Landmark Series: A Review of Landmark Studies in the Treatment of Primary Localized Retroperitoneal Sarcoma

Annals of Surgical Oncology - Primary localized retroperitoneal soft tissue sarcomas (RPS) have shorter survival than other soft tissue sarcoma sites owing to higher local recurrence rates...     

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 1. Nonaccidental mortality

This study was undertaken to determine whether variations in concentrations of particles in the ambient air of Montreal, Quebec, during the period 1984 to 1993, were associated with daily variations in nonaccidental mortality. Fixed-site air pollution monitors in Montreal provided daily mean levels of various measures of particulates and gaseous pollutants. Total sulfates were also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec). We estimated associations for PM(2.5), PM(10), total suspended particles, coefficient of haze (COH), extinction coefficient, and sulfates. We used coefficient of haze, extinction coefficient, and Sutton sulfates to predict fine particles and sulfates for days that were missing. To estimate the associations between nonaccidental mortality and ambient air particles, we regressed the logarithm of daily counts of nonaccidental mortality on the daily mean levels for the above measures of particulates, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and gaseous pollutants. There were 140,939 residents of Montreal who died during the study period. We found evidence of associations between daily nonaccidental deaths and most measures of particulate air pollution. For example, the mean percentage increase (MPC) for an increase of total suspended particles of 28.57 microg/m(3) (interquartile range, IQ), evaluated at lag 0 days, was 1.86% (95% confidence interval (CI): 0.00-3.76%), and for an increase of coefficient of haze (IQ=18.5 COH units per 327.8 linear m) the MPC was 1.44% (95% CI: 0.75-2.14%). These results are similar to findings from other studies (the mean percentage increase in nonaccidental deaths for a 100 microg/m(3) increase in daily total suspended particles was 6.7%). We also found increases for fine particles and for inhalable particles, but the confidence intervals included unity. All measures of sulfates showed increased daily mortality; e.g., the MPC for sulfates from fine particles (IQ=3.51 microg/m(3)) was 1.86% (95% CI: 0.40-3.35%). We generally found higher excesses in daily mortality for persons 65 years of age and for exposures averaged across lags 0, 1, and 2 days. The slope of the association between daily mortality and ambient air particles in Montreal, which has lower levels of pollution than most major urban centers, is similar to that reported in most other industrialized cities. This study therefore provides further evidence that the association is linear and that any threshold effect, should it exist, would be found at lower levels of air pollution than those found in Montreal.     

Pressure-suit combined with pelvic stop-flow: a feasibility study in a bovine model.

BACKGROUND: Isolated pelvic perfusion exposes tissue to high drug doses and may benefit patients with advanced malignancy. However, leakage is a limit to this technique. AIMS: The aim of the study is to increase the perfusion ratio between local and systemic compartments on isolated pelvic perfusion. We hypothesised that an inflated pressure-suit placed above the level of aortic and caval stop flow could decrease leakage from the regional to the systemic blood compartment in a bovine model. METHOD: As the size of the pressure-suit was adapted for use in humans, we performed our experimental study on 6 calves which are big enough to fit into the suit. We used an inflated pressure-suit placed at low (40mmHg) and high pressures (125mmHg) above the level of aortic and caval stop-flow. A pharmacokinetic study with cisplatinum was performed in both compartments. RESULTS: After injection of the drug, the mean ratio of drug concentration in the locoregional/systemic compartment was 43.1. After 30min, this mean ratio was 4 and 9.7 for a pressure-suit pressure of 40mmHg and 125mmHg, respectively. At pressure-suit pressures of 40mmHg and 125mmHg, pelvic perfusion achieved pelvic/systemic exposure ratios of 5.9 and 14.9 at 30min, respectively. Leakage at 30min was higher when the pressure-suit was inflated at low pressure (40mmHg, mean 18%). When the pressure-suit was inflated at high pressure, leakage was lower (125mmHg, mean 7%). CONCLUSIONS: The pressure-suit increased the perfusion ratio between pelvic and systemic compartments in a bovine model.     

Treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate post-operative intraperitoneal chemotherapy: feasibility and preliminary results

BACKGROUND/AIMS: Peritoneal carcinomatosis (PC) discovered during hepatectomy is usually a contraindication to resection. A potentially efficient treatment of PC is the resection of the macroscopic disease and the treatment of the residual microscopic disease with immediate post-operative intraperitoneal chemotherapy (IPIC) (before the entrapment of cancer cells inside the fibrin deposit which rapidly cover the injured tissues). Feasibility and survival results of this treatment, combined with major hepatectomy, have never been evaluated. The purpose of this study is to report tolerance and preliminary results in patients with liver metastases synchronous to moderate PC, treated with hepatectomy, complete cytoreductive surgery, and IPIC. METHODOLOGY: Twelve patients with liver metastases and moderate PC from miscellaneous origins, underwent: 1) hepatectomy (9 of them were major hepatectomies); 2) complete cytoreductive surgery of the PC resecting between 20 and 150 nodules; and, 3) IPIC, for 5 days, according to histology. RESULTS: There was no mortality. Morbidity was mainly due to four transient biliary leakages (33%) and there was no systemic complication due to the chemotherapy. After a median follow-up of 14.4 months, there was no detectable recurrence of the PC. Preliminary results concerning survival are promising with 7 patients without recurrent disease. CONCLUSIONS: When a minimal or moderate PC is discovered during laparotomy for liver resection of metastases, the combination of hepatectomy with complete cytoreductive surgery of the peritoneal disease, followed with IPIC is logical and feasible. This aggressive treatment is well tolerated although the frequency of biliary leakage seems to be higher than that after standard hepatectomy. No recurrence of the peritoneal disease was detected and survival results are very promising.     

Retroperitoneal sarcomas: 2. Surgical and complementary treatment]

Retroperitoneal sarcomas are often voluminous tumors which spread via diverse anatomic paths. The resulting difficult excision explains the high frequency of local or peritoneal recurrence (80% at 10 years). Controlled, complete wide surgical excision is essential as repeated local recurrence is the usual cause of death. The main prognostic factors are the quality and extent of the surgical excision, the histopathology grade, and the metastatic extension. Peroperative pathology is indispensable as no imaging method can provide a sure differentiation between benign and malignant retroperitoneal tumors. CT-scan and MRI are useful to assess extension of the sarcoma to neighboring organs. Surgical treatment should be well-controlled with resectability criteria established preoperatively. A pseudo-capsule limiting the tumor should not be considered as a sufficient safety margin. Extension to neighboring organs is an essential element in preventing the risk of local recurrence. This extension may necessitate associating different access routes. The vascular element must be carefully assessed due to the major problems of reconstruction encountered in subperitoneal tumors, particularly in women. The role of neo-adjuvant chemotherapy has not been well-determined but pre and postoperative chemotherapy protocols currently under investigation have shown objective response. Intraoperative or postoperative adjuvant radiotherapy is also under evaluation. Operated patients should be followed regularly as the risk of recurrence is high. Surgery is indicated for the treatment of recurrences with the best results being obtained after early detection. PET and FDG explorations may be useful for detecting recurrence early.     

Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases.

