Laparoscopic hyperthermic isolated limb perfusion a new minimally invasive approach for HILP.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) represents a limb-sparing treatment for unresectable soft tissue sarcoma (STS) of the extremities with substantial complete response rates. HILP often provides good functional limb preservation, hence a significant improvement also in terms of quality of life of the patient. Notwithstanding these clear advantages, the traditional technique is still hindered by relatively high post-operative morbidity. METHOD: We treated a 78-year-old female with unresectable angiosarcoma of the left leg using a new surgical approach: an entirely laparoscopic HILP. RESULTS: No conversion from laparoscopic to "open" surgery was necessary. Since no abdominal muscle section was performed, post-operative pain was low and easily manageable; early mobilisation and early discharge were achieved. Patient developed moderate toxicity, which resolved spontaneously within 3-4 weeks, with complete return to normal daily activities after 30 d. Complete clinical response with preservation of leg function was obtained. CONCLUSIONS: We describe for the first time an entirely laparoscopic HILP. Demonstration of this technique's efficacy and safety on a large series of patients is clearly necessary but its therapeutic efficacy appears to be comparable to the standard technique. Furthermore, laparoscopic HILP has shown low post-operative morbidity: no wound complications, mild and easily manageable post-operative pain and early discharge from the hospital and early resuming of daily activities.

A two-step selection of breast cancer patients candidates for exclusive IORT with electrons: a mono-institutional experience.

AIM: To assess the impact of a two-step multiparameter selection on the actual enrollment of women with breast cancer into a prospective intraoperative radiotherapy (IORT) trial. PATIENTS AND METHODS: From September 2009, a prospective clinical trial was started in order to deliver adjuvant exclusive single -fraction IORT to patients with early breast cancer. To select patients meeting suitable eligibility criteria for the clinical trial, a two-step decision process was developed: at pre-surgical examination (first step) and during surgery (second step). RESULTS: A series of 464 patients with breast cancer was analysed: at the first step, out of 464 patients, 333 (71%) were considered eligible for the IORT protocol; at the second step, out of 333 patients, 199 (60%) met the eligibility criteria and received the IORT fraction according to the criteria of the controlled trial. CONCLUSION: In our experience, the ultimate rate of patients who enrolled in the IORT clinical trial after the two-step decision process was 43%.

Regeneration of mandibular osteoradionecrosis defect with platelet rich plasma gel.

Osteoradionecrosis (ORN) of the mandible is a major complication of radiation therapy of head and neck cancer with a potential of occurrence ranging from 5 to 15% of the irradiated patients. Due to the gradual necrotic process, the mandibular bone becomes necrotic and looses its spontaneous regeneration ability. Containing an elevated content of mitogenic and osteogenic growth factors, the use of platelet rich plasma (PRP) from autologous source has been suggested to re-activate the healing process of osteogenesis. Autologous PRP gel was introduced into the ORN necrotic defect of a 44-year old patient previously treated for squamous cell carcinoma of the tongue, subsequent to proper surgical debridement. We report post-operative two-year follow-up demonstrated by panoramic X-ray which showed regain of the mandibular bone continuity with a complete repair of the necrotic defects. We conclude that this case illustrates an incident of successful regeneration of ORN critical-sized defect of the mandible by autologous PRP gel.

Kinetics of galactomannan in surgical patients receiving perioperative piperacillin/tazobactam prophylaxis.

OBJECTIVES: The association between piperacillin/tazobactam and the positivity of the galactomannan (GM) detection ELISA test is well described. Little information is available about the kinetics of GM in patients treated with piperacillin/tazobactam. The present study aimed at clarifying the baseline interaction between piperacillin/tazobactam and GM in patients receiving this drug. PATIENTS AND METHODS: Seven patients undergoing abdominal surgery received perioperative prophylaxis with piperacillin/tazobactam. Each patient received three doses of 4.5 g of the drug, administered at 8 h intervals (one before and two after surgery). Three patients received antibiotic batches with 'medium' (GM-index = 1.782) and four patients received antibiotic batches with 'high' (GM-index = 6.665) GM content. Serum samples for GM evaluation were collected before drug infusion and at times +1, +3, +6 and +8 h after the first and third infusions. RESULTS: GM levels increased after infusion, in particular when batches with 'high' GM content were used. Moreover, a non-statistically significant increase between the first dose and the third dose was observed. All samples taken >6 h after administration were negative (GM-index < 0.2), both with the 'medium' and the 'high' GM content batches. CONCLUSIONS: The low content of GM 8 h after piperacillin/tazobactam infusion suggests that in non-neutropenic cancer patients with solid tumours receiving up to three doses of piperacillin/tazobactam, serum sampling for GM detection should be performed immediately before the next piperacillin/tazobactam administration.

