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.

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

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

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.

Prophylaxis of infection with intravenous immunoglobulins plus antibiotic for patients at risk for sepsis undergoing surgery for colorectal cancer: results of a randomized, multicenter clinical trial.

BACKGROUND: The results of a randomized, multicenter clinical trial with perioperative short-term antibiotic plus intravenous immunoglobulins (IVIG + A) versus antibiotic alone (A) for prevention of postoperative infections in patients at risk for sepsis undergoing surgery for colorectal cancer are presented. METHODS: The patients at risk for sepsis were selected by an original multiparametric test based on delayed-hypersensitivity skin testing and serum protein electrophoretic subfractions. This screening had shown 76% positive predictability in a previous validation assessment. Eighty patients at risk for sepsis were selected prospectively from 210 patients undergoing surgery for colorectal cancer; 43 patients were randomly assigned to the IVIG + A group and 37 to the A group. IVIG was administered on the day before operation, on the first and fifth postoperative days. RESULTS: There was a clear-cut reduction of postoperative infections in the IVIG + A group: 21 infections in 20 patients versus 37 infections in 29 patients in the A group (p less than 0.004). With regard to serum immunoglobulin (Ig) G monitoring, basal IgG levels were significantly lower in patients given IVIG + A who had postsurgical infections (p less than 0.005) compared with patients with a regular outcome, whereas the same was not true in the A group of patients. CONCLUSIONS: A significant decrease (p less than 0.001) of postoperative IgG was evidenced in the A group of patients who had infections as opposed to a significant increase (p less than 0.001) of postoperative IgG in IVIG + A patients with a normal outcome.

Analysis of the proliferative and phenotypic properties of tumor infiltrating lymphocytes expanded in vitro in the course of the clinical trial of adoptive immunotherapy of metastatic melanoma.

Adoptive immunotherapy with in vitro expanded tumor infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) is a recent option in the treatment of advanced melanoma resistant to conventional chemotherapy. In the course of a protocol of treatment of advanced melanoma with in vitro expanded TIL and rIL-2, we obtained 38 samples from 27 different patients. Lymphocytes derived were cultured in the presence of rIL-2 in vitro for a 4-6 week period and 23 resulted in proliferative cultures. Eighteen samples were infused in the course of the clinical trial. The median number of lymphocytes obtained was 18x10(9) (range 1-43x10(9)) cells. Phenotypic analysis showed that all samples contained a pure population of T cells. These data confirm that lymphocytes can be expanded from advanced metastatic sites, have peculiar characteristics and are suitable to be infused in vivo.

Regional arterial chemotherapy of liver tumours. I. Performance comparison between a totally implantable pump and a conventional access system.

Thirty-nine patients with liver tumours have been submitted to regional arterial chemotherapy by means of either totally implantable Infusaid-400 pumps (22 c.) or implantable ports (17 c.). The latter were subsequently perfused with external pumps. There was one single major operative complication and no operative deaths. Most patients underwent continuous Fudr infusion. Access related complications occurred in both groups. Treatment was stopped for access related complications in 18.4% and 29.4% of cases out of the pump and port groups respectively. In most of those cases, however, several cycles of chemotherapy had already been performed. The Infusaid-400 pumps showed a 12-month functional duration of 57% with a 13-month median, the 10-month duration of ports being 67%. The difference was not significant. The new implantable systems give better results in comparison with traditional regional access methods, the functional performances of the port systems appearing very similar to the totally implantable pumps, with an obvious advantage for the pumps as far as quality of life is concerned.

Selection of pre-operative haematobiochemical parameters for the identification of patients 'at risk of infection' undergoing surgery for gastro-intestinal cancer.

