Retroperitoneal or mesenteric primary liposarcoma: clinical and prognostic evaluations on five cases.

BACKGROUND: Retroperitoneal or mesenteric primary liposarcoma is a malignant neoplasia whose prognosis depends on the biological variants, the radical resection surgery and the histological subtypes, as well as on local and remote recurrences. Liposarcoma is the most common variant of this tumour among tumours of soft retroperitoneal tissue. The purpose of this study is to evaluate whether the treatment of this disease, carried out at the Ivrea Hospital for urgent reasons, may be considered in line with the experience of high-volume Centres. PATIENTS AND METHODS: Between 1982 and 2016 five patients were hospitalized with a diagnosis of acute abdomen due to retroperitoneal or mesenteric primary liposarcoma: one myxoid of the mesentery, one well-differentiated of lesser epiploon, one well-differentiated of mesentery, and two dedifferentiates of the retroperitoneum. RESULTS: The five patients, all males, had a average age of 59 years (range 48-86) and were all subjected to general anaesthesia and open technique for total tumour removal. Only the patient with the myxoid liposarcoma had two recurrences. All are alive and healthy after a follow-up of 177 months (range 9-420). CONCLUSION: These tumours should be removed radically, if necessary in conjunction with contiguous organs. Rarity and therapeutic complexity require a treatment, sometimes even multimodal, in highvolume centres. Patients admitted in General Surgery Unit for unpostponable urgency should be operated by surgeons experienced in the treatment of abdominal disease to achieve survival results in line to those achievable in Hub Centres.

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Efficacy of fleece-bound sealing system (TachoSil®) in delayed anterior tracheal lacerations secondary to ischemic tracheal necrosis after total thyroidectomy.

Thyroidectomy is one of the commonest surgical operations performed in endocrine surgery; results are generally excellent and morbidity and mortality usually are negligible. Total thyroidectomy's complication rates are low, with an overall incidence of 4.3% among experienced surgeons: the most frequent complications are vocal cord paresis or paralysis, hypoparathyroidism, hypocalcemia, haematoma and wound infection. Tracheal injury following thyroidectomy is even more rare. As reported from some authors, inadvertent tracheal injury has an incidence of 0-0.6% during thyroidectomy. Tracheal laceration (generally located in the posterolateral surface) is often recognized and repaired immediately, during the same intervention. Rarely, following a total thyroidectomy, a delayed tracheal rupture may occur secondary to an ischemic damage of the trachea. This has been described in few cases reported in literature. In this paper we report of a case in which delayed tracheal lacerations appeared 10 days after the patient underwent total thyroidectomy: a prompt surgical operation was efficient using both direct sutures of tracheal breaches and a patch of fibrinogen-thrombin coated collagen fleece covering the entire surface.

Interposition of the gallbladder in the common hepatic duct: a rare dangerous anomaly. Case report.

INTRODUCTION: Anomalies of the gallbladder position in the biliary tract are rare, but they could be very dangerous during cholecystectomy. CASE REPORT: A 48-year-old man presented with a 2-week history of intermittent epigastric pain, scleral jaundice and elevation of liver function tests. After a magnetic resonance cholangiogram and an endoscopic retrograde cholangiogram with sphincterotomy, he was submitted to laparoscopic cholecystectomy, the conversion to laparotomy was decided for the suspect of gallbladder interposition. The anatomical anomaly was confirmed and a Roux-en-Y hepaticojejunostomy was executed, with end-to-side anastomosis between the confluence of the hepatic ducts and the fourth loop of jejunum, on a biliary stent. This catheter was removed in the tenth postoperative day; after cholangiography and CT abdominal scan the patient was discharged, without complications. CONCLUSION: The gallbladder interposition is a rare malformation which seems to arise from an embryonic anomaly occurring between the 4th and the 5th week and whose potential causes have not been detected. A similar outcome could be also determined by a Mirizzi syndrome, but in our case it is excluded because intra-operatively there was no inflammatory reaction that could justify the presence of a fistula between the gallbladder and the common hepatic duct. Once the gallbladder interposition is found, the surgical treatment consists in removing the gallbladder itself and the corresponding part of the common hepatic duct. The reconstruction is carried out by a Roux-en-Y hepaticojejunostomy with anastomosis at the hepatic hilum, positioning a biliary stent.

Unilateral phrenic nerve paralysis: a rare complication after total thyroidectomy for a large cervico-mediastinal goitre.