The role of axillary lymph node dissection in breast cancer patients with sentinel lymph node micrometastases.

AIM: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND). MATERIALS AND METHODS: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN. RESULTS: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring

The prognostic role of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma: experience of the Genoa group.

AIM: To define the benefit of intraoperative frozen section examination of the sentinel lymph node (sN), and to assess its prognostic value in clinically node-negative melanoma patients. MATERIALS AND METHODS: Between July 1993 and December 2001, 214 patients with Stage I-II cutaneous melanoma underwent sN biopsy; complete follow-up data are available in 169 of 175 patients who underwent preoperative lymphoscintigraphy, lymphatic mapping with Patent Blue-V and radio-guided surgery (RGS). RESULTS: In an initial subset, the sN was identified in 35 out of 39 patients; in the principal group of 169 patients, the sN was detected in all patients. The benefit of frozen section examination, that is the proportion of all patients having intraoperative histologic examination who tested positive, was 17.2% (29/169); notably, in patients with pT(1-2) vs pT(3-4) melanoma the corresponding values were 2.3 and 33.3%, respectively, (P=0.000). Cox regression analysis for overall survival indicated that sN-positive patients had a two-fold increased risk of death; the most significant predictors of relapse-free survival were sN status (P=0.004), age (P=0.015), and T stage grouping (P=0.033). CONCLUSIONS: The sN is a reliable predictor of regional lymph node status in patients with cutaneous melanoma. Frozen section examination can be useful in avoiding a 'two-stage' operative procedure in patients with tumour-positive sN, but its greatest benefit seems to be restricted to patients with pT(3)-pT(4) primary melanoma.

Solitary fibrous tumor of the inguinal region: a clinicopathological, light-microscopic, immunohistochemical, electron microscopic and flow-cytometric DNA study.

Solitary fibrous tumors (SFTs) are rare neoplasms with a probable mesenchymal origin that were first reported in the pleura but can occur in different sites. We report a case of SFT arising in the inguinal region of a 55-year-old woman. The patient presented with a mass in the left groin; she underwent wide excision of the lesion which was well-circumscribed and without evidence of adjacent soft tissue involvement. The histological, immunohistochemical and electron microscopic criteria for SFT were found. She had an uneventful recovery and she is alive without evidence of disease five years after operation. To our knowledge, this neoplasm has never been reported in this location.

Preliminary analysis of a randomized clinical trial of adjuvant postoperative RT vs. postoperative RT plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer.

OBJECTIVES: Two-hundred eighteen patients with TNM stage II-III resectable rectal cancer, enrolled into a randomized clinical trial, were assessed for efficacy and toxicity of adjuvant postoperative radiation therapy (RT) vs. those of combined RT and chemotherapy (CT), with 5-fluorouracil (5-FU) plus levamisole. End points were overall survival, disease-free survival, the rate of loco-regional recurrence, and treatment-related toxicity. METHODS: Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/m(2)/day intravenous bolus, days 1-5) plus levamisole (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and levamisole every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were normal. RESULTS: RT was completed or modified in 170 (90%) of 189 evaluable patients undergoing RT (both treatment groups). Only 44 (59%) of 75 evaluable patients of arm II completed or had an adjustment of the CT schedule; the remaining 31 patients (41%) had to stop or never started the CT regimen. Patients undergoing combined RT and CT had more severe toxicity (enteritis, P = 0.03). There was one CT-related death (gastrointestinal bleeding) in this subset. No significant difference was observed in outcome of patients in the two study groups, nor for pattern of recurrence (heterogeneity chi(2) = 4.82; d.f. = 2; P = 0.08). CONCLUSIONS: These preliminary findings suggest a similar efficacy, coupled with less morbidity, of postoperative RT alone compared with a combined regimen of postoperative RT and CT in patients undergoing radical surgery for stage II-III rectal cancer.

Mapping the sentinel lymph node in malignant melanoma by blue dye, lymphoscintigraphy and intraoperative gamma probe.

