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.

Anti-tumoral effects of somatostatin analogs: a lesson from the CLARINET study.

Octreotide and lanreotide, the first-generation somatostatin analogs, successfully control hormone hyperproduction, and related syndromes, in patients with acromegaly and neuroendocrine tumors. However, their anti-tumor effect, rather evident in large number of pituitary adenomas in acromegalic patients, has been hypothesized for a long time in patients with neuroendocrine tumors as well, although a significant tumor shrinkage has rarely been observed. However, the recent publication of the CLARINET study has strengthened the evidence, already emerged with the PROMID trial, that the long-term treatment with the first-generation long-acting somatostatin analogs may exert an anti-tumor activity on G1 and G2 enteropancreatic neuroendocrine tumors, as well. After the publication, majority of international guidelines have updated their algorithms in line with these results and this class of drugs obtained the indication as anti-tumor agents in the majority of patients with neuroendocrine tumors.

Surgical prevention and treatment of lymphedema after lymph node dissection in patients with cutaneous melanoma.

Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.

Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.

[Cryosurgery with transpleurodiaphragmatic approach in the treatment of non-resectable and recurrent hepatic metastasis from the colorectum]. / La criochirurgia con accesso transpleurodiaframmatico nel trattamento delle metastasi epatiche colorettali non resecabili e recidive.

Cryotherapy allows the destruction of unresectable liver malignancies. The abdominal approach is uneasy for recurrent colorectal metastases located in the upper part of the liver and close to the inferior vena cava, the hepatic veins and the diaphragm. A transpleurodiaphragmatic access was employed. From 1999 to 2003, ten patients with recurrent colorectal liver metastases underwent transdiaphragmatic cryotherapy via a right thoracotomy. Median diameter was 30 mm. One to 4 cryoprobes were used, depending on the size and location of the metastasis. There were no operative deaths, and only 3 patients developed minor complications. Computerized tomography examination of the liver performed one week, three months after cryotherapy, assessed treatment completeness in all patients. At 14 months, 9 patients were alive and 6 were disease-free. Two patients had liver recurrences outside the cryolesion. A transthoracic access may represent the safest and easiest surgical approach for liver tumor cryoablation in selected patients with non resectable recurrent metastases of the upper liver.

Intraperitoneal mitoxantrone: a feasibility and pharmacokinetic study.

Fractionated doses have been advocated to prevent chemoperitonitis after intraperitoneal infusion of mitoxantrone. Patients with peritoneal carcinomatosis of various origin underwent surgery, including intestinal resections, with minimal residual disease. Peritoneal mitoxantrone in 1000 ml/m(2) saline was planned on the first post-operative day in groups of four patients (5 mg/m(2) for 3 and 5 days, 7.5 mg/m(2) for 3 and 4 days, 10 mg/m(2) for 2-4 days, if possible). Due to dose-limiting myelosuppression, only one and three patients received the 7.5-mg 4-day and 10-mg 3-day regimens, respectively. A total of 20 patients were consequently treated. Neither major complications nor severe pain were observed. Pharmacokinetics were completed on the 1st day in five 5-mg and five 10-mg patients, on the 5th day in three 5-mg patients, and on the 3rd day in one 10-mg patient. On the 1st day, mean peritoneal peak concentrations of mitoxantrone resulted 1.45 +/-0.56 (range 0.48-1.9) and 1.9+/-0.85 (range 1.27-3.13) microg/ml in the 5-mg and 10-mg patients, respectively. Mean dialysate/plasma exposure (AUC) ratio was 115. Even in patients with sutures, early post-operative fractionated intraperitoneal mitoxantrone appears feasible and safe, with a high local advantage, for up to 5 days of treatment and a maximum tolerated total dose of 20-25 mg/m(2).

Multimodality treatment of patients with liver metastases from germ cell tumors: the role of surgery.

