Hepatic intra-arterial injection of 1,25-dihydroxyvitamin D3 in lipiodol: Pilot study in patients with hepatocellular carcinoma.

1,25-dihydroxycholecalciferol [1,25-(OH)2 D3] has been shown to have antiproliferative effects in a wide variety of cancer cell lines. In vivo studies, although often limited by the development of hypercalcemia, have also shown the potential usefulness of 1,25-(OH)2 D3 in inhibiting tumor growth. The potential usefulness of the drug has been hampered by the development of hypercalcemia. This pilot clinical study was designed to evaluate the preclinical results that have shown, locoregional administration of 1,25-(OH)2 D3 in lipiodol can prevent the development of hypercalcemia. Eight patients with refractory HCC were given a single intrahepatic arterial dose (50, 75 or 100 microg) of 1,25-(OH)2 D3 dissolved in 5 ml of lipiodol. Following this, for 4 weeks serum calcium, 1,25-(OH)2 D3, alpha-fetoprotein and a range of biochemical indices were monitored. While, in 3 patients the calcium levels exceeded the normal range, even at these extremely high doses, non of the patients developed grade 3 hypercalcemia. 1,25-(OH)2 D3 administration also led to transient stabilization of serum alpha-fetoprotein in these patients. The data obtained support the hypothesis that, in patients with HCC, locoregional delivery of 1,25-(OH)2 D3 in lipiodol can allow administration of supra-pharmacological doses of the drug without the development of hypercalcemia.

The sentinel lymph node biopsy in breast cancer.

OBJECTIVE: To evaluate the possibility and accuracy of this new diagnostic approach to the breast cancer disease in our centre. MATERIAL AND METHODS: Since March 1999, every patient presenting with a cT1-T2 N0 breast carcinoma was scheduled for a sentinel lymph node search. An injection of Tc-99 labelled nanocolloïd with a dose of 1 mCu was injected either intramammary or intradermally. The patients have been divided into two groups: in group I, they received their injection intramammarily the day before the operation; because of several failures in identifying the sentinel lymph node (SLN), the protocol was modified, the patients receiving their injection the day of operation, intradermally (group II). Once a lymphoscintigraphy done, the SLN was identified at operation using a detection probe, after the primary tumour had been removed. A routine axillary dissection was then performed to remove the rest of the lymph nodes. All the nodes were then checked routinely for metastatic cells. The SLN was also screened by semi-serial slides and by immuno-assay. RESULTS: From March 1999 till March 2001, sixty patients presented consecutively with a T1 or T2 biopsy proven breast carcinoma with no clinical lymph nodes. They were all scheduled for a sentinel lymph node search according to the protocol. Mean tumour size was 9.9 mm (ranging from 4 to 23 mm). Fourteen patients (group I) received their injection intramammarily but we failed to identify the sentinel node in five patients (35%). The remaining forty-two patients (group II) received their injection intradermally. Sentinel nodes were then identified in forty-three patients (93%). Positive SLN were discovered in eleven cases by routine examination (13 positive nodes among 104 harvested sentinel nodes, i.e. 13%). Micro metastases were discovered in three other SLN by immunohistology. In total, 605 lymph nodes were evaluated through the axillary dissection, representing a mean number of 10.08 lymph nodes per patient. For four patients, positive lymph node were discovered in the axillary dissection while SLN were negative (6.6% of false negative). CONCLUSIONS: During this learning curve period, it appears that the method for screening the SLN is reliable, since the figures encountered are similar to those of the literature. By adding a perioperative blue dye injection, it might be possible to reduce the percentage of false negative results. It is difficult to assess, at present, the impact SLN could have on survival.

Reduction in recurrence risk for involved or inadequate margins with edge cryotherapy after liver resection for colorectal metastases.

HYPOTHESIS: The usefulness of additional edge cryotherapy after liver resection for liver metastases from colorectal cancer to improve involved or inadequate (less than 1 cm) margins is uncertain. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of surgery at a university hospital. PATIENTS: Eighty-six consecutive patients with hepatic metastases from colorectal cancer in whom we applied additional edge cryotherapy to involved or inadequate margins. This group was compared with 134 patients who underwent resection without edge cryotherapy (control group) during the same period. INTERVENTION: Potentially curative treatment was achieved by adding edge cryotherapy to insufficient resection sites in patients not eligible for further resection. MAIN OUTCOME MEASURES: Edge recurrence rate in the study group; validation of an additional treatment to improve curative resectability; and comparison of morbidity and local recurrence rates with the control group. RESULTS: At a median follow-up of 39 months, 47 patients were alive and 39 had died. Local recurrence at the resection site was diagnosed in 9 patients (10%), of which 7 occurred in patients with involved margins and 2 in patients with resection margin less than 1 cm. Thirty-six patients (42%) experienced recurrence in the remnant liver. Extrahepatic recurrence occurred in 38 patients (44%), the lungs being the most common site (22 patients [26%]). CONCLUSIONS: Edge cryotherapy is a potent additional surgical treatment option in patients with liver metastases from colorectal cancer. The percentage of patients who can be treated for cure can be increased, especially if complex liver surgery is demanded.

