated in sarcoma centers, where multidisciplinary consultation is available and complex treatment plans can be set. Complete recovery can be achieved with radical surgical excision. The chance for R0 resection is enhanced by chemo- and radiotherapy.

[Role of radiotherapy in the treatment of retroperitoneal soft tissue sarcomas]. / A sugárterápia szerepe a retroperitoneális lágyrészszarkómák kezelésében.

Soft tissue sarcomas are rare tumors, composing 1% of all malignancies. Fifteen percent of them are situated in the retroperitoneal region. The primary curative treatment for this group of patients is complete surgical resection. In most cases, due to their large size and localization at diagnoses, complete resection (R0) is not feasible. The main cause of disease-specific death is local recurrence. Therefore, improved local control by radiotherapy (RT) may contribute to better survival results. Based on international studies, despite the frequent positive surgical margins, only 25% of the patients with retroperitoneal sarcoma (RPS) receive perioperative RT. We performed a literature review based on the available data on the role of RT in the management of RPS. The 5-year local recurrence-free survival after surgery alone, and surgery + RT has been reported in the range of 23-54% and 40-62%, respectively. The respective 5-year rate of overall survival was of 33-49% and 48-64%. There are no available results from prospective randomized studies comparing surgery to surgery + RT. The majority of studies were retrospective and the treatments were performed over a time span of several decades. The total dose, technique and timing of RT were not standardized. Gastrointestinal and genitourinary side effects of RT are common, but their incidence and severity can be significantly reduced by using modern techniques. Based on the currently available studies, RT improves local control and it may play a role in the prolongation of overall survival as well. However, prospective randomized studies are needed to clarify the role of RT in the multidisciplinary management of RPS.

[The role of spiral computed tomography in planning the surgical interventions for non-organ retroperitoneal tumors].

The surgical operation is a principal and in most cases a solitary treatment for non-organ retroperitoneal tumors. High risk of recurrence, aptitude to large local extension dictates necessity of individual surgical plan. An equality of approach is excluded. Pre-operative specified diagnostics of tumor extension is extremely important. We present an experience of determination of such characteristics of non-organ retroperitoneal tumors, which influence the extent of surgery (multiple lesions, invasion of adjacent vessels and organs).

[Surgery and postoperative radiation therapy in primary retroperitoneal sarcomas: experience of the cancer centre Alexis-Vautrin]. / Intérêt de la radiothérapie postopératoire dans la prise en charge des sarcomes rétropéritonéaux primitifs : expérience du centre Alexis-Vautrin.

PURPOSE: Surgical resection remains the standard treatment for patients with resectable retroperitoneal sarcomas. The aim of this study was to retrospectively analyse the outcomes of patients with primary retroperitoneal sarcoma. PATIENTS AND METHODS: We analysed data of 50 patients with primary retroperitoneal sarcoma who underwent curative-intent resection from 1975 to 2008. External beam radiotherapy and chemotherapy were delivered postoperatively. Demographics, surgical, pathological variables and chemo/radiation therapy were analysed as prognosis factors. RESULTS: There were 22 males and 28 females (mean age 54 ± 13 years). Surgery required visceral resections in 30 patients. There were 16 leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients had clear surgical margins. Twenty-eight patients received postoperative external beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1 resection group (n=36). Postoperative external beam radiotherapy tends to increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05). The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years, respectively. Although R0 resection (P=0.01), well tumour differentiation (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly influenced overall survival in univariate analysis, only R0 resection was an independent prognostic factor in a multivariate analysis. CONCLUSION: We confirm the pre-eminence of radical surgery with negative margins as major prognostic factor and the benefit of postoperative radiotherapy.

Primary vs. post-chemotherapy retroperitoneal lymph node dissection (RPLND) in patients with presence of teratoma at orchiectomy.

