Assisted hepatic resection using a toroidal HIFU device: an in vivo comparative study in pig.

PURPOSE: Bleeding is the main cause of postoperative complications during hepatic surgery. Blood loss and transfusions increase tumor recurrence in liver metastases from colorectal cancer. A high intensity focused ultrasound (HIFU) device with an integrated ultrasound imaging probe was developed for the treatment of colorectal liver metastasis. METHODS: The HIFU toroidal-shaped transducer contains 256 elements (working frequency: 3 MHz) and can create a single conical lesion of 7 cm3 in 40 s. Then, the volume of treatment can be significantly increased by juxtaposing single lesions. Presented here is the use of this device in an animal model as a complementary tool to improve surgical resection in the liver. Before transecting the liver, a wall of coagulative necrosis was performed using this device in order to minimize blood loss and dissection time during hepatectomy. Resection assisted by HIFU was compared to classical dissections with clamping [intermittent Pringle maneuver (IPM) group] and without clamping (control group). For each technique, 14 partial liver resections were performed in seven pigs. Blood loss per dissection surface area and resection time were the main outcome parameters. RESULTS: Conserving liver blood inflow during hepatic resection assisted by HIFU did not increase total blood loss (7.4 +/- 3.3 ml cm(-2)) compared to hepatic resection performed during IPM and controlled blood inflow (11.2 +/- 2.2 ml cm(-2)). Lower blood loss was measured on average when using HIFU, even though difference with clamping (IPM) was not statistically significant (p = 0.09). Resection assisted by HIFU reduced blood loss by 50% compared to control group (14.0 +/- 3.4 ml cm(-2), p = 0.03). The duration of transection when using HIFU (13 +/- 3 min) was significantly lower compared to clamping (23 +/- 4 min, p < 0.01) and control (18 +/- 3 min, p = 0.02). Precoagulation also resulted in sealing blood vessels with a diameter of less than 5 mm, and therefore the number of clips needed in the HIFU group was significantly lower (0.8 +/- 0.2 cm(-2)) when compared to clamping (1.6 +/- 0.2 cm(-2), p < 0.01) and control (1.8 +/- 0.4 cm(-2), p < 0.01). CONCLUSIONS: This method holds promise for future clinical applications in resection of liver metastases.

The prognostic role of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma: experience of the Genoa group.

AIM: To define the benefit of intraoperative frozen section examination of the sentinel lymph node (sN), and to assess its prognostic value in clinically node-negative melanoma patients. MATERIALS AND METHODS: Between July 1993 and December 2001, 214 patients with Stage I-II cutaneous melanoma underwent sN biopsy; complete follow-up data are available in 169 of 175 patients who underwent preoperative lymphoscintigraphy, lymphatic mapping with Patent Blue-V and radio-guided surgery (RGS). RESULTS: In an initial subset, the sN was identified in 35 out of 39 patients; in the principal group of 169 patients, the sN was detected in all patients. The benefit of frozen section examination, that is the proportion of all patients having intraoperative histologic examination who tested positive, was 17.2% (29/169); notably, in patients with pT(1-2) vs pT(3-4) melanoma the corresponding values were 2.3 and 33.3%, respectively, (P=0.000). Cox regression analysis for overall survival indicated that sN-positive patients had a two-fold increased risk of death; the most significant predictors of relapse-free survival were sN status (P=0.004), age (P=0.015), and T stage grouping (P=0.033). CONCLUSIONS: The sN is a reliable predictor of regional lymph node status in patients with cutaneous melanoma. Frozen section examination can be useful in avoiding a 'two-stage' operative procedure in patients with tumour-positive sN, but its greatest benefit seems to be restricted to patients with pT(3)-pT(4) primary melanoma.

[Diagnostic protocol of thyroid nodules used in a surgical case series (409 cases)]. / Protocollo diagnostico dei noduli tiroidei utilizzato in una casistica chirurgica (409 casi).

