ABSTRACT
INTRODUCTION: The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low-grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence. MATERIALS AND SURGICAL TECHNIQUE: Three patients with LAMN previously treated outside our department were selected for second-look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10-mm trocars were inserted-one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m2 and cisplatin 90 mg/m2 for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow-up of 36 months, all patients were asymptomatic with no evidence of recurrence. DISCUSSION: Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach.
Subject(s)
Appendiceal Neoplasms , Laparoscopy , Peritoneal Neoplasms , Appendiceal Neoplasms/therapy , Combined Modality Therapy , Humans , Hyperthermic Intraperitoneal Chemotherapy , Neoplasm Recurrence, Local , Peritoneal Neoplasms/surgery , Retrospective StudiesABSTRACT
BACKGROUND: Lymph node ratio (LNR)-the number of metastatic lymph nodes (LNs) over the number of excised LNs after lymphadenectomy-is a prognostic factor for many solid tumors, but controversies still exist for skin melanoma. We investigated the prognostic relevance of LNR in melanoma patients and formulated a proposal for considering the LNR in the current American Joint Committee on Cancer (AJCC) N staging system. METHODS: Retrospective data of 2,526 melanoma patients with LN metastasis from nine Italian institutions were collected in a multicenter database. The prognostic value of the LNR (categorized as A, ≤0.1; B, 0.11-0.25; and C, >0.25) was assessed by multivariable survival analysis. RESULTS: LNR was a significant independent prognostic factor for melanoma-specific survival (LNR B vs. A: hazard ratio [HR] 1.47, 95 % CI 1.16-1.87, p = 0.002; LNR C vs. A: HR 1.84, 95 % CI 1.29-2.61, p = 0.001). The LNR had prognostic value in patients with AJCC N1a (one positive LN after sentinel LN biopsy [SLNB], HR 2.33, 95 % CI 1.49-3.63, p < 0.001) and N2a (two to three positive LNs after SLNB, HR 1.62, 95 % CI 1.09-2.40, p = 0.016) substages, but not in those with N1b (one clinically positive LN, p = 0.765), N2b (two to three clinically positive LNs, p = 0.165), and N3 (≥ four positive LNs, p = 0.084) substages. CONCLUSION: The LNR is a prognostic factor in melanoma patients with one (AJCC N1a) and two to three (AJCC N2a) positive LNs after SLNB. This easy-to-obtain parameter should be considered for the staging of melanoma patients with LN metastasis, along with the number of positive LNs.
Subject(s)
Lymph Node Excision/mortality , Lymph Nodes/pathology , Melanoma/mortality , Melanoma/pathology , Neoplasm Staging , Adult , Aged , Female , Follow-Up Studies , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Melanoma/surgery , Middle Aged , Prognosis , Retrospective Studies , Skin Neoplasms , Survival Rate , Melanoma, Cutaneous MalignantABSTRACT
The synthesis of a Zn(ii)-phthalocyanine derivative bearing four 10B-enriched o-carboranyl units (10B-ZnB4Pc) and its natural isotopic abundance analogue (ZnB4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented. The photophysical properties of ZnB4Pc, as tested against model biological systems, were found to be similar with those typical of other photodynamically active porphyrin-type photosensitisers, including a singlet oxygen quantum yield of 0.67. The carboranyl-carrying phthalocyanine was efficiently accumulated by B16F1 melanotic melanoma cells in vitro, appeared to be partitioned in at least some subcellular organelles and, upon red light irradiation, induced extensive cell mortality. Moreover, ZnB4Pc, once i.v.-injected to C57BL/6 mice bearing a subcutaneously transplanted pigmented melanoma, photosensitised an important tumour response, provided that the irradiation at 600-700 nm was performed 3 h after the phthalocyanine administration, when appreciable concentrations of ZnB4Pc were still present in the serum. Analogously, irradiation of the 10B-ZnB4Pc-loaded pigmented melanoma with thermal neutrons 24 h after injection led to a 4 day delay in tumour growth as compared with control untreated mice. These results open the possibility to use one chemical compound as both a photosensitising and a radiosensitising agent for the treatment of tumours by the combined application of photodynamic therapy and boron neutron capture therapy.
Subject(s)
Boron Neutron Capture Therapy/methods , Indoles/administration & dosage , Melanoma, Experimental , Organometallic Compounds/administration & dosage , Photochemotherapy , Skin Neoplasms , Animals , Boron/chemistry , Cell Death/drug effects , Cell Death/radiation effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Combined Modality Therapy , Disease Models, Animal , Female , In Vitro Techniques , Indoles/chemical synthesis , Indoles/radiation effects , Isoindoles , Isotopes , Liposomes , Melanoma, Experimental/drug therapy , Melanoma, Experimental/radiotherapy , Mice , Mice, Inbred C57BL , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/radiation effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Skin Neoplasms/drug therapy , Skin Neoplasms/radiotherapy , Structure-Activity Relationship , Time FactorsABSTRACT
The search for new therapeutic approaches to haematological malignant disease involves exploitation of the antitumour potential of adaptive immunity-the most specific killing system against cancer currently known. Here, we summarise immunological strategies behind active specific immunotherapy, and describe the clinical and immunological results from trials published to date. Available data in humans support the hypothesis that various vaccination regimens can polarise adaptive immunity towards effective control of cancer-cell growth. However, the exploratory nature of clinical studies done thus far does not allow any cancer vaccine to be used as standard treatment for haematological malignant disorders. Because the cause of disease recurrence is the presence of minimal residual disease after conventional treatments, the adjuvant setting might be the most appropriate therapeutic strategy for active specific immunotherapy, when the immunosuppressive effects of bulky disease are virtually absent and when the effector-target ratio is favourable. In the near future, completion of randomised phase III trials as well as clinical implementation of the most recent insights into tumour immunology that aim to overcome immune tolerance towards malignant cells should allow investigators to define the actual role of vaccines in the management of haematological tumours.