Pilot study of albendazole in patients with advanced malignancy. Effect on serum tumor markers/high incidence of neutropenia.

Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or alpha-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5-10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.

Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment.

HYPOTHESIS: Intraoperative echogenic appearance of liver metastases from colorectal cancer is a prognostic factor of outcome after curative treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of Surgery at a university hospital. PATIENTS: One hundred forty-three consecutive patients with hepatic metastases from colorectal cancer who underwent liver resection with curative intent between 1992 and 1998. INTERVENTION: Curative treatment was achieved by liver resection alone, liver resection plus edge cryotherapy, or liver resection plus cryotherapy to lesions not amenable to further resection. In patients with more than 2 lesions, a hepatic artery catheter was placed for regional chemotherapy. MAIN OUTCOME MEASURES: The echogenic appearance of the liver metastases was assessed by intraoperative ultrasound by a single person throughout the study using a 5-MHz ultrasound probe. The findings were prospectively entered into the database. RESULTS: Fifty-four percent of patients had hyperechoic metastases. This group had significantly longer overall (log rank, P<.001) and recurrence-free survival (log rank, P =.004) compared with patients who had hypoechoic metastases (36%). A significantly higher percentage of mucin-secreting tumors were found in the hypoechoic patient group (chi(2), P =.001). Dukes stage of the primary tumor (P =.02), echogenicity of the liver secondaries (P =.04), and diameter of the largest resected metastasis (P =.01) were independent prognostic factors for recurrence-free survival in the Cox regression model. CONCLUSION: These results support the hypothesis that echogenicity of liver metastases from colorectal cancer is an independent prognostic factor of outcome after curative resection.

Hepatic intra-arterial injection of lipiodol-1,25-dihydroxyvitamin D3 for hepatocellular carcinoma in rats.

BACKGROUND: 1,25-(OH)2 D3 has an in vitro growth regulator effect on different cancers. Unfortunately, dose-limiting toxicity (hypercalcemia) limits its use in anticancer therapy. For primary liver tumors, loco-regional delivery of 1,25-(OH)2 D3 in lipiodol might avoid high systemic concentrations and development of hypercalcemia. MATERIALS AND METHODS: 1,25-(OH)2 D3 alone or mixed in lipiodol, was delivered at different concentrations into the hepatic artery of rats bearing a primary liver tumor. Calcium levels, tumor volume and proliferation index were assessed after treatment. RESULTS: Serum calcium values were significantly lower when the drug was mixed into lipiodol. Treatment with 10 micrograms of 1,25-(OH)2 D3 in ethanol resulted in a decrease in proliferation index within the tumor. CONCLUSIONS: The delivery of 1,25-(OH)2 D3 mixed in lipiodol reduces the subsequent elevation of serum calcium. Locoregional treatment with 1,25-(OH)2 D3 was shown for the first time to be effective on primary liver tumor growth in vivo.

Treatment of failed native arteriovenous fistulae for hemodialysis by interventional radiology.

