Optimisation of reconstruction, volumetry and dosimetry for 99mTc-SPECT and 90Y-PET images: Towards reliable dose-volume histograms for selective internal radiation therapy with 90Y-microspheres.

PURPOSE: In Selective Internal Radiation Therapy (SIRT), 99mTc-MAA SPECT images are commonly used to predict microspheres distribution but recent works used 90Y-microspheres PET images. Nevertheless, evaluation of the predictive power of 99mTc-MAA has been hampered by the lack of reliable comparisons between 99mTc-SPECT and 90Y-PET images. Our aim was to determine the "in situ" optimisation procedure in order to reliably compare 99mTc-SPECT and 90Y-PET images and achieve optimal personal dosimetry. METHODS: We acquired 99mTc-SPECT/CT and 90Y-PET/CT images of NEMA and Jaszczak phantoms. We found the best reconstruction parameters for quantification and for volume estimations. We determined adaptive threshold curves on the volumetric reconstruction. We copied the optimised volumes on the quantitative reconstruction, named here the "cross volumes" technique. Finally, we compared 99mTc-SPECT and 90Y-PET Dose Volume Histograms. RESULTS: Our "in situ" optimisation procedure decreased errors on volumes and quantification (from -44.2% and -15.8% to -3.4% and -3.28%, respectively, for the 26.5mL PET phantom sphere). Moreover, 99mTc-SPECT and 90Y-PET DVHs were equivalent only after the optimisation procedure (difference in mean dose <5% for the three biggest spheres). CONCLUSIONS: This work showed that a preliminary "in situ" phantom study was necessary to optimise volumes and quantification of 99mTc-SPECT and 90Y-PET images and allowed to achieve a reliable comparison between patient treatment planning and post implant dosimetry, notably by the use of the "cross volumes" technique. Methodology developed in this work will enable robust evaluations of the predictive power of 99mTc-SPECT, as well as dose-response relationship and side effects in SIRT treatments.

Liver Selective Internal Radiation Therapy with (90)Y resin microspheres: comparison between pre-treatment activity calculation methods.

Different methods to calculate (90)Y resin microspheres activity for Selective Internal Radiation Therapy (SIRT) were compared. Such comparison is not yet available and is needed in clinical practice to optimize patient specific treatment planning. 32 (99m)Tc-macroagregates (MAA) evaluations were performed, followed by 26 treatments. Four methods to calculate (90)Y-activity were applied retrospectively: three based on Body Surface Area and one based on MIRD formalism, partition model (PM). Relationships between calculated activities, lung breakthrough (LB), the activity concentration ratio between lesions and healthy liver (T/N) and tumour involvement were investigated, where lobar and whole liver treatments were analysed separately. Without attenuation correction, overestimation of LB was 65%. In any case, the estimated lungs' doses remained below 30 Gy. Thus, the maximal injectable activity (MIA) is not limited by lungs' irradiation. Moreover, LB was not significantly related to T/N, neither to tumour involvement nor radiochemical purity (RP). Differences in calculated activity with the four methods were extremely large, in particular they were greater between BSA-based and PM activities for lobar treatments (from -85% to 417%) compared to whole liver treatments (from -49% to 61%). Two values of T/N ratio were identified as thresholds: for BSA-based methods, healthy liver doses are much higher than 30 Gy when T/N < 3; for PM, tumour doses are higher than 120 Gy when T/N > 4. As PM accounts for uptake ratio between normal and tumour liver, this method should be employed over BSA-based methods.

Right colonic diverticulitis: an uncommon disease in western countries.

BACKGROUND AND AIMS: Right colonic diverticulitis is not a frequent disease and its management is still controversial. In this study we describe our experience. MATERIAL AND METHODS: We retrospectively reviewed all patients operated on because of a right colonic diverticulitis in our surgical unit. All patients were treated laparoscopically. Demographics, diagnostic and surgical results were recorded. RESULTS: Between January 1994 and January 2007, 11 patients (7 males and 4 females) mean age 53 +/- 9 years (range 39-68), ASA 1: 6 patients, ASA 2: 4 patients, ASA 3: one patient, and BMI 27.8 (range 25-31), had right colonic diverticulitis. Four patients underwent emergency operations: one for peritonitis and three with an erroneous diagnosis of acute appendicitis; seven were operated on electively. There were no deaths or complications. The mean postoperative hospital stay was 5.6 days (range, 3-9). After a mean follow-up of 6.3 years (range 1-13) all patients of this series are symptom-free. INTERPRETATION AND CONCLUSION: Right colon diverticulitis diagnosis remains difficult. A pre-operative imaging screening is necessary to successfully face this challenging disease. Laparoscopy is a safe and effective method to treat these patients. Colectomy should be considered a good therapeutic option for right colonic diverticulitis, although a conservative approach could be proposed in selected cases.

