Pre-operative irradiation for retroperitoneal liposarcoma: results of a pilot study.

PURPOSE: The aim of this study was to evaluate toxicity and benefit of an original method of preoperative irradiation combined with adequate surgery in the treatment of retroperitoneal liposarcoma. Instead of irradiating the whole tumor volume, 50Gy in 25 fractions was delivered to the posterior part of the tumor and the contact zone with the postero-lateral abdominal wall only. METHODS: Between mid-2000 and end of 2011, 29 patients were included in this study, 22 with a primary tumor, 7 with a first local recurrence. The results obtained were compared with a well-matched control group operated on by the same surgeon during the same period. RESULTS: This therapy was well tolerated by all included patients and no difference in toxicity was found between pilot and control group. With a median follow-up of 84 months the oncological results were similar in both groups with a 5 y disease specific survival of 79 and 81% (p: 0.61). However a very significant difference was found according to histotype: five year disease specific survival was 84% (CI 66-93) for the well- differentiated and only 35% (CI 20-51) for the dedifferentiated liposarcoma (p < 0.0001). CONCLUSIONS: This form of combined treatment is well tolerated but superiority could not be demonstrated. Our experience clarifies some of the difficulties facing a randomized clinical trial on this topic.

Pelvic exenteration: long-term oncological results in a series of 106 patients.

INTRODUCTION: The aim of this retrospective study is to present the oncological results obtained in a series of 106 patients who underwent a pelvic exenteration with curative intent. PATIENTS AND METHODS: Between December 1980 and December 2008 pelvic exenteration was performed in a series of 106 patients, in 69 for gynecologic cancer, in 29 for colorectal cancer, in 6 for urological and in 2 for skin cancer. In only 21 patients it was the primary treatment, in 85 it was for persistent or recurrent tumor. The resection was macroscopically complete in all patients. RESULTS: Overall five-year and ten-year survival was 40% and 33% respectively, disease-free survival 41 and 37%. Survival was better for gynecological tumors than for the other tumors. After supralevatoric exenteration survival was 50% and 47% and better than after infralevatoric exenteration. Exenteration with extension beyond the classical plane of dissection resulted in a 5 year survival of 32%. The only significant difference found was according to the margin status. After R1 resection the median survival was 24 months and the 5-year survival only 9% whereas R0 resection resulted in a 5-year survival of 47% and a local recurrence rate of 13.5%. Fifteen patients died from an unrelated cause. Only 12% of the patients alive 5 years after the operation suffered from recurrent tumor and surgery cured half of them. CONCLUSION: Pelvic exenteration in patients with advanced or recurrent pelvic cancer results in a long-term cure rate of about 50% if an R0 resection has been obtained.

Handling ovarian cancer FIGO III-IV : evolution over the last 30 years.

The treatment of ovarian cancer FIGO III-IV has undergone substantial changes in the last 30 years. As I was involved as an oncological surgeon in the treatment of these patients since 1979 and made my PhD thesis on this subject, I consider myself a privileged witness of this evolution. In the late 1970's two major changes took place: the introduction of combination chemotherapy containing cisplatin and the concept of debulking surgery. In 1980 we embarked on an ambitious treatment plan combining maximal cytoreductive surgery, 6 cycles of chemotherapy, second look laparotomy and panabdominal irradiation. The results were analyzed in 1991 and gave rise to the following changes. Surgical cytoreduction could only be considered optimal if no residual tumor was left and residual tumor correlated with median survival. Upfront surgery was abandoned in FIGO IV and FIGO III with a very high tumor load. Panabdominal irradiation was too toxic. A recent randomized study has established equivalency of survival in FIGO IIIc between interval debulking after 3 cycles and upfront surgery. Initial tumor load remains a determinant of long- term cure and optimal upfront surgery is critical in patients with a metastatic tumor load of less than 100 gram. Retroperitoneal node dissection becomes important when complete resection of peritoneal metastases can be obtained. In experienced hands selection for primary debulking or for interval debulking seems possible at laparoscopic exploration.

V-Y Bilateral gluteus maximus myocutaneous advancement flap in the reconstruction of large perineal defects after resection of pelvic malignancies.