BACKGROUND: The presence of liver metastases represents an independent poor risk prognostic factor for survival in patients with germ cell tumors. METHODS: The clinical files of 37 patients who had undergone liver resection for the treatment of disseminated germ cell tumors were reviewed to define the indications for resection of residual liver metastases after chemotherapy in patients with germ cell tumors. The histologic patterns of primary tumor and residual disease were compared. The prognostic factors for survival were studied by univariate analysis. RESULTS: All but 2 of 37 patients underwent complete resection. One patient died of postoperative complications. Thirteen complications occurred in 10 patients. Twelve patients had active residual tumor, 7 patients had mature teratoma, and 18 patients had only necrosis on histologic examination. Twenty-three of 37 patients (62%) were alive with no evidence of disease after a median follow-up of 66 months (range, 31-134 months). Three prognostic factors were found to be significant in the univariate analysis for unfavorable outcome: the presence of pure embryonal carcinoma in the primary tumor, liver metastases measuring > 30 mm in greatest dimension at the time of surgery, and the presence of viable, active residual disease. CONCLUSIONS: Because it is impossible to determine the histologic pattern of residual liver masses after chemotherapy with current imaging tools and percutaneous biopsy, patient selection for liver surgery may be undertaken according to the size of residual liver masses. Patients with masses that measure < or = 10 mm in greatest dimension should be considered for close follow-up, because they have a high probability of necrosis and are at low risk for malignant disease. Male patients with masses that measure > or = 30 mm in greatest dimension represent a high-risk group of patients who are not likely to benefit from liver surgery. Only male patients with masses that measure 10-29 mm in greatest dimension and all female patients with masses that measure > 10 mm in greatest dimension should be considered for liver resection.

Cryosurgery as a means to improve surgical treatment of patients with multiple unresectable liver metastases.

BACKGROUND: The aim of the study was to evaluate the results of cryosurgery in patients with multiple (five or more), heavily pretreated, unresectable liver metastases. MATERIALS AND METHODS: Nineteen patients with multiple unresectable liver metastases were entered into a prospective nonrandomized trial. The liver tumours were treated during surgery under ultrasound guidance. All the patients were followed-up to assess complications, treatment response and sites of recurrence. RESULTS: 140 metastases were identified in 19 patients (mean, 7; range, 5-25) and 13 patients had a synchronous liver resection. Cryosurgery was used to treat 90 metastases (mean diameter, 30 mm; range, 10-135). There were no treatment-related deaths and the overall rate of complications was 21%. During a mean follow-up of 28 months (range, 5-60), tumours recurred at the site of cryosurgery in two patients (10%), in the remaining liver in nine patients (47%) and elsewhere in five patients (26%). Three patients had no evidence of disease 48, 50 and 60 months after liver cryosurgery, respectively. CONCLUSION: Cryosurgery may be effective in the treatment of patients with multiple unresectable liver metastases and should be investigated in multimodality treatment programmes.

Desmoid tumor arising in a cesarean section scar during pregnancy: monitoring and management.

Desmoid tumors (DTs) are frequently associated with either surgical trauma, like scars, or physiologic trauma, like pregnancy. A DT arising in a cesarean scar during pregnancy shows both correlations. A case of DT that grew gradually in a cesarean scar during the first trimester of a subsequent pregnancy is presented. After initial MR imaging, the lesion was biopsied and carefully monitored; immediate surgical removal was considered at any time if indicated by the follow-up results. No increase in the tumor size was observed during the following 6 months of gestation, and the lesion was extirpated with mesh replacement of the abdominal defect at the time of cesarean section.

Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior. METHODS: This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia. RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. CONCLUSION: This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

[Pancreatic cancer. Analysis of 149 cases in our 17-year experience]. / Il carcinoma del pancreas. Analisi di 149 casi in 17 anni di esperienza.