Eighty-eight consecutive patients (48 men and 40 women; mean age, 58.9 years; range, 16-84 years) with clinically localized cutaneous melanoma involving the trunk, extremities or head and neck underwent lymphatic mapping at our institution. The primary melanoma had a mean thickness of 2.74 mm (range, 0.95 to 9 mm). Patients were divided into two groups: group A (39 patients) underwent only vital blue dye (VBD) mapping, while group B (49 patients) underwent lymphatic mapping with VBD and radio-guided surgery (RGS) combined. In all patients 1-1.5 mL of VBD was injected subdermally around the biopsy scar 10-20 min before surgery. In group B 37 MBq in 150 microL of 99mTc-HSA nanocolloid was additionally injected intradermally 18 h before surgery (3-6 aliquots injected perilesionally). In all lymphatic basins where drainage was noted the sentinel lymph nodes (SNs) were identified and marked with a cutaneous marker. Final identification of the SN was then performed externally by a hand-held gamma probe. After the induction of anesthesia 0.5-1-0 mL of patent blue V dye was injected intradermally with a 25-gauge needle around the site of the primary melanoma. SNs were examined by routine hematoxylin and eosin (H&E) staining and immunohistochemistry. Patients with histologically positive SN(s) underwent standard lymph node dissection (SLND) in the involved lymph node basin. The SN was identified in 37/39 patients (94.9%) of group A and in 48/49 patients (98.0%) of group B. Blue dye mapping failed to identify the SN in 5 of the 88 patients (5.8%), while the radioisotope method failed in only 1 of 49 patients (2.0%). Similar results were obtained with the combined use of the two probes. The average number of SNs harvested was 1.9 per basin sampled, which does not differ significantly from the numbers reported by other authors. The SN was histologically positive in 18 patients (20.5%). None of the 12 patients with a Breslow thickness less than 1.5 mm had positive SNs, whereas 18 of the 77 patients (23.4%) with a Breslow index exceeding 1.5 mm showed metastatic SNs with H&E or immunohistochemistry. The latter all underwent SLND of the affected basin. In 10 patients (55.6%) the SN was the only site of tumor invasion; eight patients (44.4%) with positive SNs had one or more metastatic lymph nodes in the draining basin.

Selective lymph node dissection in patients with intermediate thickness melanoma: our experience.

The role of elective lymph node dissection (ELND) for the treatment of cutaneous melanoma has been debated for many years. Actually, the value of ELND is seriously questioned because an increasing of overall survival rates has not been demonstrated. The lymphatic mapping technique, initially performed by an intradermic injection of vital blue dye, subsequently improved by the use of radioguided surgery (RGS), proved effective for the detection of clinical occult lymph node metastasis. We performed a sentinel node biopsy on 71 patients with stage pT2/T3N0M0 melanoma. Vital blue dye mapping alone was performed on 39 patients; the remaining 32 patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel node (SN) was complexively identified in 69/71 (97.2%) patients. Sixteen patients (23.2%) were found to have metastatic melanoma cells in their SN(s); all these patients underwent lymph node dissection of the affected basin. Our experience confirmed that the intraoperative detection of sentinel nodes using both blue dye and radio-guided surgery is an effective and reliable technique for selecting patients to be submitted to lymph node dissection.

Malignant melanoma of soft tissues (clear cell sarcoma) of the foot. Is MRI able to perform a specific diagnosis? Report of one case and review of the radiological literature.

The magnetic resonance (MR) findings in malignant melanoma of soft tissues, also called clear cell sarcoma of tendons and aponeuroses, have been described as a focal abnormality with a specific MR pattern of increased signal intensity (relative to normal muscle) on T1 weighted sequences and variably decreased signal intensity on T2 weighted sequences (relative to surrounding fat). We have reported here a case of malignant melanoma of soft tissues of the foot, studied with ultrasonography (US) and MR, in which MR showed T1-hypointensity, T2-hyperintensity and marked gadolinium uptake. We have described the relationship between the intracytoplasmic melanin amount of and these atypical MR findings.

Intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) co-expression in cutaneous malignant melanoma lesions.

The expression of intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) was investigated in 25 melanoma patients by evaluating 34 fresh biopsy specimens. ICAM-1 in situ hybridization and immunochemistry for ICAM-1 and GM-CSF were performed. Most of the metastatic melanoma samples (12 out of 18) and a few of the primary melanoma lesions (three out of 16) showed ICAM-1 expression. The expression of ICAM-1 was significantly (P < 0.01) higher in metastatic lesions than in primary tumours. GM-CSF mRNA and protein were detected in 10 of the 18 metastatic samples and in two of the 15 primary lesions. A significantly high degree (P < 0.0002) of concordance between ICAM-1 and GM-CSF expression was observed: the samples that were negative or positive for ICAM-1 expression were correspondingly negative or positive for GM-CSF. Correlation with clinical and histological parameters was examined. The expression of both molecules in metastatic samples was found to be significantly (P < 0.001) associated with a shorter recurrence-free period. These findings, if confirmed by a wider number of patients, could suggest the prognostic value of the simultaneous, and probably co-ordinated, expression of ICAM-1 and GM-CSF. They also highlight the importance of preventive molecular and biochemical characterization of neoplastic cell cytokine receptors, specifically focusing on the particular cytokine to be used as anticancer therapy and/or as adjunct to chemotherapy.

