120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

[Indications for integrated surgical treatment of peritoneal carcinomatosis of colorectal origin: experience of the Italian Society of Locoregional Integrated Therapy in Oncology]. / Indicazioni al trattamento chirurgico integrato delle carcinosi peritoneali di origine colorettale: esperienza della società Italiana di terapie integrate locoregionali in oncologia.

A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was respectively 21.7% and 2.9%. Three years overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs CC 2 patients and PCI < or = 10 vs > 10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 overall survival rised up to 44.7% at 4 years. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-year showed a 50% disease-free survival at 5 years. In conclusion PCI < or = 10, complete or optimal cytoreduction feasibility and disease-free interval have to be considered for the patients selection to the integrate treatment.

Phase I-II study on isolation antiblastic fotemustine perfusion after dacarbazine chemosensitization for advanced melanoma of the extremities.

Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.

Sitilo experience on peritoneal carcinomatosis from colorectal cancer: clinical prognostic features.

UNLABELLED: A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was 21.7% and 2.9% respectively. Three-yrs overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs. CC 2 pts and PCI < or = 10 vs. >10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 4-yrs overall survival rised up to 44.7%. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-yrs showed a 5-yrs disease-free survival of 50%. CONCLUSIONS: PCI < or = 10, complete or optimal cytoreduction feasibility have to be considered for the patients selection to the integrate treatment. Disease-free interval seems to be a powerful prognostic indicator and deserve to be better outlined in further studies.

TNF-based limb perfusion for cutaneous melanoma in transit metastases: suggestions for modification of the perfusional schedule.

Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical difference for tumor response were seen for disease burden, ILP temperatures and duration. Our results showed that it is possible to modify the perfusion schedule, without compromising the response rate but with lower cost and toxicity.

A simplified procedure for continuous intraoperative external monitoring of systemic leakage during isolated limb perfusion.

AIMS: Isolated limb perfusion (ILP) with high doses of an alkylating agent alone or in combination with tumor necrosis factor (TNF) in hyperthermic conditions (HAP) has been proposed for the treatment of locoregional tumors. A critical step in ILP/HAP is accurate monitoring of systemic leakage to prevent the toxic effects of chemotherapy, and in particular of TNF. Ten percent systemic leakage from the perfusion circuit is considered the maximum acceptable leakage. In this study we report our experience of a new leakage monitoring system. MATERIALS AND METHODS: Ths new simplified procedure is based on the use of 99mTc-labeled soluble human serum albumin (HSA) and a hand-held gamma probe as detector. The procedure consists of the following steps: 1) A standardized 99mTc-HSA dose of 0.5 MBq/kg body weight is injected into the perfusion circuit before chemotherapy/TNF perfusion and a hand-held gamma probe (IGP) is placed over the precordial area in a zone that was marked on the skin during a simulation test; 2) 48-72 hours before ILP/HAP a complete simulation test is performed with a 99mTc-HSA dose corresponding to 10% of the total dose calculated for the patient's body weight; 3) during the simulation test the maximum count-rate zone on the precordial area is detected by IGP and marked on the patient's skin; 4) a 60-min curve of effective 99mTc-HSA radioactivity decay (physical and biological) is calculated and fitted; 5) to compare external counting with the effective circulating radioactivity, patient blood samples and circuit blood samples are taken every five minutes during ILP/HAP and measured by a laboratory gamma counter and very convenient thanks to the favorable characteristics of IGP. The placed in the operating room. RESULTS: External counting with a hand-held gamma probe was easy to perform time/activity curves obtained during simulation tests showed a regular and constant effective decay with a mean decay rate of 30% at 60 minutes compared to baseline values. The external measurements obtained by IGP proved to be well correlated with blood samples measured in vitro by a laboratory gamma counter. The results of this procedure, in particular the data of the simulation test for each patient, allowed us to correct the limit of 10% maximum leakage during ILP/HAP in accordance with the time/activity curve. CONCLUSIONS: Although 99mTc-HSA has some unfavorable characteristics, it offers many advantages over 131I-HSA. The procedure proposed by us, which was based on the use of an IGP and 99mTc-HAS at a standardized dose of 0.5 MBq/kg body weight and on an individual simulation test for each patient performed 48 hours before ILP/HAP, proved to be simple and accurate in monitoring systemic leakage during ILP/HAP anti-cancer therapy.

Isolated vascular perfusion of human colon with adenocarcinoma.

