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Characteristics at presentation and outcome of hepatocellular carcinoma (HCC) in the elderly. A study of the Cancer of the Liver Italian Program (CLIP).

PURPOSE: To describe the characteristics at presentation and the outcome of elderly patients (> or =70 years old) with HCC, a retrospective analysis using a CLIP database was performed. PATIENTS AND METHODS: The database included 650 patients. Chi2-test, logistic and Cox model were applied. RESULTS: Baseline characteristics and stage were similarly among elderly (n=158) and non-elderly (n=492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p<0.0001). Age and CLIP score were independently predictive of the odds of locoregional treatment. Prognosis was worse for elderly patients with a hazard ratio of death of 1.49 (95% CI 1.20-1.86) at multivariable analysis. The survival difference disappeared when patients were compared within each treatment group, suggesting a close link between undertreatment and shorter survival. CONCLUSION: Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.

Age Factors↗

Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.

The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets are multivariate, and each RBP suffers non-uniform signal-to-noise ratio. To address this, we developed Mudskipper, a versatile computational suite comprising two components: a Dirichlet multinomial mixture model to account for the multivariate nature of ABC datasets and a softmasking approach that identifies and removes non-specific protein-RNA interactions in RBPs with low signal-to-noise ratio. Mudskipper demonstrates superior precision and recall over existing tools on multiplex datasets and supports analysis of repetitive elements and small non-coding RNAs. Our findings unravel splicing outcomes and variant-associated disruptions, enabling higher-throughput investigations into diseases and regulation mediated by RBPs.

RNA-Binding Proteins↗

Outpatient laparoscopic sterilisation: Comparison between electrocautery and clip application.

In a personal prospective series of 504 day-case laparoscopic sterilisations in 1977-78, unipolar tubal electrocoagulation was compared with spring-loaded clip application. Two patients who had cautery required laparotomy because of serious bleeding and one because of accidental bowel diathermy. Clip application was free from serious complications, but caused more post-operative pain. The majority of patients were performing normal or light household duties within 24 hours of sterilisation.

Adult↗

Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.

BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

Carcinoma, Hepatocellular↗

[Experience with the tupla-clip for tubal sterilization by laparoscopy (author's transl)].

For the last 18 months a plastic clip made of polyoxymethylene was used for tubal sterilization by laparoscopy. The clip was used in 140 cases. This report reviews 106 cases. One pregnancy occurred early in this series. There were no other complications. The advantages of the method are the short operating time and the elimination of intra-abdominal damage by heat. Reversibility of the method has not yet been assessed.

Adult↗

[Early and late complications after tubal ligations with the tupla-clip (author's transl)].

Following three years of the use of the tupla-clip we were able to send questionnaires to 115 women. The mean age was 33 years with 2--3 children. 57% of the tubal sterilizations were done for medical reasons, 7% for social reasons and 56% for personal reasons. 15% of the sterilizations were done concommitant to pregnancy. Among 243 tupla-clip sterilizations 2 pregnancies occured as early complications. The 115 women were asked regarding somatic complaints, psychic side effects, and social difficulties. The personal evaluation of this sterilization method was reported as good by 68%, doubtful by 26%, and negative by 6% of the patients. Technically this method of tubal sterilization is secure, fast, and the complication rate is low.

Adolescent↗

The StarClose Vascular Closure System: interventional results from the CLIP study.

BACKGROUND: The StarClose Vascular Closure System is a femoral access site closure technology that uses a flexible nitinol clip to complete a circumferential, extravascular arteriotomy close. The Clip CLosure In Percutaneous Procedures study was initiated to study the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596 subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or standard compression of the arteriotomy after the percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. RESULTS: The results of the diagnostic StarClose cohort have been reported separately. Results for the interventional arm revealed major vascular complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual compression subjects (1/91; P = 1.00). No infections were seen in either cohort. Minor complications in the StarClose interventional group occurred at a rate of 4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or arteriovenous fistula was not seen with StarClose. With StarClose, procedural success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the interventional group. Device success for the treatment group was 86.8%. In the interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not statistically different. CONCLUSIONS: The clinical results of this study demonstrate that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures. StarClose significantly reduced time to hemostasis, ambulation, and dischargeability when compared with compression.

Aged↗

Differential expression of CLIP:MHC class II and conventional endogenous peptide:MHC class II complexes by thymic epithelial cells and peripheral antigen-presenting cells.