BACKGROUND: The introduction of ultrasonography and fine needle biopsy (FNB) has changed the approach towards thyroid pathology. At the Division of Surgical Oncology of the National Institute for Cancer Research in Genoa we use a complex diagnostic system for the selection of patients affected by thyroid pathologies. Our aim is to analyze this methodology and find the best diagnostic procedure for the individual patient. METHODS: Between January 1982 and June 1997, 2500 patients (pts) were found to be affected by thyroid pathologies. The diagnostic procedures for thyroid pathologies are: physical examination and anamnesis, scintigraphy, ultrasonography, fine needle biopsy, blood dosages, radiography of trachea and aesophagus; some cases require Computerized Tomography of the neck and Magnetic Nuclear Resonance. At the end of the examinations 409 pts underwent surgery; we will be evaluating the diagnostic system of these patients. RESULTS: We found from our data, that the group with the highest incidence of malignant tumors is characterized by a large number of instrumental examinations. In fact, 55/73 pts underwent all the instrumental exams, and in 21.1% a malignant tumor was found. These data are interesting, but more important is that only 409 patients out of 2500 underwent surgery 16.3%. CONCLUSIONS: We believe that one single instrumental examination is not enough to detect the characteristic of a thyroid nodule; the three most important examinations, scintigraphy, ultrasonography and cytology, would make it possible to select those cases which need a surgical approach. We believe that the 20% incidence in these cases can be considered good result, considering that the incidence of malignant tumors in thyroid pathologies is about 5% and that in these cases although the tumors were not malignant, they were operated on for functional or mechanical disorder.

Radioimmunoguided surgery with different iodine-125 radiolabeled monoclonal antibodies in recurrent colorectal cancer.

Sixty-four patients with recurrent or metastatic colorectal cancer underwent radioimmunoguided surgery (RIGS). Thirty patients (Group A) were preoperatively injected with radiolabeled monoclonal antibody (MAb) B72.3, a whole IgG1 that reacts with tumor-associated glycoprotein (TAG-72) antigen. Thirty-four patients (Group B) were given monoclonal antibody FO23C5, an F(ab')2 which reacts with the carcinoembryonic antigen (CEA). The use of F(ab')2 antibodies ensured a lower time interval from the preoperative injection of the radiolabeled MAb to surgery. This interval was 22.7 days for Group A patients and 10.9 days for Group B patients. The correct RIGS identification of tumor sites occurred in 80.4% of Group A patients and in 92.6% of Group B patients. Additional information capable of modifying surgical strategy was obtained in 23.3% of Group A patients and in 8.8% of Group B patients. This difference was due to the different patterns of biodistribution and pharmacokinetics of the two MAbs. Although FO23C5 yields an improved diagnostic resolution for macroscopic tumor sites, we believe that B72.3 or other whole IgG1 should be the first choice for RIGS in recurrent or metastatic colorectal cancer patients.

Role of tumor-associated antigen expression in radioimmunoguided surgery for colorectal and breast cancer.

One hundred thirty-six patients with colorectal and breast cancer were enrolled in a retrospective study using radioimmunoguided surgery (RIGS) with Iodine-125 (I125) radiolabeled B72.3 (Group A, 73 patients) and F023C5 (Group B, 63 patients) monoclonal antibodies (MAbs). The correlation between intraoperative tumor-to-normal tissue (T/NT) gamma-detecting probe (GDP) counts ratio and the expression of tumor-associated glycoprotein (TAG)-72 (GroupA patients) and carcinoembryonic antigen (CEA; Group B patients) tumor-associated antigens (TAA) expression of 209 resected or biopsy tumor specimens was assessed. Ex vivo radioimmunolocalization index (R.I.) was carried out on the same specimens as a control of intraoperative GDP ratio values. RIGS positive definition of tumor occurred in 80/113 (70.8%) tumor sites of Group A patients and in 84/96 (87.5%) tumor sites of Group B patients. Mean percent B72.3 TAA expression of 113 tumor sites of Group A patients was 62.74 +/- 28.79% vs. 73.00 +/- 26.28% of 96 tumor sites of Group B patients (P < 0.05). The higher incidence of positive RIGS results was observed in tumor sites with the higher expression of the relative TAA. A statistically significant correlation between RIGS ratios and B72.3 and CEA expression was observed in the 113 tumor sites of Group A (P < 0.05) and in the 96 tumor sites of Group B (P < 0.01), respectively. The role of a preoperative evaluation of TAA expression in patients undergoing RIGS is discussed. Its assessment, whenever possible, may help to select those patients who will benefit more from this immunodiagnostic technique.

Influence of dietary habits on thyroid status of a nomadic people, the Bororo shepherds, roaming a central African region affected by severe iodine deficiency.