Unilateral phrenic nerve paralysis is a rare complication of cervico-mediastinal goitre. It occurs when adhesions grow between the intrathoracic part of the thyroid and the nerve, specially where the goitre enters the mediastinum behind the first rib. The damage may be caused by strain of the nerve due to the descent of the goitre into the chest or may be caused by the surgical manoeuvres during thyroidectomy performed by cervical approach. Two patients operated on for large cervico-mediastinal goitre are reported: a 70-year-old male with a large intrathoracic growth of the left thyroid lobe and a 54-year-old male with a large intrathoracic growth to the right lobe. A few days after total thyroidectomy they showed signs of exertional dyspnoea. The exams performed showed hemi-diaphragm relaxatio due to phrenic nerve paralysis, with resulting reduction of respiratory space. Phrenic nerve paralysis may follow total thyroidectomy for large cervico-mediastinal goitres; is not due to the operative technique, but rather to the particular anatomic conditions which may be found.

[Intra-abdominal desmoid tumors: rare but important disease]. / I tumori desmoidi intra-addominali: una patologia rara, mai importante.

Desmoid tumors are rare benign neoplasms with high tendency to local recurrence, and they can be divided into extra- and intra-abdominal types (mesenteric fibromatosis). Eight cases have been treated in our Department from 1997 to 2006. Six patients (3 men and 3 women) affected by extra-abdominal desmoid tumors have been treated with radical excision. In two patients desmoid was intra-abdominal: 1) a 55 years old man admitted for acute abdomen and submitted, in emergency, to a laparotomy with excision of a mesenteric abscess including a jejunal loop at about one meter from Treitz; 2) 52 years old man, submitted to an elective excision of a capsulated neoplasm of the little omentum, which had caused an oppressive abdominal pain. In both cases the hystological diagnosis has been desmoid tumor. Surgical treatment of desmoid tumors must aim at radical excision to avoid frequent recurrences (25-65%); these have stimulated the research of other kinds of treatments, since a new surgical operation itself can lead to a further recurrence. Radiotherapy has been investigated with results in 79-96% of cases, antiestrogenic therapy has been used with success in 51% of patients, and high dose tamoxifen seemed to obtain a stable disease in non operable cases. Non steroidal anti-inflammatory drugs have been experimented in association with tamoxifen and chemotherapy. Conclusive results on the efficacy of these treatments have not been obtained yet, because of the rarity of the desmoid tumors even in greater Centres.

[Stapled versus hand sewn anastomosis in elective and emergency colorectal surgery]. / Anastomosi meccanica versus manuale in chirurgia colorettale elettiva d'urgenza.

We studied the incidence of anastomotic leakage in colorectal surgery with the alternative use of stapled anastomosis, hand sewn anastomosis and stapled/hand sewn anastomosis. 477 consecutive patients admitted for elective or emergency colon surgery were divided in: Group I? 337 elective patients submitted to mechanical bowel preparation; Group II - 140 emergency patients operated without mechanical bowel preparation. We analyzed surgical complications in the two group considering the different anastomosis made (stapled, hand sewn and stapled/hand sewn). Anastomotic leakages were 11 (3.3%) in Group I: 7 in stapled (3,4%), 2 in hand sewn (2,1%) and 2 in stapled/hand sewn anastomosis (5,3%); 10 patients (91%) with peritonitis or intra-abdominal abscess required re-intervention and there was a correlated death. In Group II there were 6 anastomotic leakages (4,2%): 1 in stapled (1,4%), 3 in hand sewn (8,3%) and 2 in stapled/hand sewn anastomosis (5,7%); four patients required re-intervention and there were no correlated deaths. Mean postoperative stays were similar among the different techniques of suture in the two groups. No statistically significant differences in surgical complications were noted among stapled, hand sewn and stapled/hand sewn anastomosis. The choice should be based on personal preference and surgeon experience, considering costs, using hand sewn suture whenever is possible.

[Incidence of complications of thyroid surgery]. / Incidenza delle complicanze nella chirurgia della tiroide.