OBJECTIVE: To evaluate the role of the V-Y bilateral gluteus maximus myocutaneous flap (GLM) in the reconstruction of large perineal defects after wide surgical resections for pelvic malignancies. METHOD: Twelve consecutive patients (seven females and five males), of mean age 59 years (36-78), with primary or recurrent pelvic malignancies (rectal, anal and vulvar carcinoma), underwent either abdomino-perineal rectum excision with partial sacrectomy or total pelvic exenteration. The perineal defect was reconstructed by means of a GLM flap. Intra-operative blood loss, operative time, hospital stay, postoperative complications and long-term outcome were retrospectively assessed. RESULTS: One patient died postoperatively. All the remaining patients had at least one early and/or late complication. After a mean follow-up of 31.2 months, seven patients were alive. No major functional impairment in daily activities was observed. Five patients experienced a slight discomfort in either walking, sitting or cycling. CONCLUSION: Gluteus maximus myocutaneus flap is a useful technique for the repair of perineo-pelvic defects after abdomino-perineal rectum excision with partial sacrectomy.

Radiation-induced sarcoma: analysis of 46 cases.

A retrospective analysis was performed of 46 cases of sarcoma treated in our institution between 1989 and 2007 that occurred in a previously irradiated area. Eight male and 38 female patients had received radiotherapy, mainly for breast cancer and genitourinary tumours. The interval between irradiation and the diagnosis of sarcoma ranged from 1 to 54 years (median 15 y). The most common clinical findings were a mass, pain and skin dislocation. Angiosarcoma and sarcoma non-otherwise-specified were the most common histological types. Surgical resection was performed in 34 patients (74%) and 5-year survival was 45% when a radical resection was obtained. No 5-year survival was noticed after non-radical resection and in the absence of surgery. Stage and location of the sarcoma were other prognostic factors. Overall 5-year survival was 27% for the whole group.

Cytogenetic characterization of tenosynovial giant cell tumors (nodular tenosynovitis).

Chromosome investigation in six localized forms of tenosynovial giant cell tumors, also known as modular tenosynovitis, revealed an identical translocation between chromosomes 1 and 2, t(1;2)(p11;q35-36) in three tumors, a variant translocation t(1;5)(p11;q22) in a fourth case, and a t(2;16)(q33;q24) in a fifth case. One case showed a normal karyotype. Although morphologically rather uniform, these benign tumors appear to be cytogenetically heterogeneous, but the chromosome changes seem to cluster in 2 regions, 1p11 and 16q24.

Infection assessment of totally implanted long-term venous access devices.

AIM: Comparison of catheter tip versus port content culture techniques to assess infection in totally implanted vascular access devices (TIVAD). MATERIALS AND METHODS: Comparison of pocket swab, catheter-tip and port content cultures after removing the silicon puncture septum in a prospectively collected consecutive series of 102 TIVAD removed for clinical suspicion of infection, between May 2000 and March 2003. RESULTS: 102 totally implanted port-catheters in 98 patients, age ranging from 1 to 90 years (median 53 years), were removed 7 to 2616 days after insertion (median 210 days). Infection of the pocket surrounding the port was found in 21 cases, all proven by a positive culture of the pocket swab. Out of the remaining 81 cases without pocket infection, 32 had only a positive catheter tip culture, whereas 56 had a positive port content culture (p = 0.0002). Always the same microorganism was isolated in the 32 patients with positive catheter tip and port content cultures. The main organisms identified within TIVAD were Coagulase Negative Staphylococcus (CNS) (41 cases) and Candida sp (15 cases). Eight out of the 21 pocket infections were caused by Staphylococcus aureus. CONCLUSION: In the presence of local signs of infection, taking cultures of the pocket surrounding the port is sufficient for diagnostic purposes. When infection is localized within the device only, port content cultures taken after removal of the silicon septum are more often positive than cultures of the catheter tip, and constitute therefore a more reliable tool for the assessment of TIVAD infection.

Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer.

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

Cytogenetic analysis of subcutaneous angiolipoma: further evidence supporting its difference from ordinary pure lipomas: a report of the CHAMP Study Group.

Subcutaneous angiolipomas are benign soft-tissue lesions consisting of two mesenchymal elements (i.e., adipose tissue and blood vessels) and having distinct clinical features. They usually are multiple, with an obvious male predominance, and hereditary occurrence has been described. Twenty subcutaneous angiolipomas from 10 patients with typical clinical and morphologic features were reviewed. All lesions had a normal karyotype. This finding is in striking contrast with ordinary lipomas, spindle-cell and pleomorphic lipomas, lipoblastomas, and hibernomas, most of which have characteristic clonal chromosomal aberrations. The normal karyotype of subcutaneous angiolipoma as well as its distinct clinical and morphologic features suggest a different pathogenesis from pure lipomas.

Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing, (a report from the CHAMP Group).

Cytogenetic analysis carried out in 28 adipose tissue tumors diagnosed microscopically as myxoid liposarcoma (ML) revealed a t(12;16)(q13:p11) chromosomal translocation in 26 of the 28 cases. Morphologically, these tumors were subclassified into the following categories: well-differentiated, six cases: poorly differentiated round cell type, 17 cases: poorly differentiated spindle cell type, five cases. Poorly differentiated ML behaved in a more aggressive fashion than the well-differentiated tumors. The results of this study confirm the consistency and specificity of the t(12;16)(q13:p11) translocation as the genetic marker of ML, support the contention that liposarcomas with round cells belong to the ML category, and confirm Stout's proposal for the existence of a poorly differentiated ML composed of spindle cells. Cytogenetic analysis may be helpful in the differential diagnosis of ML with atypical lipomatous tumors, which is characteristically associated with ring and giant marker chromosomes, and of ML with lipoblastoma, which is typically associated with 8q alterations. The existence of a mixed ML-atypical lipomatous tumor remains questionable. The genetic events associated with the greater aggressiveness of the poorly differentiated types of ML remain to be determined.

Angiomyxolipoma shares cytogenetic changes with lipoma, spindle cell/pleomorphic lipoma and myxoma.

Angiomyxolipoma is a rare variant of lipoma, two cases of which have recently been described. We report on the hitherto unreported clonal chromosomal changes of a third case of angiomyxolipoma. The karyotype showed a 46,XX,t(7;13)(p15;q14),t(8;12)(q13;p13)[17]/46,XX[3]. The involvement of 13q14, 12p13, and 8q13 supports a relationship with other types of benign lipomatous and myxoid tumors.

Is 4q13 a recurring breakpoint in solitary fibrous tumors?

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm found predominantly in the subpleural region but also in many other body sites. We report a malignant solitary fibrous tumor of the peritoneum with a 47,XY,t(4;9)(q13;p23),+5 karyotype. The chromosome 4q13 breakpoint in the presented and previously published case of pleural solitary fibrous tumor with a 46,XY,t(4;15)(q13;q26) karyotype was further characterized by fluorescence in situ hybridization analysis and localized within the 5-cM interval that was flanked by regions specific to YAC clones 761A7 and 886C11. Chromosome translocations involving chromosome 4q13 may characterize a separate cytogenetic subgroup of SFT.

New discriminative chromosomal marker in adipose tissue tumors. The chromosome 8q11-q13 region in lipoblastoma.

Specific chromosome abnormalities characterize benign and malignant adipose tissue tumors and are of great diagnostic and clinical importance. Lipoblastoma is a rare benign adipose tumor that mimics myxoid liposarcoma histologically. Although only a few lipoblastomas have been investigated cytogenetically, it is increasingly clear that these adipose tissue tumor generally show rearrangements of 8q11-q13 region but lack the t(12;16) that allows these tumors to be distinguished from myxoid liposarcomas.

Trisomies 8 and 20 in desmoid tumors.

A nonrandom occurrence of trisomy 8 and of trisomy 20 in desmoid tumors has been recently reported. The finding of trisomy 8 in nondividing desmoid tumor cells by in situ hybridization prompted us to evaluate, in a similar way, the occurrence of trisomy 20 and the possible occurrence of both trisomies together because their co-existence was cytogenetically observed in a few cases. Double fluorescence in situ hybridization (FISH) with centromeric probes for chromosomes 8 and 20 was performed on 16 single cell suspensions of desmoid tumors. FISH confirmed the occurrence of trisomy 8 or 20 in a single cell suspension of desmoid tumors. Both individual trisomies, and even more their association in the same cells, are rare to extremely rare in solid tumors in general and in mesenchymal tumors in particular, and are only known to occur in infantile fibrosarcoma.

Trisomy 21 in solitary fibrous tumor.

We found trisomy 21 as the sole chromosome abnormality in a solitary fibrous tumor arising at a nonpleural site. No cytogenetic investigation of solitary fibrous tumors has previously been reported.