BACKGROUND: The aim of this study was to prospectively evaluate the use of Doppler ultrasonography with perfusion software and contrast agent injection (DUPC) during isolated limb perfusion (ILP) with high-dose chemotherapy and TNF-alpha(biochemotherapy) in patients with locally advanced extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: Fifty-two patients were prospectively included in this monocentric imaging trial. Three were excluded because the study was incomplete in two patients and one tumour did not exhibit any contrast uptake. DUPC was performed before ILP and on days 1, 7, 15, 30 and 60 after ILP. A total of 292 DUPC were performed on 55 target lesions in 49 evaluable patients. The percentage of contrast uptake was evaluated at each tumour site by two radiologists. The criterion tested was a decrease of more than 50% in intra-tumour contrast uptake compared to the pre-ILP examination. Results were compared with both MRI and histological analysis after resection of residual disease. RESULTS: According to MRI and the histological analysis, 25 (51%) patients were good responders (no difference between the four treatment arms) with tumour necrosis exceeding 90% and 24 (49%) were poor responders. As of day +1, the accuracy of DUPC in predicting tumour response was 82% (18/25 good responders and 22/24 poor responders) increasing to 91% at day +7, 95% at day +15 and 96% at day +30. At day +15, DUPC was predictive of a good response in 100% of the cases. CONCLUSION: DUPC is a simple technique, allowing early prediction of tumour response after ILP. A new treatment planning scheme can be proposed based on the results of this study.     

Current findings on gastrointestinal stromal tumors: seven observations of malignant tumors

PURPOSE: Gastrointestinal stromal tumors (GIST) are rare neoplasms, 1-3% of malignant gastrointestinal tumors. They are immature proliferations of spindled and/or epithelioid cells, developed in the muscular layer of the digestive tract, showing uncompleted or partial muscular, nervous or mixed differentiation. Immunohistologic knowledge about these tumors has recently progressed because of the discovery of specific markers (coexpression vimentin-CD117, oncogenes): GIST can now be distinguished from the other mesenchymal tumors. METHODS: Retrospective study of seven patients with GIST who received the same treatment. RESULTS: For our seven patients the mean age was 49 years with a male predominance (sex-ratio 4/3). The tumoral localisations are principally the small bowel (four cases), the rectum (two cases) and the stomach (one case). The treatment consisted of a first surgery, adapted to the tumoral localisation and extension, associated to chemotherapy in case of metastasis or local recurrence. The study of the histological grading for the seven patients showed tumors with poor prognoses. Six patients developed recurrence in a 2-year period; for the survey we are too close for a proper view. CONCLUSIONS: A review of the literature on stromal tumors finds older patients (59 years) with an equal sex ratio. Against the results of our series, the most frequent location is the stomach (50%). But the main problem is the better understanding of the particular evolution of these tumors. The bad short-date prognosis imposes carrying out larger studies, in order to confirm the principal hypothesis of histogenesis and to improve the survey by an optimal treatment.     

Neoadjuvant chemotherapy in sarcoma

This document describe s the proposed clinical practices guidelines for neoadjuvant chemotherapy in soft tissue sarcomas proposed by the French Sarcoma Group.Neo-adjuvant chemotherapy remains an experimental therapeutic procedure in soft tissue sarcomas. Neo-adjuvant chemotherapy may be proposed in three different types of situations: 1) a locally advanced tumor, non accessible to R0 or 1 removal of the lesion. Its objective is there to allow for R0 or R1 surgical removal of the tumor. 2) A locally advanced tumor, accessible to R0 or 1 removal of the lesion, but with a mutilating surgery (amputation). Its objective is there to allow for R0 or R1 conservative surgical removal of the tumor. In both situation, the strategy should be discussed beforehand in a multidisciplinary specialized consultation for sarcoma. 3) In the case where complete (R0 or R1) surgical removal of the tumor can be performed, neooadjuvant chemotherapy has no demonstrated role. The only randomized phase III clinical trial testing neo-adjuvant chemotherapy in this setting, i.e. the STBSG 62871 STBSG trial, failed to demonstrate any benefit in terms of overall or progression free survival. The selection of the type of chemotherapy regimen given in the neoadjuvant setting should be discussed in a multidisciplinary setting, considering the age and the general status of the patient; young patients, without associated concomittent illnesses should be proposed for a combined chemotherapy regimen, combining doxorubicin (> or = 50 mg/m2) and ifosfamide (> 5 g/m2) on the basis of randomized trials demonstrating an improvement of response rate versus single agent therapy with doxorubine. In elderly and/or frail patients, conversely, single agent doxorubicin may be the preferred option.