OBJECTIVE: In contrast with the endemic goiter reported in several African countries, the nomadic Bororos of the Central African Republic have an unexpectedly low prevalence of goiter. This study was conducted to elucidate this puzzling observation. DESIGN: Thyroid function and iodine and thiocyanate intakes were evaluated in Bororos and inhabitants of the same area and compared with an Italian population. RESULTS: Urinary iodine concentrations indicated moderate iodine deficiency in the rural people and the Bororos. In the latter, no individual with clinical hypothyroidism was observed. Compared with the reference population, the Bororos had slightly lower thyroxine (T4) and free thyroxine (FT4), slightly increased tri-iodothyronine (T3) and T3/T4 ratio, slightly higher TSH, normal serum thyroglobulin, a prevalence of goiter of 17.1% and a higher urinary thiocyanate. The rural people showed striking differences: lower T4 and FT4, increased T3/T4 ratio, markedly increased TSH and thyroglobulin, a prevalence of goiter of 76.9% and a high urinary thiocyanate, indicating frequent consumption of cassava. A dietary survey indicated that the Bororos ingest large amounts of milk and related products but infrequently eat cassava. CONCLUSION: A minute difference in iodine deficiency between two populations induces totally different patterns of goiter and thyroid function. The reason for such a contrast probably involves differences in diet.

[Non-toxic nodular goiter: treatment and follow-up]. / Trattamento e follow-up del gozzo non tossico uni o multinodulare.

Between 1982 and 1993, 224 patients (196 females and 28 males) with benign lesion of the thyroid underwent surgery. This group included: 1) 210 pts with p multinodular goiter or solitary nodule with normal serum levels of T3, T4, FT3, FT4, TSH (Thyroid stimulating hormone; 2) 14 pts with a hyper-functioning goiter; 3) 12 pts with recurrent nodules following surgery which had been carried out in another hospital. In this study only those pts with solid cold (hypofunctioning) nodules which had not been treated previously were evaluated. The minimal follow-up was 18 months. It consisted of serologic studies (86 cases), ultrasonography (70 cases) and ultrasonography and scintigraphy (5 cases). We performed isthmusectomy in 2 cases, total lobectomy in 42 cases and subtotal thyroidectomy in 42 cases. Out of the 86 pts evaluated, 70 (81.3%) were treated with post-surgical hormone suppressive therapy (Levothyroxin 100 gamma daily). The endogenous thyroid stimulating hormone (TSH) was suppressed in 50 cases (71%), while 20 pts (28.5%) remained within the norm. Thyroid ultrasonography demonstrated recurrent nodules in 14 out of the 86 evaluated (16.2%). All these pts received thyroxine therapy. Among the 50 pts who had been treated with an adequate dose of thyroid hormone, 5 had recurrences (10%), as compared to 3 out of the 20 cases (15%) who had been administered thyroxine dosage not high enough to suppress THS and to 6 pts out of the 16 (33.5%) who had not been administered thyroid hormone. One out of the 20 pts (5%) who had undergone total lobectomy and post-surgical suppressive hormone therapy developed recurrence as compared to 6 out of the 24 pts (25%) who had under gone lobectomy and had been administered a hormone dosage which was not high enough to suppress TSH. Four out of the cases (13.3%) who had under gone subtotal thyroidectomy and post-surgical suppressive hormone therapy had recurrence as compared to 3 out of the 12 (25%) who had undergone subtotal thyroidectomy without TSH suppression. We conclude that treatment with thyroid hormone decreases the risk of benign recurrences only when undergone a long thyroxine therapy in doses high enough to suppress endogenous TSH.

Role of B72.3 iodine 125-labeled monoclonal antibody in colorectal cancer detection by radioimmunoguided surgery.

BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal antibodies and a probe has been reported to be useful in recognizing subclinical tumor deposits during operation. Aim of this study was to understand the limits of this technique and to assess the potential diagnostic use of RIGS in colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG 72 antigen, labeled with iodine 125, was injected in 32 patients with primary tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty-three suspected tumor sites were evaluated during operation by means of probe and resected with immunohistochemistry as control. RESULTS: Primary tumor sites were localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of cases. There was a significant correlation both for primary (p < 0.001) and recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72 tumor antigen expression. Results obtained with the probe were instrumental in modifying the surgical approach in six (27%) of 22 patients with recurrences, allowing the removal of tumor masses that would otherwise have been overlooked. CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical use. The potential high diagnostic resolution appears to improve surgical ablation of colorectal cancer, especially in patients with recurrent cancer or suspected recurrent tumors who have negative results for intraabdominal disease by all other roentgenographic criteria with rising carcinoembryonic antigen or TAG 72 antigen levels.