A variant (2;13) translocation in rhabdomyosarcoma.

Cytogenetic analysis of a right buttock mass from a 5-year-old boy showed translocation between an inverted chromosome 1 and a chromosome 13 as the sole cytogenetic abnormality. The breakpoint 13q14 appears to be the same as in previously reported cases of rhabdomyosarcoma (mostly of the alveolar type), but does not show involvement of 2q37. We suggest that this translocation may be a variant of the classical t(2;13)(q37;q14) found in rhabdomyosarcoma.

Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors.

Cytogenetic analysis of 184 adipose tissue tumors, 175 lipomas, and nine liposarcomas (LPS) showed the presence of a ring chromosome and/or a long marker chromosome in 10 cases with common histologic features such as atypical stromal cells with or without lipoblasts. In five of the cases, this appeared to be the sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with a microclone library specific for chromosome region 12q13-q15 showed extensive staining of the ring and long marker chromosomes, indicating that genetic sequences of this particular region of chromosome 12 are present in these marker chromosomes, most likely in an amplified form.

Translocation (X;1) reveals metastasis 31 years after renal cell carcinoma.

Cytogenetic investigation of a metastatic lesion appearing 31 years after nephrectomy allowed for the diagnosis of a renal cell carcinoma. The der(X)t(X;1)(p11.2;q21.1) found in this case and review of the 14 other cases previously reported indicates that this chromosome lesion may characterize a specific subgroup of renal cell carcinoma, with distinct histology and age distribution that also can occur in females.

Comparison of chromosomal patterns with clinical features in 165 lipomas: a report of the CHAMP study group.

Soft tissue lipomatous tumors are morphologically heterogeneous. Various morphologic features are associated with specific chromosomal patterns and clinical features such as age, sex, and tumor site, location, and size. Simple lipomas are known to be karyotypically heterogeneous, but this has not been correlated with clinicopathological features. In 165 cases of solitary soft tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes were divided into the following groups: normal karyotype; 12q13-15 aberrations; 6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker chromosomes or both; other aberrations. The tumors were reexamined morphologically without knowledge of the karyotypic or clinical data. An abnormal chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%) lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64 (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients under 30 years of age than in those from older individuals (6 of 16 vs. 30 of 149, 40% resp. 20%). Apart from the finding that normal karyotypes were more common in patients younger than 30 years, there was no significant association between cytogenetic pattern and patient sex or age or tumor localization, size, or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the cytogenetic subtypes among benign lipomas remain unexplained.

Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group.

Leiomyosarcomas (LMS) of soft tissues frequently show complex karyotypic changes, and no specific aberration has been identified. The aim of this study was to search for recurrent chromosome aberrations in soft tissue LMSs and to correlate these, if present, with morphological and clinical parameters. From a series of soft tissue sarcomas thoroughly reexamined cytogenetically and histopathologically, 45 LMSs were retrieved; 35 were classified microscopically as spindle cell, 3 as epithelioid, and 7 as pleomorphic. Clonal chromosome changes were present in 14, 3, and 3 cases, respectively. This series was combined with 11 previously published, karyotypically abnormal pleomorphic LMSs for cytogenetic-clinico-histopathological correlations. The breakpoints were widely scattered, with no predilection of any of the recurrent breakpoints and losses to any of the morphologic subtypes. Combining numerical and unbalanced structural changes, the most frequently lost segments were 3p21-p23 (11 cases), 8p21-pter, 13q12-q13, 13q32-qter (10 cases each), 1q42-qter, 2p15-pter, 18p11 (9 cases each), 1p36, 11q23-qter (8 cases each), and 10q23-qter (7 cases). The most frequent gain was 1q12-q31 (6 cases). There was a greater frequency of losses in 1p and 8p and a lower frequency of losses in 10q and 13q in tumors that had metastasized than in localized tumors. We conclude that LMSs with clonal abnormalities display highly complex karyotypic changes and extensive heterogeneity. No significant correlation exists between these changes and age and sex of the patients, or with depth of tumor, topography, microscopic subtype, or tumor grade. Losses in 1p36 and 8p21-pter may be associated with increased risk of metastases. Comparison of our findings in soft tissue LMS with those previously reported in LMS in other locations suggest that the karyotypic profile is more dependent on site of origin than on microscopic features.