Based on the premise that optimal drug delivery might improve the efficacy of locoregional treatment for solid tumors, the authors set up an experimental model for isolation perfusion in surgical specimens from patients resected for carcinoma of the colon. Ten surgical specimens were cannulated, washed internally and externally with saline solution, promptly cooled to 4 degreesC, connected to a circuit, and perfused with Krebs-Henselait modified solution, concentrated red blood cells, albumin, desamethasone, glucose, and heparin for 60 minutes at a target temperature of 37 degreesC. Organ temperature, flow rate, perfusion pressure, and metabolic and functional parameters were checked at 5, 20, and 60 minutes of perfusion. A paraphysiologic perfusion procedure was achieved. Mean values (and ranges) were as follows: temperature 37 degreesC (35. 1-39.6 degreesC); flow rate 10.2 (5.6-17.9) ml/min/100 g; arterial pressure 96 (42-154) mmHg; arterial pH 7.3 (7.1-7.5); arterial PO2 183 (78-304) mmHg; arterial PCO2 36 (31-46) mmHg. No important signs of tissue damage were found at histology. Autonomous or stimulated peristalsis (or both) was present throughout the experiment. Mean O2 extraction was 7.9 ml/min/100 g (range 3.1-11.0). Mean glucose consumption was 229 mg/100 g (range 174-252). The model worked well and appears promising, particularly for future use in various pharmacokinetic and pharmacodynamic studies of antiblastic agents.

Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients.

BACKGROUND: Long term results after liver resection for hepatocellular carcinoma (HCC) are disappointing because the disease tends to recur. In this study, the authors assessed prognostic factors affecting long term outcome, in the hope that these factors might be used in selecting HCC patients for surgery. METHODS: During the period 1977-1995, 100 consecutive patients underwent curative liver resection; 78 of 100 had HCC arising on preexisting cirrhosis (53 Child's Class A and 25 Child's Class B). Thirty-five prognostic factors were evaluated for their association with overall survival (OS) and disease free survival (DFS) in univariate and multivariate analysis (Cox proportional hazards model). RESULTS: There were four postoperative deaths. Seven patients died in hospital of hepatorenal failure: six had Child's Class B cirrhosis and had undergone preoperative chemoembolization. Of the remaining 89 patients, 50 developed recurrence. All surviving Child's Class B patients had recurrence. Five-year OS, postoperative deaths included, was 38% (median, 36 months). Five-year DFS, postoperative deaths excluded, was 26% (median, 21 months). Independent prognostic factors for DFS were Child's class, glutamic-oxaloacetic transaminase, gamma-glutamyltransferase, alpha-fetoprotein, number of tumor nodules, width of resection margins, preoperative chemoembolization, and experience of the team that performed the surgery. Factors with an independent effect on OS were Child's class and width of resection margins. CONCLUSIONS: Liver resection can provide long term DFS in HCC patients with normal liver function. In patients with liver function impairment or an inadequate resection margin, recurrences are almost certain to occur. Preoperative chemoembolization significantly prolongs DFS but may increase the risk of postoperative liver failure in patients with liver function impairment.

Percutaneous endoscopic gastrostomy for feeding. A comparison between neurologic and neoplastic indications.

The most common indications for percutaneous endoscopic gastrostomy (PEG) are neurologic deficits precluding adequate oral nutrition. The aim of this study was to ascertain whether PEG is as feasible, safe and effective in patients with advanced oropharyngeal, oesophageal and pulmonary carcinoma as it is in patients with neurologic deficit. PEG, attempted in 108 consecutive patients, was successful in 100 (overall success rate of 92%). On the basis of primary disease, the patients were subdivided into two groups: patients with neurologic diseases (group A, n = 50) and patients with oropharyngeal, oesophageal and lung carcinoma precluding adequate oral nutrition (group B, n = 50). No statistically significant difference was found between the PEG placement success rates of the two groups. Of the patients PEG placement 1 died and 2 had major complications. 15 out of 50 patients in group A and 11 out of 50 in group B had minor complications. No statistically significant differences were found between the mortality and morbidity rates of the two groups. Duration of nutrition was similar in both groups. In particular, 46% group A patients and 46% group B patients were PEG-fed for more than 3 months. A wider use of PEG is suggested in patients with advanced oropharyngeal, oesophageal and pulmonary carcinoma precluding adequate oral nutrition.

Efficacy of dilatations for anastomotic colorectal stenoses: prognostic factors.

The authors report their experience of 30 patients with colorectal anastomotic stenosis treated by 62 dilatation sessions in order to evaluate which anastomotic characteristics could influence the success of dilatation therapy. Patients were subdivided into group A (dilatation successful) and group B (dilatation unsuccessful). Overall, dilatation was successful in 73.3% of cases, with only one important complication. The prognostic factors considered were anastomotic dehiscence, adjuvant radiotherapy, presence of colostomy at dilatation, site, morphology and length of the stenosis, presence of neoplastic recurrence, type of anastomosis and type of dilatation. Radiotherapy, local neoplastic recurrence and large anastomotic dehiscence were the more important independent prognostic factors. If present together, they were associated with an almost 100% probability of failure and, vice versa, if they were absent this probability was 5%.