BACKGROUND: We studied the feasibility, technical problems, safety, and effectiveness of percutaneous declotting of thrombosed native arteriovenous fistulae for hemodialysis. METHODS: Between 1992 and 1998, 93 declotting procedures were performed in 73 consecutive upper limb native fistulae (forearm 56 and upper arm 17), and 162 procedures were performed in 78 prosthetic grafts using manual catheter-directed thrombo-aspiration, with or without previous urokinase infusion. Detection of restenosis by clinical surveillance led to redilation or stent placement. Rethrombosis in four forearm and six upper arm fistulae were treated by 20 further declottings by aspiration. RESULTS: The initial success was 93% in the forearm and 76% in the upper arm (99% in grafts). The complications included one pulmonary embolism, one acute pseudoaneurysm, and one blood depletion requiring transfusion. Primary patency rates at one year were 49% in the forearm and 9% in the upper arm (14% in grafts). Secondary patency rates were 81 and 50% at one year, respectively (83% in grafts). Reinterventions were necessary every 19.6 months in the forearm and every 5.7 months in the upper arm (every 6.4 months in grafts, P < 0.05). Stents were placed in 11% of forearm fistulae and in 41% of upper arm fistulae (45% of grafts) for treatment of acute rupture (5 out of 19), stenosis recoil (6 out of 19), and early (< 6 months) recurring stenosis (8 out of 19). CONCLUSIONS: The percutaneous declotting of forearm fistulae by manual catheter-directed thrombo-aspiration was effective in more than 90% of cases and yielded 50% primary and 80% secondary patency rates at one year. The results were poorer in upper arm fistulae. The need for maintenance reinterventions was three times smaller in forearm fistulae than in upper arm fistulae and grafts.

Acalculous gallbladder pain: a largely unrecognised entity.

AIM: To study the presentation for and outcome of cholecystectomy in patients with acalculous gallbladder pain. METHODS: Sixty-six consecutive patients with prospective documentation underwent cholecystectomy for putative acalculous gallbladder pain between December 1988 to April 1995. The diagnosis was made on clinical grounds, but in the majority, a CCK oral cholecystogram was performed. Outcomes were assessed by postal questionnaire mailed in October 1995 or by the last recorded follow- up. RESULTS: Fifty-eight females and eight males, with a median age of 37.5 years had experienced abdominal pain, usually with associated nausea, for a median of three years. Preoperative investigations were non-contributory, with the exception of the CCK oral cholecystogram which was regarded as abnormal in all instances. At a median follow-up of 40 months, 48 patients (72.7%) described their symptoms as either totally relieved or much improved by cholecystectomy. CONCLUSION: Though the pathophysiology remains poorly understood, there is clearly a group of patients who suffer from gallbladder pain in the absence of gallstones and who benefit from cholecystectomy.

Hepatic resection for metastases in colorectal carcinoma.

AIMS: To outline the role of liver resection in the treatment of colorectal liver metastases, with particular reference to hospital morbidity, mortality and subsequent survival. METHODS: Seventy major liver resections were performed in Wellington by the senior author (RSS) between 1987 and 1997 for colorectal metastases. Fifty-three entailed resection alone with intent to cure, nine were associated with additional cryotherapy and in eight hepatic arterial chemotherapy was subsequently given. Resection was the initial form of liver treatment in all 70 patients. Patients were aged between 29 and 76 years with a median of 60.0 years. All patients were judged pre-operatively to have tumour confined to a resectable portion of the liver. Data were collected prospectively and held in a computerised database. Follow-up was available on all patients. RESULTS: Median operating theatre time was five hours and median blood loss was 1500 mL (60 mL-25 L). Eighty percent of resections entailed four or more liver segments. Postoperative morbidity occurred in 26 (37.1%) and 30-day mortality was 5.7%. Median hospital stay was 11 days (2-67). In the 53 patients who underwent resection alone, the three and five-year actuarial survival rates, including the 30-day mortality, were 62.0% and 27.2%, respectively. Dukes stage of the primary was the only significant prognostic factor found in this subgroup of patients (p<0.05). CONCLUSIONS: Resection of colorectal liver metastases can achieve extension of life and long-term survival in selected patients. However, it remains a major undertaking and is probably best performed in units with appropriate expertise and experience.

Gastric endoluminal treatment of Dieulafoy's ulcer.

Dieulafoy's ulcer, accounting for approximately 5% of upper GI bleeding, is best managed by therapeutic endoscopy. Some patients, however, require surgical treatment. Presented here is a case in which the lesion was treated by combined endoscopy and endogastric surgery. To the authors' best knowledge, this is the first published report of such management. This relatively new technique may be offered in suitable cases but should be attempted only by well-trained laparoscopic surgeons.

Percutaneous biopsy of operable liver lesions: is it necessary or advisable?

AIM: The necessity and desirability of performing percutaneous biopsy of potentially resectable liver tumours is called into question. METHODS: Two cases are reported in which percutaneous biopsy of resectable liver tumours was performed unnecessarily and resulted in needle track seeding. RESULTS: In both instances patients who underwent potentially curative liver resection were rendered incurable because of biopsy track recurrence. CONCLUSION: The common practice of performing percutaneous ultrasound or CT guided biopsy of potentially resectable lesions in the liver is generally neither necessary nor desirable.