OBJECTIVE: The presence of teratoma in the primary orchiectomy specimen creates controversies for subsequent management. Although predominant teratoma is less likely to metastasize, teratoma in the retroperitoneum may be less amenable to chemotherapy. In order to elucidate the issues about teratoma in the primary tumor, we reviewed differences between primary retroperitoneal lymph node dissection (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND) in patients with teratoma at orchiectomy. MATERIALS AND METHODS: Patients who had undergone RPLND at our institution from 2001 to 2008 were identified, and clinical charts reviewed. Eighty-three patients with teratoma at orchiectomy were identified and perioperative data were obtained. RESULTS: Of the 83 patients with teratoma at orchiectomy who underwent RPLND, 44 (53%) and 39 (47%) underwent primary and PC-RPLND, respectively. Median follow-up was 1.4 years. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were 19 (43%) positive lymph nodes for P-RPLND, of which 13 (30%) contained teratoma. For the PC-RPLND group, 30 (77%) of lymph nodes were positive, of which 28 (72%) contained teratoma. There were 3 (4%) recurrences overall, all of which recurred in the PC-RPLND group. There were 11 (13%) perioperative complications total. There were no deaths in either group. CONCLUSIONS: Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND.

Pattern of retroperitoneal dissemination of primary peritoneum cancer: basis for rational use of lymphadenectomy.

INTRODUCTION: The rationale for lymphadenectomy in primary peritoneal cancer (PPC) is unclear. We sought to define the pattern of lymphatic metastasis in PPC and propose evidence-based rationale for lymphadenectomy in relevant cases. METHODS: Patients with PPC undergoing primary surgery at Mayo Clinic were identified. Demographics, tumor characteristics, procedures performed and follow up were analyzed. RESULTS: Forty eight patients with PPC were identified; 39 had stage IIIC (81.2%) and 9 (18.8%) had stage IV. Residual disease (RD) after primary surgery was microscopic in 6 cases (12.5%), less than 1 cm in 33 (68.8%), more than 1 cm in 9 patient (18.7%) with median survivals of 5.8, 3.2 and 1.3 years, respectively. Overall, 24 patients had lymphadenectomy performed (pelvic (PND) or paraortic (PAND) or both). Pelvic nodes were involved in 12/23 (52.7%) cases, while para-aortic nodes were involved in 5/21 (23.8%) of cases. The rate of simultaneously positive pelvic and para-aortic nodes was 20% (4/20). Nodal involvement was a poor prognostic factor with 5 year overall survival 63% vs. 25% (p=0.014) in node positive vs. negative cases. Compared to patients with primary ovarian cancer (OC), OC cases had a higher rate of positive para-aortic nodes (57.6%: 77/132; p=0.004). CONCLUSIONS: Retroperitoneal lymph nodes are a common site of metastases in PPC, therefore it is logically consistent to perform PND and PAND if a patient can be cytoreduced to microscopic RD in other sites or remove grossly positive nodes in patients with RD<1 cm.

Mielolipoma retroperitoneal / Retroperitoneal myelolipomas

El retroperitoneo es el espacio que se encuentra delimitado: por detrás, por la columna lumbar y los músculos psoas ilíaco y el cuadrado lumbar; por delante, por el peritoneo parietal posterior; por arriba, el diafragma; por debajo, el piso pelviano. Los tumores retroperitoneales representan el 1,8 por ciento del total de los tumores abdominales en nuestro servicio. Los mielolipomas comprenden el 0,08-0,4 por ciento de los mismos, siendo ellos tumores benignos compuestos por tejido adiposo y hematopoyético (incluye colonias eritroides, mieloides y megacariocíticas. El objetivo de este trabajo es definir alternativas terapéuticas en tumor benigno retroperitoneal

Neuroblastoma detected by mass screening: the Tumor Board's role in its treatment.