Sixty-three patients were given a complete laboratory screening before undergoing surgical treatment for cancer of the digestive tract. The values of all these parameters were correlated with the incidence of postoperative infections, with the aim of identifying those markers which could be useful for the pre-operative selection of the patients at risk of infection. Patients who developed postoperative infections showed a significant pre-operative reduction of total serum proteins (P less than 0.02), albumins (P less than 0.02), beta-globulins (P less than 0.01) and C3c (P less than 0.05), while alpha 1-globulins were slightly, but not significantly, increased. The possible clinical applications of these parameters, to develop a predictive model which may help identify the patients at risk of infection, are discussed.

Long-term femoral vein central venous access in cancer patients.

Subclavian percutaneous access with reservoir placement has been shown to be difficult or contraindicated in some patients. Of 465 cancer patients who required a port placement between January 1992 to January 1995, 41 (8.8%) had alternative percutaneous femoral access with a totally implantable port reservoir located in the abdomen because of the inaccessibility to subclavian or jugular veins and/or the presence of massive cutaneous metastases or severe radiodermitis in the upper part of the torso. Overall implant days was 9880, with an average of 241 days (range: 65-445). Ports were alternatively used for chemotherapy and nutritional purposes in 11 of 41 patients. Late morbidity causing the removal of the implanted ports was observed in two of 41 (4.9%) and 25 of 424 (5.9%) patients in the femoral and subclavian series, respectively (P = 0.86). The femoral percutaneous access for totally implantable port devices appears to be a safe alternative for cancer patients when subclavian and/or jugular vein catheterization and reservoir in the upper part of the torso is contraindicated.

Long-term postoperative results in 54 cases of early gastric cancer: the choice of surgical procedure.

Surgical experience on the management of early gastric carcinoma (EGC) related to a series of 54 subjects was observed from 1974 to 1984. Thirty-four patients were male, 20 were female; median age was 61.84 (range 22-79) years. Malignancy always occurred in the middle or distal third of the stomach. A partial subtotal gastrectomy (two-thirds of the stomach) with Roux en Y or Billroth II reconstruction was performed. Omentectomy and lymph node dissection of the primary and secondary groups of nodes, according to General Rules, was always performed. Age-corrected 5- and 10-year survival rates were 95.7% and 84.3%, respectively. Based on their experience, the authors discuss the surgical approach to EGC stressing the need for an accurate lymph node dissection and pointing out that results of subtotal gastrectomy are similar to that reported in the literature for total gastrectomy. The only absolute need for a total gastrectomy may be the presence of an EGC in the proximal third of the stomach. To this end the authors compare their results with 5- and 10-year series from Japanese and western countries reported in the literature.

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.

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.

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.

Pseudomixoma peritonei: a case report.

Pseudomixoma peritonei is a rare neoplasm characterized by mucinous ascites and the mucinous involvement of peritoneal surfaces, omentum and bowel loops. Usually pseudomixoma peritonei is associated with benign or malignant mucinous tumor of the appendix or ovary. The diagnosis of pseudomixoma peritonei is difficult because laboratory and radiology results are frequently nondiagnostic. We report a case that was initially mistaken for carcinomatosis of unknown origin and that underwent cytoreductive procedure and omentectomy as the treatment of choice.

Merkel cell carcinoma of the skin. Treatment of primary, recurrent and metastatic disease: review of clinical cases.

The clinical features of 10 cases of primary neuroendocrine carcinoma of the skin (Merker cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissues of elderly individuals. Natural history is characterized by local recurrences (30%), regional lymph node metastases (65%) and distant metastases (40%). Surgery is elective treatment, chemotherapy and radiotherapy resulted only to short-term palliative response.

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.

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.

[Case of hemorrhagic pericarditis as the initial manifestation of pulmonary adenocarcinoma]. / Un caso di pericardite emorragica come prima manifestazione di un adenocarcinoma polmonare.

The Authors describe a case of pericardial involvement as the first sign of lung adenocarcinoma. Several evacuatory pericardiocentesis were required to treat recurrent hemorrhagic effusion. Pericardiectomy was finally carried out. The course of pericarditis was rapid: three and half months elapsed from the first symptoms of dyspnea to the death of patient.