BACKGROUND: Thyroid surgery presents a low incidence of complications. Death is certainly a rare, or even exceptional event. Hypoparathyroidism, above all if definitive, is the main complication of total thyroidectomy with percentages that very between 0 and 10% in the literature (average 2%). METHODS: The incidence of recurrent lesions varies between an improbable 0% to 8%, whereas lesions to the superior laryngeal nerve are relatively frequent, but often undervalued. Dysphagia, although always transient, presents a high risk of pneumonia ab ingestis and severe dehydration. Hemorrhage has an incidence of 0.1-3.8% and infection is reported in approximately 1% of cases. The permanent and recurrence nature of thyroid pathology in literature is between 5 and 11%, resulting from inadequate or sometimes useless surgery. Hypothyroidism is the logical consequence of total thyroidectomy. In the light of these data we have re-examined 300 operations involving thyroid pathology performed by the same team using the same method over the past 4 years (82% females, 18% males). 33% of the cases presented benign euthyroid nodular pathology, 27% hyperfunctioning benign nodular pathology, 2.6% Flajani-Basedow-Graves disease, 9% were adenomas, 7% were differentiated carcinomas, 2% anaplastic carcinomas and 0.7% medullary carcinomas. 99 extracapsular total loboisthmectomies, 135 total extracapsular thyroidectomies and 66 subtotal thyroidectomies were performed. RESULTS: The following complications were observed: 31/300 symptomatic hypocalcemias of which 25 were transient and 6 (2%) were definitive but easily controlled with treatment; 9 recurrent monoplegias out of 501 isolated recurrent forms of which 4 (0.8%) was permanent; 5/300 (1.7%) postoperative dysphagias associated with recurrent monoplegia in 4 cases. Damage to the external branch of the superior laryngeal nerve was suspected in 11/300 cases (3.7%). Postoperative hemorrhage occurred with an incidence of 1.3%, whereas the incidence of wound infection and serous collection was 1.7%. Moreover, persistent hyperthyroidism after subtotal bilateral thyroidectomy was observed secondary to toxic plurinodular struma. A case of paralysis of the right ulnar nerve, when the arm was adducted, was observed on the operating table, but regressed after about 4 months. Mortality was zero. CONCLUSIONS: Thyroid surgery is still hampered by a relatively low percentage of complications, which are probably still the result of various technical limitations, and it appears difficult to reduce these, let alone eliminate them completely.

[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.

[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.

[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.

Timing of surgery related to menstrual cycle and prognosis of premenopausal women with breast cancer.

The influence of the timing of surgery in relation to the menstrual cycle on the survival of breast cancer patients has been both advocated and disputed. The records of 165 premenopausal M- breast cancer women consecutively operated from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus postoperative radiotherapy. Node-positive patients received adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pT and pN. 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 the timing of surgery according to either Badwe or Hrushesky or Senie (RR = 1.26, RR = 0.91 and RR = 0.88 respectively). Consensus on the menstrual phase related to the expected best prognosis is still required.

Conventional isolated hyperthermic antiblastic perfusion in the treatment of recurrent limb melanoma.

Hyperthermic Antiblastic Perfusion (HAP) is a widely used method for the treatment of recurrent limb melanoma. In terms of tumor response, locoregional control and survival HAP has led to better results than those achieved with any other treatment. The aim of this report is to analyze our own experience with HAP in locally advanced limb melanoma. Thirty-two patients were submitted to HAP. HAP lasted 60 minutes, with maximal local temperature of 40.5-42 degrees C using melphalan 10 mg/L limb volume as antiblastic agent. Twenty patients had in-transit metastases and 12 local recurrence. Regional nodes were involved in 12 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5-30% (mean 14%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 8 patients, grade II in 17, grade III in 6 and grade IV in 1 case. Response rate (UICC) in the 16 patients treated with unexcised lesions was 94% (56% complete responses). With a median follow-up of 29 months (2-126) 14 patients relapsed after a median time of 10 months, and 17 patients are currently disease free, 3 of these are being reexcised and 3 re-perfused. Actuarial 5 years survival was 64%, with 39% disease free to the first relapse. Our results are consistent with the literature indicating HAP as a safe procedure with a high evidence of clinical responses.

[Function and complications of diverse totally implantable systems for continuous intra-arterial infusion of FUdR in colorectal hepatic metastases]. / Funzionalità e complicanze di diversi sistemi totalmente impiantabili per l'infusione intraarteriosa continua di FUdR nelle metastasi epatiche colo-rettali.

Different totally implantable arterial infusion systems were compared in patients with liver metastases from colorectal cancer undergoing continuous intra-arterial infusion. Seventy-eight patients received continuous FUdR infusion using either totally implantable pumps (group a = 44 pts.) or ports fed by external portable pumps (group b = 34 pts.), and 57 patients received bolus infusion of Cisplatin (group c). Devices were cared for patency even after interruption of treatment, commonly caused by disease progression. Pocket problems most frequently occurred in group a (30%) compared to groups b (9%) and c (7%), whereas a higher incidence of catheter and infusion related problems was observed in group b (109%). System failure was recorded as a cause of interruption of treatment in two, 9, and 6 cases in groups a to c, respectively. The 12-months patency rate was 92% in group a, 24% in group b (median 9 months), and 65% in group c (median 17 months). Though implantable ports allow adequate infusion periods in most cases they seem more adequate for bolus infusions.