Giant cavernous hemangiomas: diagnosis and surgical strategies.

From January, 1972 to June, 1989, 51 patients with liver hemangiomas (32 females and 19 males, mean age 35 years) were evaluated for surgical treatment. Diameters of the masses were 5 cm to 20 cm (median 8.5 cm). Nine of the patients had already been treated for cancer. Twenty-two (43.1%) of the 51 patients were symptomatic and 29 (56.9%) patients were asymptomatic. In 34 patients (66.7%) a definite diagnosis of hemangioma was made by scintiscan and/or ultrasound and/or computed tomography and/or angiography while in the remaining 17 (33.3%) patients the diagnosis was uncertain. The most common indications for resection were the presence of a symptomatic angioma, a symptomatic mass with an uncertain diagnosis, and/or lack of a definite pre-operative diagnosis. Surgery was performed on 25 patients. Ten anatomic and 15 atypical resections or enucleations were performed. There were no postoperative deaths. Two further patients, operated for probable hemangioma, were found to have primary hepatic malignancies. In the 26 unresected patients, no complications were observed during follow-up. In 3 patients, hemangioma enlargement was detected by ultrasound, but there were no symptoms. As cavernous liver hemangiomas are now more reliably diagnosed and their natural history is usually uneventful, surgery can be avoided in most cases. However, when a non-resection policy is adopted, an exact diagnosis is essential in order to rule out primary or metastatic cancer. Surgical exploration and treatment should be limited to symptomatic or complicated cases as well as to patients with an uncertain diagnosis.

Colorectal metastases to the liver: present results and future strategies.

In recent years, wide agreement has been expressed on the value of surgical resection for liver metastases from colorectal cancer, while for unresectable patients different types of locoregional treatment have been attempted. One hundred seventy-one patients with hepatic metastases from colorectal cancer were treated by us over a period of 15 years. Sixty-four underwent hepatic resection, and 107 underwent various forms of locoregional treatment. Our experience confirms the opinion that hepatic resection can be performed with a "curative" aim in patients with colorectal liver metastases: a 5-year survival rate can be achieved in about 30% of resectable cases. Adjuvant chemotherapy after hepatic resection should be tested in prospective randomized trials. Patients with diffuse liver metastases can benefit from locoregional infusion chemotherapy. Symptoms improve in most patients and objective responses are higher than those reported for systemic chemotherapy. Survival benefit with respect to untreated patients, has not yet been demonstrated by prospective randomized studies. Future improvements may be achieved by using new treatment modalities, such as new drug combinations, repeat arterial ischemia, and local tumor destruction. As these types of treatment are still experimental they should be employed only in prospective clinical trials.

Colorectal metastases to the liver: present status of management.

The management of patients with hepatic metastases from colorectal carcinoma is controversial. While a "no treatment" attitude still persists, other patients undergo systemic chemotherapy with very limited results. Other possible options are hepatic resection and locoregional treatments. One hundred twenty-three patients with hepatic metastases from colorectal cancer were treated at the authors' institution over a period of 15 years. Thirty-nine patients underwent hepatic resection while 84 underwent various forms of locoregional treatment. Several patients in the latter group were registered in one national (RNSI) Phase 2 study and one international (EORTC) Phase 3 trial. The authors' experience confirms the opinion that hepatic resection can be performed with the aim of curing in patients with isolated metastases. A five-year survival rate can be achieved in 25 to 30 percent of the resectable patients. Patients with unresectable extrahepatic disease or multiple bilateral metastases are usually excluded from resection. In other cases, hepatic resection should be carried out when technically possible. The value of adjuvant chemotherapy to the remaining liver has to be tested in prospective randomized trials. Patients with diffuse metastases can benefit from locoregional infusion of chemotherapeutic agents. Symptoms improve in most patients; objective responses vary from 53 to 83 percent of the cases, which is a higher rate than that reported for systemic chemotherapy. Survival may be prolonged in respect to untreated patients but this has not been demonstrated yet by prospective randomized studies. Current trends are continuous infusion of chemotherapeutic agents and experimentation of new drugs or drug combinations. Future improvements may be achieved by adding hepatic arterial ischemia, hyperthermia, or radiation therapy. As these kinds of treatments are still experimental, they should be applied to the patients only in the context of prospective clinical trials.

[Hemobilia caused by an intrahepatic aneurysm]. / Emobilia da aneurisma intraepatico.

The authors describe one case of hemobilia for intrahepatic aneurysm treated successfully with the placement of Gianturco's stainless steel coil during hepatic arteriography.