Adoptive immunotherapy with tumor-infiltrating lymphocytes and subcutaneous recombinant interleukin-2 plus interferon alfa-2a for melanoma patients with nonresectable distant disease: a phase I/II pilot trial. Melanoma Istituto Scientifico Tumori Group.

BACKGROUND: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-alpha2a), for patients with metastatic melanoma. METHODS: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m2/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-alpha2a was administered subcutaneously at 3 X 10(6) IU three times each week until progression. RESULTS: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 x 10(9) (range, 1-43 x 10(9)), and the median period of culture was 52 days (range, 45-60). rIL-2 was administered at doses ranging between 6 and 18 x 10(6) IU/m2/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2-35%). CONCLUSIONS: Outpatient treatment with TIL plus rIL-2 and rIFN-alpha2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.

Radioimmunoguided surgery benefits in carcinoembryonic antigen-directed second-look surgery in the asymptomatic patient after curative resection of colorectal cancer.

Radioimmunoguided surgery (RIGS) with radiolabeled monoclonal antibodies (MoAbs) has been reported as useful in second-look colorectal cancer procedures to improve surgical decision-making by helping avoid needless extensive surgery and expanding curative resection to sites of recurrence that have been missed previously. Sixteen asymptomatic patients with an history of colorectal cancer surgery underwent second-look surgery using the RIGS system, solely on the basis of rising serum levels of carcinoembryonic antigen (CEA). All patients were injected preoperatively with the anti-tumor-associated glycoprotein (TAG) 125I-labeled MoAb B72.3. Both traditional and RIGS exploration were used to determine the extension of a possible recurrence and its resectability for cure. Recurrent disease was observed in 14 of the 16 patients as the result of this combined exploration. Exploration alone showed the presence of recurrent disease in 9 of 16 patients (56.2%). Thus, RIGS found overlooked tumor in five patients (31.2%). All the additional RIGS-detected tumor sites were locoregional recurrences resectable for cure; conversely, no diagnostic improvements were shown in patients with liver metastases. Resection for cure was obtained by this approach in 9 of 16 patients (56.2%). Two patients without disease at the exploratory laparotomy recurred within 2 months at sites away from the abdomen. RIGS improved the results of colorectal cancer CEA-guided second-look procedures in asymptomatic patients by recruiting one-third of patients to curative resections.

Sentinel lymph node mapping opens a new perspective in the surgical management of early-stage breast cancer: a combined approach with vital blue dye lymphatic mapping and radioguided surgery.

Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. However, some important issues need further definition: (1) optimization of the technique for intraoperative detection of the sN; (2) predictive value of the sN as regards axillary lymph node status, and (3) reliability of intraoperative histology of the sN. We report our experience in sN mapping in patients with Stage I-II breast cancer, with the aim of assessing: (1) the feasibility of lymphatic mapping with a combined approach (vital blue dye lymphatic mapping and radioguided surgery); (2) the agreement of the intraoperative histologic examination of the sN, by means of hematoxylin and eosin staining with final histology, and (3) the accuracy of sN histology as a predictor of axillary lymph node status.

Sentinel node biopsy in patients with cutaneous melanoma.

The role of elective lymph node dissection (ELND) for treatment of cutaneous melanoma is still debated. Initially, lymphatic mapping technique was performed by an intradermic injection of vital blue dye; subsequently, it was improved by the use of radioguided surgery (RGS). Preliminary experience with this technique proved effective for detection of clinical occult lymph node metastasis; it may also enable the surgeon to perform a selective lymph node dissection (SLND) to concentrate on pathologic node-positive patients for the same potential benefits that have been provided by ELND. We performed sentinel node biopsy on 48 patients with stage pT3N0M0 melanoma. Vital blue dye mapping only was carried out on 39 patients; the remaining nine patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel lymph node (SLN) was identified in 46 of 48 patients (95.8%). Ten patients (20.8%) were found to have metastatic melanoma cells in their SLN(s); all these patients underwent SLND of the affected basin. Our findings confirm that the intraoperative lymphatic mapping of the SLN using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.