Andrea Cavalcanti

Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases

It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear.

Impact of Surgery on Advanced Gastrointestinal Stromal Tumors (GIST) in the Imatinib Era

BackgroundThe role for surgery in patients with “unresectable” gastrointestinal stromal tumors (GIST) treated with imatinib is still not defined. The objective of this retrospective study was to evaluate the feasibility and benefit of this secondary surgery.MethodsProgression-free survival (PFS) in a group of patients who underwent secondary surgery was compared to that of patients treated exclusively with imatinib.ResultsOf 180 patients with unresectable GIST treated with Imatinib, 22 (12%) underwent secondary surgery, following which one patient achieved a complete radiological response, 19 achieved a partial response (PR), in one patient the disease was stable, and in one patient there was reactivation of local occlusive disease after an initial PR. No patient with overall progression was to undergo surgery. At the beginning of imatinib therapy, five patients with metastases underwent emergency surgery [hemorrhage (nxa0=xa03) due to rupture of large necrotic masses], which ultimately resulted in three of the five patients dying postoperatively. A macroscopically complete resection was achieved in all primary tumors (5/5) and in ten of the 17 metastases. Pathological analysis revealed two complete response (CR) and 17 PR, and no treatment effect was evidenced in three patients. Two-year overall survival after surgery was 62%. The median PFS calculated from the initiation of imatinib therapy was 18.7 months for all operated patients and 23.4 months after planned surgery.ConclusionPrimary tumors that become amenable to surgery with prior imatinib therapy, evolving necrosis and localized progression (to avoid life-threatening complications) could benefit from this secondary surgery. For the majority of other residual lesions, the potential benefit of secondary surgery should be evaluated in randomized studies in the future since PFS is similar to that reported among non-operated patients.

Resection of liver metastases from colorectal cancer : the real impact of the surgical margin

AIMSnThe benefit of liver resection for metastatic colorectal cancer is now established. Nevertheless if the surgical margin on pre-operative imaging is considered to be less than 10 mm, this is considered an absolute contraindication to surgery by some, and a relative contraindication by others, so its real impact on prognosis is not clear.nnnMETHODSnFrom 1984 to 1996, 269 patients underwent hepatectomy for liver metastases and were prospectively studied. The only two objectives of this surgery were to be curative (or achieve complete R0 resection), and to avoid mortality. Of the 269, 187 patients had surgical margins inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had extrahepatic metastatic sites. Their clinical and pathological factors were specifically studied.nnnRESULTSnThe crude 5-year survival of these 187 patients (including the 2% post-operative mortality) was 24.7%, and the disease-free survival was 18.8%. The surgical margin was 0 mm in 60 cases and was histologically invaded in 20 cases. The most important prognostic factor was whether the resection was considered palliative (R1-R2 resection according to UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded, there was not prognostic difference between the 107 patients with a margin of 0-4 mm and the 143 patients with a margin greater than 4 mm. However, a surgical margin greater than 9 mm appears to be a second prognostic factor (P = 0.001), when these 187 patients are compared to others. The reasons behind this are that there is a close relationship between narrow margins and extensive disease (high number of metastases, bilateral localization and extended hepatectomy), and also an increased possibility of microscopic satellite lesions within 10 mm around the metastases.nnnCONCLUSIONnThe real prognostic impact of the surgical margin must not be overestimated. Hepatectomy for metastases can provide long-term survival in patients with supposed poor prognostic factors. Resection is justified so long as it is complete and with minimal risk. An experienced, specialized centre can be a prognostic determinant.

Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation.

Axillary Padding without Drainage after Axillary Lymphadenectomy – a Prospective Study of 299 Patients with Early Breast Cancer

Background: After lymphadenectomy for early breast cancer, seroma formation is a constant event requiring a suction drainage. This drainage is the strongest obstacle to reducing the hospital stay. Axillary padding without drainage appears to be a valuable option amid the various solutions for reducing the hospital stay. Methods: We conducted a comparison between 114 patients with padding and 185 patients with drainage. Data were obtained from 2 successive prospective studies. Results: The mean hospital stay was 2.4 days (range 1–4) in the padding group and 4.2 days (range 2–9) in the drainage group (p < 0.05). There were fewer needle aspirations for seroma in the padding group (8.8 vs. 23%, p < 0.05). At 6 weeks, only 28% (32/114) of the patients in the padding group reported pain versus 51% (94/185) in the drainage group. The mean pain intensity at 6 weeks was 3 and 4.3 respectively (p < 0.0001). Conclusion: Axillary padding without drainage was associated with a better post-operative course than suction drainage in this historical comparison, and the hospital stay was significantly shortened. There are only few series published on this new technique but they all indicate good feasibility and good tolerance. A large randomised multicentric evaluation is now warranted.

Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion

Cancer-associated fibroblasts (CAFs) play a central role in the complex process of tumor-stroma interaction and promote tumor growth. Emerging evidences also suggest that these fibroblasts are involved in the alteration of the anti-tumor immune response by impacting several immune cell populations, especially through their secretion of pro-inflammatory and immunosuppressive factors in the tumor microenvironment. However, the underlying immuno-modulating mechanisms triggered by these fibroblasts are still only partially defined. In this study, we provide evidence that melanoma-associated fibroblasts decrease the susceptibility of melanoma tumor cells to NK-mediated lysis through the secretion of active matrix metalloproteinases. This secretion reduces the expression of the two NKG2D ligands, MICA/B, at the surface of tumor cells and consequently decreases the NKG2D-dependent cytotoxic activity of NK cells against melanoma tumor cells. Together, our data demonstrate that the modification of tumor cell susceptibility to killer cells is an important determinant of the anti-tumor immune response alteration triggered by CAFs.

Reconstruction par lambeaux libres dans les sarcomes localement évolués

Resume But de l’etudexa0: Le but de cette etude retrospective etait d’etudier les avantages de la reconstruction par lambeaux libres apres exerese des sarcomes des tissus mous localement evolues. Patients et methodexa0: D’octobre 1997 a octobre 2000, sur un ensemble de 256 operations pour sarcome, 25 ont necessite la mise en place d’un lambeau libre de couverture. Il s’agissait de 16 femmes et neuf hommes (âge moyenxa0: 45 ans). La tumeur siegeait aux membres inferieurs ( n =xa015), superieurs ( n =xa03) et au tronc ( n =xa07), avait une taille moyenne respectivement de 12,10 et 12xa0cm, etait multifocale ( n =xa06) ou recidivee ( n =xa010). Dix patients ont recu une chimiotherapie neoadjuvante. L’exerese tumorale a necessite dans dix cas un geste operatoire complementaire. La couverture du site d’exerese a ete realisee par des lambeaux libres de grand dorsal ( n =xa021) et de grand droit ( n =xa04). Une radiotherapie postoperatoire precoce a ete realisee chez 15 patients. Resultatsxa0: La duree mediane de l’operation a ete de 6 heures 30. Il n’y a eu aucun deces postoperatoire. Deux lambeaux ont necrose, ce qui a necessite la confection d’un second lambeau. L’exerese etait R 0 (n =xa020), R 1 ( n =xa04), R 2 ( n =xa01). Avec un recul median de 20 mois, aucun patient R 0 n’avait de recidive locale. Dix patients (40xa0%) ont eu des metastases pulmonaires et cinq d’entre eux etaient decedes. Conclusionxa0: L’utilisation d’un lambeau libre a permis de realiser une exerese plus large du sarcome, d’eviter l’amputation d’un membre chez 14 patients et d’envisager une irradiation postoperatoire precoce chez 15 patients. La prise en charge multidisciplinaire et la collaboration entre chirurgien oncologue et plasticien permettent d’ameliorer le pronostic des sarcomes des tissus mous localement evolues.

Trabectedin in advanced desmoplastic round cell tumors: a retrospective single-center series

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy that occurs with unpredictable chemosensitivity and limited treatment options in the advanced setting. Prognosis is poor, and exploring new treatment options for such diseases is difficult because of its rarity. Clinical activity of trabectedin for advanced DSRCT was scarcely reported in the literature. Here, we report a series of six patients treated with trabectedin for an unresectable DSRCT. After receiving trabectedin, two patients had stable disease with a time to progression of 3 and 3.5 months; four patients experienced disease progression after one cycle, two of them could receive one and two patients another line regiment. Four patients experienced grade 3–4 adverse events, two grade 3 thrombocytopenia, and one neutropenic fever. Prognosis was poor with a median overall survival of 4 (range: 2–14) months. In our experience, trabectedin had limited activity in advanced DSRCT. Further studies are warranted to find effective treatments.

Vinorelbine-based chemotherapy in metastatic epithelioid sarcoma.

e22549Background: Epithelioid sarcoma (ES) is a rare soft tissue sarcoma subtype, with poor and short-term responses to conventional, doxorubicin-based chemotherapy (Jones et al, Am J Clin Oncol 20...