Retention mechanism of peptides on a stationary phase embedded with a quaternary ammonium group: a liquid chromatography study.

We investigated the mechanisms involved in the retention of various peptides on a stationary phase embedded with a quaternary ammonium group (BS C23), by high-performance liquid chromatography. This was compared with peptide retention on a conventional reversed-phase C18 (RP C18) column under isocratic conditions, to understand better the various mechanisms involved. Chromatographic characterization of the two stationary phases with "model" compounds showed that BS C23 is less hydrophobic than RP C18 and induces electrostatic interaction (attraction or repulsion) with ionized compounds. If reversed-phase partitioning was the predominant retention phenomenon, for both stationary phases, the retention mechanisms in BS C23 provided different selectivity to that of RP C18. Electrostatic attraction or repulsion was clearly observed between peptides and the permanent positively charged group embedded in BS C23 depending on the pH. For most of the peptides, a weak anion-exchange mechanism was observed on the quaternary ammonium-embedded stationary phase if mobile phases at neutral pH and low ionic strengths were employed.

Elective versus urgent laparoscopic appendectomy for complicated appendicitis.

AIM: Urgent appendectomy in patients with acute appendicitis (AA) complicated by abscess or phlegmon is associated with a high rate of complications. Recent developments in CT scanning have allowed patients with complicated appendicitis to be better identified. We choose to treat these patients with initial antibiotic therapy followed by elective appendectomy. We reported the results of this strategy and compared it with urgent appendectomy. METHODS: A retrospective analysis of patients diagnosed with complicated acute appendicitis (CAA) between 1998 and 2007 treated either by urgent appendectomy or with antibiotic therapy and elective appendectomy was performed. We assessed the efficacy of antibiotic therapy for CAA. We compared the postoperative course between urgent and elective appendectomy. RESULTS: We treated 56 patients with CAA: 40 by urgent appendectomy and 16 by antibiotics. All 16 patients improved with no need for urgent surgery, with 15 undergoing elective appendectomy. Postoperative complications were significantly lower in the elective group. Conversion rate and mean operative time were also lower but not significantly different. However, the duration of total hospital stay, antibiotic therapy and sick leave were higher. CONCLUSIONS: Initial antibiotic therapy followed by elective appendectomy may be proposed in patients diagnosed with CAA.

Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease.

Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34(+) adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long-term follow-up of these patients. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12-18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long-term follow-up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin increased only at 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.

Chromatographic behaviour of peptides on a mixed-mode stationary phase with an embedded charged group by capillary electrochromatography and high-performance liquid chromatography.

Retention behaviour of biological peptides was investigated on a stationary phase bearing an embedded quaternary ammonium group in a C21 alkyl chain by both high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC). In HPLC experiments, variation of acetonitrile (ACN) content in the mobile phase showed that peptides are mainly separated by RP mechanism. The weak or negative retention factors observed as compared to C18 silica stationary phase suggested the involvement of an electrostatic repulsion phenomenon in acidic conditions. Comparison of HPLC and CEC studies indicated that (i) ion-exclusion phenomenon is more pronounced in HPLC and (ii) higher ACN percentage in mobile phase induce for some peptides an increase of retention in CEC, pointing out the existence of mechanisms of retention other than partitioning mainly involved in chromatographic process. This comparative study demonstrated the critical role of electric field on peptide retention in CEC and supports the solvatation model of hydrolytic pillow proposed by Szumski and Buszewski for CEC using mixed mode stationary phase in CEC.

Altered emotional and locomotor responses in mice deficient in the transcription factor CREM.