Japan has a nationwide mass-screening program for neuroblastoma in 6-month-old infants. Neuroblastoma can regress spontaneously, and some institutions observe selected cases. We evaluated the management of screened neuroblastoma at our hospital since 1997 when an observation program was introduced. Criteria for the observation program were stage-I, stage-II, or stage-IVs tumors, urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels <40 microg/mg creatinine, tumor <5 cm in diameter, no invasion to the intraspinal canal or great vessels, and parental consent to participate. Patients who did not meet observation criteria underwent surgery or mild chemotherapy according to the location of the tumor. If patients met observation criteria after chemotherapy, surgical intervention was no longer performed. Thirty-six patients attended our hospital for screened neuroblastoma from 1997 to 2002. Thirty-three patients who were managed at our hospital participated in this study. Ten subjects met observation criteria. Tumors regressed in 7 patients (mean follow-up period 36.3 months) with corresponding decreases in VMA and HVA levels (group A). Three underwent surgery (group B) because of increasing VMA and HVA levels, increase in tumor size, or guardian's request. Twenty-three subjects did not meet observation criteria. Four patients underwent primary surgery (group C), and 19 patients had chemotherapy initially. Fourteen patients met observation criteria after chemotherapy and two are still having chemotherapy (group D). Three patients required surgery due to insufficient regression of their tumors (group E). Fourteen subjects in group D had marked decreases in VMA and HVA levels and tumor size (mean follow-up period 29.1 months), and tumors were not detected using imaging techniques in 8 patients. Histological examination of all resected specimens during the study period showed favorable histology and no N-myc amplification. There was no evidence of unfavorable prognosis in any of the 33 subjects, although 1 patient who underwent primary surgery had a vanishing kidney 1 year later and 1 patient had multiple bony metastases after complete resection of tumor, which was treated by chemotherapy. Until the real significance of mass screening for neuroblastoma as a public health measure is confirmed, observation with careful follow-up should be adopted more extensively because it has a favorable outcome in many cases, and is associated with minimal therapeutic complications.

Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis.

BACKGROUND: The purpose of this study was to develop a reliable model to identify clinical Stage I nonseminomatous germ cell tumors (NSGCTs) associated with low risk or high risk for occult retroperitoneal metastasis, so that the model could be used to customize the therapeutic approach for patients with these tumors. The model was to be based on pathohistologic parameters and immunohistochemical expression of proliferation markers, proteases, and adhesion molecules in the primary tumor. METHODS: One hundred forty-nine patients with clinical Stage I NSGCTs underwent retroperitoneal lymphadenectomy and were included in the study. Three to five paraffin embedded, formalin fixed tissue blocks were available from each patient and were analyzed for the following histopathologic features associated with pathologic Stage I or II disease: the presence or absence of vascular invasion (VI), the presence or absence of tunic invasion, and the percentage of each histologic type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D, and E-cadherin was evaluated using a semiquantitative scoring system. Statistical analysis was performed with univariate and multivariate logistic regression models. RESULTS: The percentage of embryonal carcinoma (%EC, P < 0.001) and the presence of VI (P < 0.0001) and tunic invasion (P < 0.002) were the most significant independent risk factors associated with pathologic Stage II disease. A combination of %EC and VI allowed correct prediction of final pathologic stage for 88% of clinical Stage I patients. Cutoff values including both variables identified the correct pathologic stage for 131 of 149 patients (88%). Less than 45% EC and the absence of VI correctly identified pathologic Stage I disease in 91.5% of patients; more than 80% EC and the presence of VI correctly predicted pathologic Stage II in 88%. In univariate analysis, only p53 (P < 0.03) and E-cadherin (P < 0.001) expression were significantly different in the embryonal carcinoma component of pathologic Stage I and II NSGCT. To evaluate prospectively the clinical utility of the new derived cutoff points, the data were applied to 10 consecutive patients with clinical Stage I NSGCT who underwent retroperitoneal lymphadenectomy; pathologic Stage I and II were correctly predicted for 5 of 6 Stage I and 4 of 4 Stage II patients, respectively. CONCLUSIONS: %EC and the presence or absence of VI appear to be reliable prognosticators to identify patients at high risk and low risk for occult retroperitoneal disease. In cases of clinical Stage I NSGCT, p53, bcl-2, MIB-1, cathepsin D, and E-cadherin did not appear to be of prognostic significance. The authors recommend that all patients with clinical Stage I NSGCT have their primary orchiectomy specimens evaluated for %EC and the presence of VI to determine their risk for occult retroperitoneal metastasis.

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

B7-1 expression decreases tumorigenicity and induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecules.