The Authors analyse a series of 149 consecutive patients with carcinoma of the pancreas or the periampullary region. Curative surgical treatment was achievable in 55 patients, palliative procedures included surgery in 68 patients; biliary decompression with endoscopic or percutaneous procedure in 25 patients and chemotherapy in one patient with lymphoma. Perioperative complications consisted in gastroplegia (33%), pancreatic fistula (22%), biliary fistula (7.3%), abdominal abscess (5.5%) and hemoperitoneum (1.8%). Five patients died within 30 days after surgery (9%). The overall median postoperative survival was 37, 29 and 21 months in papillary, choledochal and pancreatic cancer, respectively.

Differential device performances for hepatic arterial chemotherapy: a technical report on totally implantable pumps and ports for both continuous and bolus infusion.

Performances of totally implantable infusion systems were analyzed in patients with colorectal liver metastases undergoing intra-arterial treatment. It consisted of 14-day continuous infusion of 5-fluor-2'deoxyuridine with pumps (pump14, 44 patients) or ports fed by external pumps (port14, 34 patients), or bolus infusion of cisplatin (port21, 57 patients) or epirubicin (port7, 22 patients) every 3rd week and weekly, respectively. Toxicity and disease progression were the most common causes of treatment interruption. System failure occurred in 2 pump14, 9 port14, 6 port21 and 2 port7 cases. Pocket problems were most frequent in the pump14 group (30%), whereas catheter- and infusion-related problems were mostly observed in the port14 group (109%). The devices were still functional after 12 months in 92% of pump14, 24% of port14, 65% of port21 and in 78% of port7 patients. Although implantable ports allow adequate infusion periods, in most cases they appear especially suitable for bolus infusions.

Hernia repair in elderly patients.

BACKGROUND: This study evaluates a 5-year experience of the management of the most frequent abdominal wall hernias in an elderly population. METHODS: From April 1990 to December 1995, 231 inguinal, 12 femoral and seven umbilical hernias were repaired in 221 patients (mean age 74 (range 66-93) years). Concomitant diseases were present in 157 patients. A mesh repair was performed with 'tension-free' or 'plug' techniques in all but 23 inguinal and two femoral hernia repairs, in which the Bassini or Shouldice procedures were adopted. Ten emergency hernia repairs were performed for strangulation. A total of 232 operations, including four emergency hernia repairs, were carried out under local anaesthesia. RESULTS: There was no perioperative mortality. Acute intestinal bleeding occurred 2 days after surgery in a patient with colonic diverticular disease. Urinary retention occurred once following emergency hernia repair under general anaesthesia and twice after elective hernia repair under local anaesthesia. Local complications included four scrotal haematomas (2 per cent), three wound infections (1 per cent) and one case of orchitis with atrophy after repair of a recurrent hernia. There was one recurrence after a Bassini repair and one after Shouldice inguinal herniorrhaphy. No recurrence was observed after mesh repair. CONCLUSION: Local anaesthetic mesh hernia repair is safe and effective in elderly patients. Age should be no bar to elective hernia repair. This policy should avoid the complications of emergency operation.

[Lipiodol with and without Gelfoam in primary liver tumors. Plasma levels of Mitoxantrone and clinical results]. / Lipiodolizzazione associata o meno a Gelfoam in pazienti con tumore epatico primitivo. Livelli plasmatici di Mitoxantrone e risultati clinici.

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.

[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans]. / Effetto della ialuronidasi adiuvante in tumori refrattari alla chemioterapla. Revisione della letteratura e farmacocinetica del cisplatino dopo somministrazione regionale nell'animale e nell'uomo.

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.

[Performance and complications of totally implantable port device in bolus hepatic intra-arterial chemotherapy]. / Funzionalità e complicanze dei "port" totalmente impiantabili per la chemioterapia intraarteriosa epatica in bolo.

