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- Belgrano, Valerio, et al.
(författare)
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Response and Toxicity of Repeated Isolated Limb Perfusion (re-ILP) for Patients With In-Transit Metastases of Malignant Melanoma.
- 2019
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Ingår i: Annals of surgical oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 26:4, s. 1055-1062
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Tidskriftsartikel (refereegranskat)abstract
- Isolated limb perfusion (ILP) is a safe and well-established treatment for in-transit metastases of melanoma. In case of relapse or disease progression, ILP can be repeated (re-ILP). This study aimed retrospectively to analyze a large consecutive series of re-ILP and compare clinical outcomes with first-time ILP.Between 2001 and 2015, 290 consecutive patients underwent 380 ILPs. Of these, 90 were re-ILPs including 68second ILPs, 16 third ILPs, 4 fourth ILPs, and two fifth ILPs. The study evaluated response (using World Health Organization [WHO] criteria), local toxicity (using the Wieberdink scale), and complications (using Clavien-Dindo).The results were compared between the first ILP, the second ILP, and the third to fifth ILP. The overall response rate was respectively 83%, 80% and 68%, with a complete response (CR) rate of 60%, 41%, and 59%. In the re-ILP group, the patients with a CR after the first ILP had a 65% CR rate after the second ILP compared with 8% for the patients without a CR (p=0.001). The risk for local toxicity or complications was not increased after re-ILP. The median overall survival periods were respectively 34, 41, and 93months (p=0.02).As a therapeutic option, ILP can be repeated safely for in-transit metastases of melanoma, achieving similar high response rates without increasing complications or toxicity. Re-ILP is mainly indicated for patients who already had a CR after the first ILP, whereas other treatment options should be considered for primary non-responders.
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- Bjersand, Kathrine, et al.
(författare)
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Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 22, s. S810-S816
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic drugs, we investigated the basis for IPC drug selection and the role of IPC in the management of PMP.METHODS: Tumor cells were prepared by collagenase digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was correlated to progression-free survival (PFS) and overall survival (OS).RESULTS: Samples from 92 patients were analyzed successfully. Drug sensitivity varied considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly more resistant to platinum and 5FU and tumor cells from patients previously treated with chemotherapy were generally less sensitive than those from untreated patients. Multivariate analysis showed patient performance status and completeness of CRS to be prognostic for OS. Among patients with complete CRS (n = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin (p ≈ 0.06). At the highest drug concentration tested, the hazard ratio for disease relapse increased stepwise with drug resistance for all drugs.CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic information. The results suggest a role for IPC as therapeutic adjunct to CRS and for individualization of IPC by pretreatment assessment of drug sensitivity.
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- Boyages, John, et al.
(författare)
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Liposuction for Advanced Lymphedema: A Multidisciplinary Approach for Complete Reduction of Arm and Leg Swelling
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 22, s. 1263-1270
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. This research describes and evaluates a liposuction surgery and multidisciplinary rehabilitation approach for advanced lymphedema of the upper and lower extremties. Methods. A prospective clinical study was conducted at an Advanced Lymphedema Assessment Clinic (ALAC) comprised of specialists in plastic surgery, rehabilitation, imaging, oncology, and allied health, at Macquarie University, Australia. Between May 2012 and 31 May 2014, a total of 104 patients attended the ALAC. Eligibility criteria for liposuction included (i) unilateral, non-pitting, International Society of Lymphology stage II/III lymphedema; (ii) limb volume difference greater than 25 %; and (iii) previously ineffective conservative therapies. Of 55 eligible patients, 21 underwent liposuction (15 arm, 6 leg) and had at least 3 months postsurgical follow-up (85.7 % cancer-related lymphedema). Liposuction was performed under general anesthesia using a published technique, and compression garments were applied intraoperatively and advised to be worn continuously thereafter. Limb volume differences, bioimpedance spectroscopy (L-Dex), and symptom and functional measurements (using the Patient-Specific Functional Scale) were taken presurgery and 4 weeks postsurgery, and then at 3, 6, 9, and 12 months postsurgery. Results. Mean presurgical limb volume difference was 45.1 % (arm 44.2 %; leg 47.3 %). This difference reduced to 3.8 % (arm 3.6 %; leg 4.3 %) by 6 months postsurgery, a mean percentage volume reduction of 89.6 % (arm 90.2 %; leg 88.2 %) [p < 0.001]. All patients had improved symptoms and function. Bioimpedance spectroscopy showed reduced but ongoing extracellular fluid, consistent with the underlying lymphatic pathology. Conclusions. Liposuction is a safe and effective option for carefully selected patients with advanced lymphedema. Assessment, treatment, and follow-up by a multidisciplinary team is essential.
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- Crona, Joakim, et al.
(författare)
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Somatic Mutations and Genetic Heterogeneity at the CDKN1B Locus in Small Intestinal Neuroendocrine Tumors
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 22, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Until recently, the genetic landscape of small intestinal neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations, most commonly a loss on chromosome 18. Intertumor heterogeneity with nonconcordant genotype in paired primary and metastatic lesions also is described, further contributing to the difficulty of unraveling the genetic enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B (p27) as a haploinsufficient tumor suppressor gene.METHODS: This study aimed to determine the frequency of CDKN1B inactivation and to investigate genotype-phenotype correlations. It investigated 362 tumors from 200 patients. All samples were resequenced for mutations in CDKN1B using automated Sanger sequencing. The expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors.RESULTS: Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in CDKN1B including 13 insertion deletions, four nonsense variants, and one stop-loss variant. All variants with available nontumoral DNA were classified as somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected respectively in six of ten and two of ten patients. Patients with CDKN1B mutated tumors had both heterogeneous disease presentation and diverse prognosis. Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found.CONCLUSION: This study corroborates the finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene characterized by inter- and intratumor heterogeneity in SI-NETs.
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