Neuroblastoma may escape an immune attack by virtue of its low expression of surface accessory molecules essential in the antitumor response. Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LB7-1SN to examine the influence of B7-1 expression on the immune response directed against a low major histocompatibility class (MHC) I and class II negative, B7-2, and ICAM-1 negative tumor. Using a retroperitoneal model for implantation of neuroblastoma in its natural site, we demonstrated that expression of B7-1 by neuro-2a reduces its tumorigenicity. Coinjection of B7-1-positive and -negative cells improved survival compared with mice receiving B7-1-negative cells alone. This was dependent on the ratio of B7-1+ to B7-1- neuro-2a cells injected. CD8+ and not CD4+ T-cell depletion significantly increased tumor-induced mortality in syngeneic A/J mice, indicating that B7-1 decreases tumorigenicity primarily by direct constimulation of CD8+ T cells. Rejection of N-2a/B7-1 tumors or preimmunization with irradiated N-2a/B7-1 cells die not increase protection to challenge with unmodified neuro-2a cells over mice vaccinated with N-2a/neo. Furthermore, cytotoxic T lymphocyte (CTL) precursor frequencies were not significantly higher after in vivo priming and in vitro stimulation with irradiated N-2a/B7-1 compared with N-2a/neo, indicating that B7-1 costimulation by the tumor, in the absence of adequate antigen presentation by MHC molecules, may limit the generation of effective CTLs.

Surgical treatment of clinical stage A nonseminomatous testis cancer.

Until clinical staging improves, patients presenting with clinical stage A nonseminomatous testis cancer should be offered the option of initial nerve-sparing RPLND versus surveillance. Either method of management may be successful in the individual patient. We feel each patient with clinical stage A disease must be informed of alternative methods of management and be allowed to choose the method of management that he feels best suits his needs in terms of risk benefit.

Problems of mass screening for neuroblastoma: analysis of false-negative cases.

The Japanese mass screening (MS) system for neuroblastoma at 6 months of age has resulted in the earlier diagnosis of the tumor with excellent therapeutic results. However, some problems are involved in the present MS system. We present six false-negative cases, ages ranging from 1 year 11 months to 3 years 11 months. Neuroblastoma cell taken from four of these patients were studied biologically. These patients had advanced disease (one was stage III; five were stage IV). Three of the patients have died and one is terminally ill despite undergoing surgery combined with intensive chemotherapy. Cytogenetic analysis performed in three cases showed that all the cases had diploid chromosome mode associated with 1P-, double minutes (DMs), or marker chromosomes. N-myc oncogene analysis, performed in four cases, showed amplification in two; one patient had diploid chromosomes, but the other was not examined cytogenetically. These findings were strikingly different biologically from those of cases found by MS. The majority of neuroblastomas detected by MS were found to be triploid tumors without N-myc amplification. These findings suggest that the main reason for the false-negative results in the patients we examined is that they were tumor-free or the tumors were so small in size that they were unable to produce urinary vanillylmandelic acid and or homovanillic acid levels high enough to be detected at the time of MS. Therefore, we conclude that MS at 6 months of age is too early to detect neuroblastoma with a diploid chromosome mode and/or amplified N-myc oncogene. We propose that MS at the age of 1 year 6 months would be more effective to pick up these cases, because treatment strategies depend on the different biological characteristics of tumor cells.

Radiation therapy for nonseminomatous germ cell tumors of the testis: a reappraisal.

We analyzed the efficacy of radiation therapy and retroperitoneal lymphadenectomy preceded and followed by radiation therapy as curative treatment in 113 patients with clinical stages I and II nonseminomatous germ cell tumors of the testis. Radiation therapy alone was curative in 86 and 82 per cent of the patients with clinical stages I and II disease, respectively, and radiation therapy before and after retroperitoneal lymphadenectomy was curative in 89 and 73 per cent of patients with clinical stages I and II disease, respectively. Of 26 patients with clinical stage II disease in the group receiving radiation therapy before and after retroperitoneal lymphadenectomy only 13 (50 per cent) had pathologic documentation of retroperitoneal metastasis or histologic evidence of nodal metastases that had been destroyed by radiation therapy alone. When analyzed by pathologic stage radiation therapy before and after retroperitoneal lymphadenectomy was curative in 91 and 51 per cent of patients with stage I and II disease, respectively. In our series clinical overstaging may have been responsible for the favorable results of radiation therapy alone, and radiation before and after retroperitoneal lymphadenectomy in the treatment of clinical stage II nonseminomatous germ cell tumors.