[Surgical treatment of inguinal hernia using a "tension-free" technique and local anesthesia. Initial experience]. / Trattamento chirurgico dell'ernia inguinale con tecnica "tension-free" in anestesia locale. Eperienza iniziale.

Between January, 1991 and December, 1993, 208 subjects with monolateral and 19 with bilateral inguinal hernia were submitted to herniorrhaphy. Thirty-four were recurrent hernias. All but one bilateral hernias were treated at the same time. Eight cases were operated in emergency condition for acute strangulated hernia. Two-hundred and ten operations were performed under local, 17 under general and 1 under spinal anesthesia. Herniorrhaphy was performed in 14 cases with the Bassini and in 38 with the Shouldice technique. In 191 instances the "tension-free" and in 3 the "plug" techniques were adopted utilizing a polypropylene mesh. Following local anesthesia 13 episodes of bradycardia with hypotension were recorded during the operation and 4 in the early postop period. There were no general complications. Two elderly patients developed urinary retention following general anesthesia. Local complications included 6 (2.4%) cases of infection and 4 (1.6%) cases of hematoma of the wound, and 5 (2.0%) cases of edema with infiltration of the cord. Percentage of follow-up at 1, 2 and 3 years was 96, 95, and 93 percent respectively. Five recurrences were recorded: in 1 case following Bassini repair (7.6%), in 2 following Shouldice (5.6%), and in 2 following tension-free (1.5%). Local anesthesia has been confirmed to be well accepted by the patients, effective an safe, especially in the elderly patients with high operative risk. Similarly, the tension-free hernioplasty has been confirmed as a simple, easily reproducible technique, followed by less pain and disability as compared with other types of herniorrhaphies, and more effective mainly in the treatment of recurrent hernia.

Palliative chemoembolization of hepatocellular carcinoma with mitoxantrone, Lipiodol, and Gelfoam. A phase II study.

Transcatheter chemoembolization, in conjunction with various drugs, has been widely used for palliative treatment of hepatocellular carcinoma. A phase II study was carried out on mitoxantrone chemoembolization. High risk cirrhotic patients were excluded from this study. Fourteen mg/m2 mitoxantrone and up to 20 ml Lipiodol were injected, followed by Gelfoam embolization as indicated. Thirty-seven patients (33 with cirrhosis) were treated. Sixty-nine cycles were delivered, 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 received Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. No treatment-related deaths occurred. Complications were mild and transient, including nausea/vomiting in most cases, fever over 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 responses) 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 appears to be a promising method for the palliation of advanced hepatocellular carcinoma, and deserves to be evaluated in well controlled randomized studies.

Effect of hyaluronidase on the pharmacokinetics of free and total platinum species after intra-arterial Cisplatin in refractory patients with colorectal liver metastases.

A pharmacokinetic study was carried out in patients with unresectable colorectal liver metastases who had primarily been included in a phase II trial of intra-arterial cisplatin (DDP) plus intravenous fluorouracil. Ten patients of those accrued for the clinical study underwent the pharmacokinetic investigation upon liver progression of the disease. Four patients were treated with DDP (24 mg/m(2)) through short intra-arterial infusion (baseline study) and 4 patients received intra-arterial hyaluronidase (HY, 100 000IU) 2 minutes before DDP infusion. Two additional patients were treated with both DDP alone and DDP + HY. Plasma concentrations of total and free platinum (Pt) were consistently lower than baseline in the presence of HY. HY administration resulted in a longer terminal half-life (2.1 ± 0.7 vs 1.0 ± 0.2 days, p < 0.05), a reduced area under the plasma concentration-time curve from 0 to 2 hours (AUC0-2h) [0.08 ± 0.009 vs 0.12 ± 0.017 g/L•min, p < 0.01], and an increased volume of distribution, both initially (11.7 ± 3.4 vs 6.6 ± 2.1L, p < 0.05) and at steady-state (43.0 ± 10.8 vs 22.1 ± 8.8L, p < 0.05), for total Pt. However, significant HY-related effects on the overall plasma exposure (AUC0-∞) to total Pt or on the total body clearance were not observed. HY treatment was also associated with a lower plasma concentration at time zero (C0) [p < 0.01 ] and AUC0-2h (p < 0.02), and a higher plasma clearance (p < 0.02) and apparent volume of distribution (p < 0.05), for free Pt. Renal clearance (CLR) and cumulative urinary excretion of Pt were significantly increased (p < 0.01) by HY, while fluid output was not significantly affected. The increase in both CLR and the extent of Pt distribution was not due to a protein binding drug interaction nor to a reaction between DDP and HY in the plasma. Combined treatment with HY yielded a clinically acceptable toxicity.