Various transcription factors act as nuclear effectors of the cAMP-dependent signaling pathway. These are the products of three genes in the mouse, CREB, CRE modulator (CREM), and ATF-1. CREM proteins are thought to play important roles within the hypothalamic-pituitary axis and in the control of rhythmic functions in the pineal gland. We have generated CREM-mutant mice and investigated their response in a variety of behavioral tests. CREM-null mice show a drastic increase in locomotion. In contrast to normal mice, the CREM-deficient mice show equal locomotor activity during the circadian cycle. The anatomy of the hypothalamic suprachiasmatic nuclei, the center of the endogenous pacemaker, is normal in mutant mice. Remarkably, CREM mutant mice also elicit a different emotional state, revealed by a lower anxiety in two different behavioral models, but they preserve the conditioned reactiveness to stress. These results demonstrate the high degree of functional specificity of each cAMP-responsive transcription factor in behavioral control.

Laparoscopic cystogastrostomy for pancreatic pseudocyst is safe and effective.

Between March 1997 and March 1998, three consecutive patients underwent laparoscopic cystogastrostomy for persistent giant retrogastric pancreatic pseudocyst complicating an attack of acute pancreatitis. The mean cyst diameter was 15 +/- 1 cm (range 14-16). The procedure was performed with four trocars. The anterior wall of the stomach was opened longitudinally. The pseudocyst was entered through the posterior wall of the stomach. A cystogastrostomy was created by suturing the margins of the communication by interrupted nonabsorbable sutures. The mean operative time was 123 +/- 15 min, and there were no postoperative complications. The mean postoperative hospital stay was 4 +/- 1 days. Computed tomography demonstrated complete resolution of the pseudocyst. Laparoscopic cystogastrostomy represents a good therapeutic option for persistent retrogastric pancreatic pseudocyst.

[Laparoscopic cholecystectomy in acute cholecystitis]. / Cholécystectomie laparoscopique dans les cholécystites aiguës.

PURPOSE: To determine the feasibility, operative risk and patients' benefit of laparoscopy in emergency cholecystectomy for acute calculous cholecystitis. PATIENTS AND METHODS: From January 1991 to December 1998, 234 patients with acute calculous cholecystitis were operated on by emergency laparoscopic cholecystectomy. There were 131 women and 103 men (mean age: 57 years), (Asa 2: 48%, Asa 3: 10%). In seven patients, choledocolithiasis was detected by endoscopic ultrasonography and preoperatively treated by endoscopic sphincterotomy. The mean delay between in-hospital admission and cholecystectomy was 20 hours (2-160). Cholecystectomy was performed with primary approach of Calot's triangle. Intraoperative cholangiography, selectively performed (n = 70), detected choledocolithiasis in three patients. RESULTS: The mean duration of surgery was 149 minutes (62-313). The conversion rate was 13% and decreased through the years. The postoperative complication rate was 18%. Eight patients (3.4%) had an abdominal complication. One patient (0.4%) died of bile peritonitis after intraoperative undetected main bile duct injury. The mean postoperative hospital stay was 6.04 days. It was 3.5 days only, very old patients and those with severe associated disease being excluded. CONCLUSION: Laparoscopy appears to be a good approach for emergency cholecystectomy in patients with acute calculous cholecystitis.

Elective laparoscopic sigmoid colectomy for diverticulitis. Results of a prospective study.

BACKGROUND: We undertook a prospective evaluation of elective laparoscopic sigmoid colectomy for diverticulitis in order to assess the risks and benefits of this approach. METHODS: Between November 1992 and November 1996, 54 consecutive patients were included in this study. Their mean age was 59 +/- 13 years (range, 36-81). The number of attacks of diverticulitis before colectomy ranged from one to four (mean, 2.2 +/- 0.7). The operative technique consisted of elective division of the inferior mesenteric vessels, left colonic flexure mobilization, and colorectal anastomosis using the cross-stapling technique. RESULTS: Five procedures (9.2%) were converted. The primary cause for conversion was obesity. These patients had a simple postoperative course. There were no postoperative deaths. Three patients (6.1%) developed abdominal complications, and four patients (8.2%) had abdominal wall complications. Postoperative paralytic ileus lasted only 2.3 +/- 0.7 days (range, 1-6), allowing for a rapid reintroduction of regular diet. The mean postoperative hospital stay was 6.4 +/- 2.7 days (range, 4-15). CONCLUSIONS: Elective laparoscopic colectomy for diverticulitis is feasible in most cases. In most cases, the operative risk is low and the postoperative course is uneventful. Elective sigmoid laparoscopic colectomy should be considered a good therapeutic option for symptomatic diverticulitis.