[Possible release of aluminum from activated charcoal filters used in home hemodialysis]. / Libération possible d'aluminium à partir des filtres de charbon actif utilisés pour l'hémodialyse à domicile.

In 1984, 38 sera from home hemodialysis patients were found with a significant increase of aluminum (Al) from 67.8 +/- 44.3 to 102.0 +/- 45.9 micrograms/l (p less than 0.001) compared to 1983. The only change was an activated charcoal (AC) filter in the water treatment circuit, added downstream of the water softener. Five different home hemodialysis AC filters were tested: Microclean CA Dia Cuno, Traitement Standard des Eaux (TSE)R, Permo, C2R, Gambro. AC was shown to be the main source of Al, its content ranging from 1251 +/- 116 to 7569 +/- 969 mg/kg. Al released in 2000 l of liter rinsing water varied from 1.6 +/- 1.3 to 41.3 +/- 5.5 mg. (mean concentration: 0.8 to 20.6 micrograms/l): Gambro less than or equal to C2R less than TSE less than Permo less than Cuno (p less than 0.01). Al loading of charcoal could occur either before or during the activation process, by contaminated water, other added substances, or during packaging. In conclusion, our study suggests, first, to put AC filters upstream of Al captor to avoid Al intoxication, second, to systematically dose Al and may be other metallic substances in every manufactured AC sold for therapeutic purpose.

[Metabolic evaluation in urinary lithiasis. What is a reasonable level? 1: Theoretical approach]. / Bilan métabolique des lithiases urinaires. Jusqu'ou aller raisonnablement? 1re partie: l'approche théorique.

Whereas the etiology of urinary calculi and their metabolic exploration should be known, it appears unreasonable to conduct exhaustive metabolic explorations in all patients, therapy being usually symptomatic and based on advice on hygiene and diet. However, etiologic diagnosis is essential in a small number of cases: those which could benefit from effective preventive and curative measures and for which morbidity is elevated: cystinuria, hyperparathyroidism, uric acid calculi, patients at high developmental risks. It is possible, by simple, low cost means to select 95% of these patients. After a theoretical study of the distribution and lithiasic etiology, a practical conduct is proposed which takes into account the cost-effective ratio.

[Metabolic evaluation of urinary calculi. What is a reasonable limitation? 2: Practical approach]. / Bilan métabolique des lithiases urinaires. Jusqu'où aller raisonnablement? 2e partie: l'approche pratique.

There appears to be little justification for conducting major metabolic screening for all cases of urinary calculi, both because of the cost, and the weak therapeutic advantages faced with the increased urine output. It is more logical to use simple methods to distinguish two groups of patients: Those in whom the affection is easily curable: dietary excess, abuse of therapeutic means, hyperparathyroidism, uric acid stones. Those in whom the affection may become worse: cystinuria, urinary malformations, recurrent calculi. Simple investigations in all patients should be: Antecedents, regimens, drugs. Radiography, analysis of stones, allowing for errors. Cystinuria, urinary pH. Creatininemia, uricemia, calcemia. Examinations must be performed effectively, even in outpatients, and the results read (not always the case). For patients at risk, discovered initially or only after this first selection, excretion anomalies are investigated, only a few of them being submitted to a Pak's test.

[Vaccination against hepatitis B in a hemodialysis unit. A 4-year follow up (author's transl)]. / Vaccination contre l'hépatite B dans une unité d'hémodialyse. Etude sur une période de 4 ans.

From February 1976 to January 1980, 123 staff members and 84 hemodialysis patients were immunized against hepatitis B in an adult hemodialysis unit. The vaccine was prepared by purification of HBs Ag from human sera and was formalin inactivated. Vaccines were tested for seric markers of HB virus (HBs Ag, anti-HBs, anti-HBc) and serum transaminases (ALT, AST) before immunization and every month during the follow up. Tests for markers of auto-immunity were performed. The vaccinees were followed from 4 to 48 months. No evidence of long-lasting reactions to the HB vaccine or auto-immunity was observed. 91% of the staff members sero-converted for anti-HBs; none of them showed clinical, biologic or serologic signs of active HB infection; 62% of the hemodialysis patients sero-converted for anti-HBs; none of them became HBs Ag chronic carrier. These results were obtained despite the fact that the prevalence of HBs Ag chronic carriers was 32.7% when the study began. Active immunization proved to be a safer and efficient method to prevent HB infection in a hemodialysis unit.