The performances of totally implantable ports were analyzed in patients with colorectal metastases undergoing intraarterial treatment. Seventy-nine patients received bolus infusion of Cisplatin (DDP, 57 cases) or Epirubicin (EPI, 22 cases) every 21 and 7 days, respectively. Disease progression or toxicity were the most common causes of interruption of treatment, whereas failure of ports occurred in six and two patients out of DDP and EPI groups, respectively. The incidence of single problems for each port was 65% in DDP group and 64% in EPI group, whereas rate of complications for each patient was 30% and 32%, respectively. The 12-months device duration rate in the two groups was 65% (median 17 months) in DDP group and 78% (median 18 months) in EPI group. The implantable ports employed for bolus arterial infusion, allowed adequate treatment periods in most cases, without any difference as far as intervals between cycles is concerned.

Autoimmunity in myocarditis and dilated cardiomyopathy: cardiac autoantibody frequency and clinical correlates in a patient series from Italy.

BACKGROUND: Organ- and disease-specific cardiac autoantibodies, detected by indirect immunofluorescence, represent markers of autoimmunity in a subgroup (25-35%) of patients with dilated cardiomyopathy or myocarditis from Northern Europe and the United States of America. Autoantibody frequencies, as well as associations between clinical and immunological features, may vary in patients from different countries, due to ethnically related differences in genetic susceptibility to autoimmune disease. METHODS: We assessed the frequency of cardiac autoantibodies in a series from Italy, including 91 subjects with idiopathic dilated cardiomyopathy (61 male, aged 49 +/- 11 years) and 11 with biopsy-proven (Dallas criteria) myocarditis (7 male, aged 23 +/- 16), including 2 cases of giant cell myocarditis. Controls were 160 patients with other cardiac disease, 141 with ischemic heart failure and 270 normals Cardiac antibody test was performed blindly by indirect immunofluorescence on normal human myocardium and skeletal muscle. RESULTS: The frequency of organ-specific cardiac autoantibodies was higher (p = 0.0001) in myocarditis (45%) and in dilated cardiomyopathy (20%) than in other cardiac disease (1%), in ischemic heart failure (1%), or in normals (2.5%). Cross-reactive antibodies were detected in similar proportions of study patients and controls. Both patients with giant cell myocarditis were antibody positive. Myocarditis patients with cardiac antibodies had shorter duration of symptoms compared to those who were antibody negative (0.4 +/- 0.3 vs 4 +/- 1 months, p = 0.004). In dilated cardiomyopathy, antibody status was not associated with any clinical or diagnostic feature. CONCLUSIONS: Autoimmunity is involved in a subset of patients with myocarditis and with dilated cardiomyopathy, regardless of their geographical origin or immunogenetic background. The antibody frequency in our dilated cardiomyopathy series from Italy tended to be lower than in other countries. This may reflect reduced antibody levels with disease progression and/or the recognised feature that Mediterranean populations are often less susceptible to autoimmune disease.

[Lacking effect of timing of surgery in relation to the menstrual cycle on prognosis of breast cancer in premenopausal women]. / Mancato effetto della temporizzazione della chirurgia in relazione con il ciclo mestruale sulla prognosi del cancro della mammella nelle donne in premenopausa.

The influence of timing of surgery in relation to menstrual period on survival of breast cancer patients has been both advanced advocated and disputed. A meta-analysis on published series showed a statistically significant overall odds reduction when surgery is performed in the luteal phase. The records of 165 premenopausal M- breast cancer women, not on hormonal therapies, consecutively operated on from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus operative radiotherapy, Node-positive patients received standard adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pathological T and N. In each model, patients were divided into two groups according to the criteria proposed by Badwe, Hrushesky, and Senie. Multivariate analysis showed a significant association between pT and pN and survival, whereas no association with survival was observed for timing of surgery according to Badwe or Hrushesky or Senie criteria (RR = 1.26, RR = 0.91, and RR = 0.88 respectively). Up-to-date agreement on the menstrual phase and relative expected better prognosis is still lacking.