[Liver resection in patients with polycystic liver disease]. / Résection hépatique chez les malades atteints de polykystose hépatique.

OBJECTIVES: Polycystic liver disease is sometimes responsible for chronic symptoms linked to hepatomegaly which can result in acute complications such hemorrhage or infection of cysts. The aim of this retrospective study was to evaluate the results of partial hepatic resection in patients with symptomatic or complicated polycystic liver disease. METHODS: Twelve patients (11 women and one man, mean age 49) with diffuse polycystic liver disease were treated by partial liver resection (left lateral lobectomy in 7, left hepatectomy in 4, and extended right hepatectomy in 1). Four patients had terminal renal failures and three had chronic haemodialysis. Median follow-up was 34 months. RESULTS: Ascites occurred postoperatively in 10 patients (83%) and was long-lasting (> 2 weeks) in 5; all patients with end-stage renal failure had long-lasting ascites. One of them died on the 40th postoperative day of ascites infection. Another patient with end-stage renal failure died two years postoperatively from chronic disabling ascites and malnutrition while awaiting kidney transplantation. The 10 other patients were markedly improved after partial liver resection, including a marked decrease in hepatomegaly, and the disappearance of chronic symptoms and cystic complications. This beneficial effect was incomplete in the two surviving patients with end-stage renal failure until kidney transplantation was performed. CONCLUSION: These results suggest that partial liver resection is a highly effective treatment in patients with symptomatic polycystic liver disease, preferably before the onset of end-stage renal failure.

[Results of laparoscopic treatment of abdominal emergencies]. / Résultats du traitement coelioscopique des urgences abdominales.

The purpose of this retrospective study was to evaluate the results of the laparoscopic surgical treatment of abdominal emergencies. From May 1991 to September 1995, 200 patients operated by laparoscopy for an acute abdomen were included in this study. The decision to treat the patient by laparoscopy was taken by the surgeon on duty. There were 101 males and 99 females with a mean age of 41 +/- 20 years (range 11-90 years). The main indications for operation were: acute appendicitis (109 patients), acute cholecystitis (52 patients), small bowel obstruction (14 patients) and perforated duodenal ulcer (14 patients). There was no hospital mortality. One per cent of patients experienced an operative complication which was treated by laparotomy. Conversion to laparotomy was needed in 13% of cases. The morbidity rate was 9% and reoperation by laparotomy for acute generalized peritonitis secondary to small bowel perforation was necessary in two cases. Mean postoperative hospital stay ranged from 4 to 7 days. The authors conclude that surgical laparoscopic treatment of the common abdominal emergencies is safe. The conversion rate is low as is the complication rate. These conclusions should be confirmed by a prospective study.

[Treatment of hepatic recurrence after resection of hepatocellular carcinomas]. / Traitement des récidives hépatiques après résection des carcinomes hépatocellulaires.

Between October 1990 and December 1995, 86 patients underwent hepatic resection for hepatocellular carcinoma (HCC). All resections were carried out with the aim of achieving complete cure. Fifty one (60%) of these patients subsequently developed recurrent HCC. Only twenty patients could be treated in our hospital. There were 18 men and 2 women, with a mean age of 61 years at the time of recurrence. Six patients had a normal liver. Fourteen patients had associated liver cirrhosis. using Pugh's classification, 7 patients were Pugh A, 6 Pugh B and 1 Pugh C. The initial hepatic resection had consisted of major hepatectomy in 9 cases and segmentectomy in the remaining 11 patients. The mean time to recurrence was 17 months. There were 3 recurrences on the resection margin and 17 recurrences away from the hepatic stump. The therapeutic choice after hepatic recurrence was based on the number of tumors, hepatic function and the size of the liver remnant. Six patients were treated by tamoxifen due to poor hepatic function; median survival after recurrence was 6 months. Four patients with a single recurrent tumor on an atrophied liver remnant were treated by percutaneous ethanol injection with a median survival after recurrence of 15 months. Five patients with multiple diffuse lesions and good hepatic function were treated by transarterial chemoembolisation with a median survival after recurrence of 30 months. Five patients with a solitary tumor and good hepatic function underwent a second hepatic resection with a median survival after recurrence of 35 months. The overall median survival after diagnosis of recurrence was 20 months. These results suggest that an active treatment should be carried out in cases of recurrence of HCC. A second resection, if technically possible, offers the best chance of survival.

Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol.

Tolerance and dependence induced by chronic delta-9-tetrahydrocannabinol (THC) administration were investigated in mice. The effects on body weight, analgesia and hypothermia were measured during 6 days of treatment (10 or 20 mg kg(-1) THC twice daily). A rapid tolerance to the acute effects was observed from the second THC administration. The selective CB-1 receptor antagonist SR 141716A (10 mg kg(-1)) was administered at the end of the treatment, and somatic and vegetative manifestations of abstinence were evaluated. SR 141716A administration precipitated several somatic signs that included wet dog shakes, frontpaw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, decreased locomotor activity and mastication, which can be interpreted as being part of a withdrawal syndrome. Brains were removed immediately after the behavioural measures and assayed for adenylyl cyclase activity. An increase in basal, forskolin and calcium/calmodulin stimulated adenylyl cyclase activities was specifically observed in the cerebellum of these mice. The motivational effects of THC administration and withdrawal were evaluated by using the place conditioning paradigm. No conditioned change in preference to withdrawal associated environment was observed. In contrast, a conditioned place aversion was produced by the repeated pairing of THC (20 mg kg(-1)), without observing place preference at any of the doses used. This study constitutes a clear behavioural and biochemical model of physical THC withdrawal with no motivational aversive consequences. This model permits an easy quantification of THC abstinence in mice and can be useful for the elucidation of the molecular mechanisms involved in cannabinoid dependence.

CCK-B receptors in the limbic system modulate the antidepressant-like effects induced by endogenous enkephalins.

Systemic administration of RB 101, a complete inhibitor of enkephalin catabolism, has been reported to induce antidepressant-like responses in mice which were potentiated by an ineffective dose of a CCK-B antagonist. The aim of this study was to investigate the neuroanatomical substrate involved in the facilitatory effects induced by CCK-B antagonists on RB 101 behavioural responses. Thus, the CCK-B antagonist PD-134,308 was locally administered into different brain structures (anterior nucleus accumbens, central amygdala and caudate nucleus) and its effects on the antidepressant-like response induced by systemic administration of RB 101 were evaluated in the conditioned suppression of motility (CSM) test in rats. RB 101 administered alone by the IV route decreased the CSM in rats, as previously obtained in mice. Systemic administration of a non effective dose of PD-134,308 facilitated the antidepressant-like effect induced by RB 101. Local injection of PD-134,308 into the anterior nucleus accumbens, the central amygdala or the caudate nucleus did not modify CSM. The antidepressant-like effects elicited by RB 101 in this test were potentiated by PD-134,308 after microinjection in the anterior nucleus accumbens and central amygdala, but not in the caudate nucleus. All these effects were observed only in shocked animals. The present results suggest that the mesolimbic system, particularly the anterior nucleus accumbens and the central amygdala, seems to play an important role in the interaction occurring between the endogenous CCK and opioid system in the control of behavioural responses.

Aprotinin reduces blood loss in patients undergoing elective liver resection.

Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision.

Preoperative predictors of blood transfusion in liver resection for tumor.

BACKGROUND: Hepatic resection remains a hemorrhagic procedure. The purpose of this study was to investigate the preoperative predictive factors of intraoperative blood transfusion. METHODS: One hundred consecutive patients who underwent hepatic resection for tumor were included in this retrospective study. Resection was performed for primary malignancies (n = 52), metastases (n = 18), and benign tumors (n = 30). Liver resection was performed under intermittent clamping of the portal triad. Seventeen variables were analyzed. RESULTS: The operative blood loss was 1,872 mL (mean 1,104; range 650 to 4500) for the 22 transfused patients. The mean blood transfusion was 5.5 units (mean 3.2; range 2 to 12) of packed red cells. Multivariate analysis demonstrated that the size of liver resection (P <0.001) and the prothrombin rate (P <0.001) were independently correlated with blood transfusion. CONCLUSIONS: Patients undergoing extended resection or with abnormal coagulation could be considered for autologous blood transfusion.