[Biliary surgery and cholescintigraphy with iminodiacetic acid (IDA) analogs. An evaluation of the results and the complications]. / Chirurgia biliare e colescintigrafia con analoghi dell'acido iminodiacetico (IDA). Valutazione dei risultati e complicanze.

Hepatobiliary scintigraphy with analogs of iminodiacetic acid (IDA) has become one of the primary tools in the diagnosis of biliary tract diseases, especially in the evaluation of surgical results and detection of complications that may arise from biliary operative procedures. We have performed cholescintigraphy in 19 patients. Of them, 9 underwent choledochojejunostomy with Roux-en-Y reconstruction for recurrent choledocholithiasis, 1 underwent right hepatic resection for metastasis extirpation, 8 were post cholecystectomy patients effected with upper abdominal pain located either in the epigastric region or right upper quadrant referable to post cholecystectomy syndrome and the last exhibited chronic pancreatitis ans suspicious sphincter of Oddi stenosis. The scintigraphy data were compared with the information yielded by sonography, intravenous cholangiogram (IVC) and, when possible, by endoscopic retrograde cholangiopancreatography (ERCP). Scans were considered pathologic when one or more of the following criteria were present: a) delayed biliary to bowel transit (greater than 1 hr), b) abnormal time-activity dynamic, c) no intestinal activity (obstruction), d) apparent ductal dilatation. In the group of biliary-enteric anastomosed patients, cholescintigraphic findings have shown 3 normal cases, 3 cases of biliary-intestinal obstruction confirmed by surgery, and 3 with abnormal activity retention in the jejunum loop due, in 2 patients, to hypokinesia since the quick emptying following the administration of 10 mg i.v. of metoclopramide, while in the other one, the surgery reexploration exhibited the presence of adhesions producing intestinal stricture. in the last patient of this group, the cholescintigraphy was performed to detect possible biliary leaks. In the post cholecystectomy patients, the cholescintigraphy exhibited in 3 cases dilated common duct with functional patency since the normal biliary-bowel transit time (less than 1 hr); this was confirmed by sonogram and IVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonographic evaluation of local recurrences of soft tissue sarcomas.

The aim of our study was to establish whether ultrasonography can be proposed as the main diagnostic technique for the follow-up of soft tissue sarcoma (STS). In 26 patients with previous history of STS, a sonographic examination was carried out using a 5 MHz linear transducer to identify early local recurrences. Sonography was performed every 3 months and a computed tomographic (CT) control was made when the sonogram showed findings strongly suggestive of recurrence. STS recurrences were detected by sonography in 20 of 26 patients (77%) and were confirmed by histologic examination. In six cases, sonographic results were uncertain and in three of these the recurrence was ascertained by biopsy. CT scan provided a correct diagnosis in 16 patients (61.5%) and only in cases with lesions greater than 5 cm in diameter. From our experience we conclude that high frequency sonography is a most accurate noninvasive approach in early detection of STS recurrences. CT plays an important role in the cases amenable to surgery treatment and is recommended to obtain a better assessment of anatomic connection between tumor and adjacent structures.

Potentiation of topoisomerase I and II inhibitors cell killing by tumor necrosis factor: relationship to DNA strand breakage formation.

Recombinant human tumor necrosis factor (rHuTNF) synergistically potentiates the cytotoxicity of the topoisomerase I inhibitor camptothecin, and the topoisomerase II inhibitors epidoxorubicin, etoposide, mitoxantrone, ellipticine, actinomycin D and 4'-(9-acridinylamino)methanesulfon-m-anisidide on A2780 human ovarian cancer cell line. Similar synergy was not observed with a combination of rHuTNF and cis-platinum or mitomycin C. When A2780 cells were incubated with rHuTNF simultaneously with camptothecin or mitoxantrone or VP16, increased numbers of DNA single-strand breaks were produced. rHuTNF alone did not induce DNA strand breakage. These data provide evidence that the enhancing effect of rHuTNF is closely related to the DNA damage mediated by topoisomerase-targeted drugs. These observations may have relevance for ovarian cancer treatment.

Hormonal and biochemical patterns in subjects from a new endemic goiter area in the Central African Republic.

Hormonal serum patterns of 268 subjects, living in rural villages and in the chief town of the Ouham province (Bocaranga), were studied to accomplish a survey in this endemic goiter area of the Central African Republic (CAR). Circulating TSH, TT3, TT4, FT4, rT3 and TG were determined in an accurately randomized population sample. Urinary excretion of iodine and thiocyanate (SCN) was also measured. The comparison of the mean values of such parameters with control values showed statistically significant differences (P < or = 0.05 divided by 0.001) in all the parameters studied, excepting TT3. The urinary iodine excretion was lower than 35 micrograms/l in the chief town and of 25 micrograms/l in the rural villages. The thiocyanate excretion was constantly greater than 8 mg/l; the I/SCN ratio = 3.7 was clearly lower than in controls. In a sample of 41 subjects, whose hormonal patterns were in the physiological range, significant differences were found between their TT3, TT4, FT4, TSH and TG serum concentrations and the respective control values. The severe iodine deficiency and the high consumption of manioc as a staple food are the prominent etiopathogenic factors of the hyper endemic goiter in this region. The authors believe that extensive iodoprophylactic action is urgently needed.

Ouham-Pendé: a new endemic goiter area in the Centroafrican Republic (CAR): epidemiological survey on 7621 subjects.

The authors report epidemiological observations about a new endemic goiter area in the North western region of the Centro-African Republic (CAR). The research was carried out in 7 quarters of the chief-town (Bocaranga) and in 8 rural villages; 7621 people were examined by the same three of the present Authors who filled in a sample individual form (proposed by WHO) with the generalities and the goiter grading. The data were analyzed according to sex, age and place of residence by means of the common position parameters and the cumulative frequencies, taking into account the goiter grading of each group. The goiter prevalences observed in the rural areas varied from 70.9% (males) to 82.6% (females), whereas in the chief-town they varied from 29.3% (males) to 57.9% (females). Neurological and myxedematous cretins were seen to constitute 3.4% of the visited population. The M/F goitrous ratio was near unity under the age of 6; above this age, females are more widely and severely affected than males. An important fall in goiter prevalence was observed in adult males after the age of 16. The gradings observed in the rural villages, in both females and males of different ages (0-5; 6-15; 16-45; greater than 45 ys.) were significantly more severe than those observed in the chief town (P less than 0.01). The results obtained confirm those of a preliminary survey which the Authors previously carried out on a sample of school children living in the same region of CAR.

Ouham-Pendè: a new endemic goiter area in Centro-African Republic (C.A.R.). Preliminary observations on school children.

In this work, the Authors make several epidemiological observations and report a series of biohumoral data relative to a new endemic goiter area in the north-western region of the Centro-African Republic (CAR). In this province whose chief-town is Bocaranga, living conditions are very poor and primitive, manioca being the staple food. The survey was carried out in 11 rural schools and in 2 schools in the chief-town; 4009 subjects were examined; 2839 were males, 1170 females. The goiter prevalence observed in the whole sample population was 79.75%. The prevalence for each step of the grading were: 34.6% for 1a; 32.9% for 1b; and 11.8% for 2. In the schools of the chief town the goiter prevalence was found to be significantly lower than in the rural schools (71.9% versus 83.6% with P less than 0.01). Being the goitrous F/M ratio equal to 1.041, the goiter prevalences and gradings in females were higher and more severe than in males. After calculating these differences by means of the cumulated frequencies and the Kolmogorov Smirnov test, they were found to be significant. In 45 goitrous subjects, high TSH (7.19 microU/ml +/- 5.1), T3 (1.65 ng/ml +/- 0.56), and TG serum levels (410 ng/ml +/- 280) were found; however, low normal levels were observed for rT3 (8.97 ng/dl +/- 7.5) and fT4 (0.50 ng/ml +/- 0.51). In 42 casual urine samples, iodine excretion was 23.2 micrograms/l +/- 12.8; thyocianate excretion was 9.72 mg/l +/- 6 with a I/SCN ratio = 2.38.(ABSTRACT TRUNCATED AT 250 WORDS)