Major histocompatibility complex (MHC) class II molecules expressed by thymic epithelial cells are involved in positive selection of CD4 T cells, whereas the high-avidity interaction of T cell receptors with the endogenous peptide: MHC class II complexes expressed on bone marrow (BM)-derived antigen-presenting cells (APC) and, to a lesser extent, on thymic epithelial cells mediate negative selection. To understand better the generation of the CD4 T cell repertoire both in the thymus and in the periphery we analyzed relative levels of expression of specific endogenous peptide: MHC class II complexes in thymic epithelial cells (TEC) and peripheral APC. Expression of E alpha52-68: I-A(b) and class II-associated invariant chain peptide (CLIP): I-A(b) complexes in thymic epithelial cells and in the bone-marrow derived splenic APC, i.e. B cells, was studied using YAe and 30-2 monoclonal antibodies which are specific for the corresponding complexes. To distinguish between expression of both complexes in radioresistant thymic epithelial elements and radiation sensitive BM-derived APC, radiation BM chimeras were constructed. Using immunohistochemical and immunochemical approaches we demonstrated that the level of expression of E alpha52-68: I-A(b) complexes in thymic epithelial cells is approximately 5-10% of that seen in splenic cells whereas total class II levels were comparable. In contrast, CLIP: I-A(b) complexes are expressed at substantially higher levels in TEC vs. splenic APC. This result demonstrates quantitative differences in expression of distinct peptide: MHC class II complexes in thymic epithelial cells and peripheral splenic APC.

Animals↗

Use of an instrument-holding clip for deeply recessed anastomoses of the rectum and esophagus.

Posterior layer closure of deeply located anastomoses including those performed in the course of low anterior rectal resection, total gastrectomy, and esophagogastrectomy, are often difficult. Usually five to six seromuscular or through-and-through posterior wall sutures are inserted sequentially and the loop or cut end of bowel is advanced over these parallel sutures. The sutures are then tied down. Entanglement of these sutures in a deep surgical field with limited access can lead to tears in the bowel wall. In addition, uneven and nonsequential tying of these sutures may compromise the anastomosis itself. We have described here how manual anastomosis in deep, hard to reach surgical fields can be better accomplished with the use of an instrument-holding clip. Use of the described instrument-holding clip, to clearly delineate and anchor each suture in sequence, eliminates these problems. An easily available device, it can save operative time, facilitate a more even anastomosis, and decrease the chance of bowel wall tearing, thus enhancing the security of the anastomosis.

Anastomosis, Surgical↗

Clipping of proximal paraclinoid aneurysms with support of the balloon-catheter "trapping-evacuation" technique. Technical note.

A method is described in which we use a combined endovascular balloon-catheter technique and open microneurosurgical approach for clipping aneurysms of the proximal paraclinoidal intracranial segment of the internal carotid artery. By temporary occlusion of the cervical carotid artery and continuously retrograde sucking of blood from the distal vessel via a double-lumen balloon-catheter, clip application to large and critically located aneurysms is facilitated applying evacuation-decompression to the trapped arterial segment under intra-operative SEP-monitoring.

Adult↗

Management and postoperative mortality related to time of clipping for supratentorial aneurysms: a personal series.

An analysis of all 197 consecutive cases of intracranial aneurysms treated by one of us (B. W.) was carried out. 82% were ruptured anterior circle aneurysms. 144 cases were analyzed with respect to post-operative and management mortality where patients were eligible for definitive clipping. Grade-time interactions on transfer to the neurosurgeon were considered. Early operation was not associated with significantly higher post-operative and management mortality. 116 cases clipped and discharged from hospital had longer follow-ups to see if earlier operation was associated with a poorer neurological and social outcome. This was not the case. We therefore believe that since the prime rationale for surgery following subarachnoid haemorrhage is the prevention of rebleeding and since this is more common immediately following the initial haemorrhage, early surgery is indicated whenever this is technically feasible. Since 1978, with a deliberate policy of trying to operate early, for all grades there has been a post-operative mortality of 3%, a case management mortality of 20% and 87% of patients operated upon have been able to go home.

Constriction↗

Obstructive jaundice from open vessel clip.

Obstructive jaundice occurred 3 years after cholecystectomy in a 49-year-old man. At surgery a large stone was discovered in the common bile duct. Pathologic examination showed that the stone had formed around an open vessel clip. Migration of an open vessel clip to the biliary system with subsequent stone formation has not been reported previously.

Cholestasis↗

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney, one-clip renal hypertension.

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.

Animals↗

Anaesthesia for caesarean section and cerebral aneurysm clipping.

A pregnant patient at 38 weeks gestation presented for a combined procedure of Caesarean section, tubal ligation and cerebral aneurysm clipping. Anaesthesia was induced with thiopental, succinylcholine was administered to facilitate tracheal intubation, and intravenous lidocaine and sodium nitroprusside were used to reduce the hypertensive response to tracheal intubation. Anaesthesia was maintained with nitrous oxide until delivery of the infant, after which time fentanyl, low-dose halothane and pancuronium were added for maintenance of anaesthesia during the neurosurgical procedure. Blood pressure was controlled during the case by administration of a sodium nitroprusside infusion and propranolol. Following completion of the surgical procedures, the patient promptly emerged from anaesthesia and was neurologically normal in the operating room. It is concluded that general anaesthesia can be used satisfactorily for a combined procedure of Caesarean section and cerebral aneurysm clipping.

Adult↗

[The VCS clip--experimental experiences with a new vascular suture stapling device].

Despite improvements in technique and suture material, vascular anastomosis is still associated with a significant rate of early (stenosis, thrombosis) and late (intimal hyperplasia) complications. Although automatic mechanical staplers were practical und comparatively safe to use, they did not play a major role in vascular surgery, probably due to the complexity and difficult handling. In an experimental study with the VCS clip system, we found a significant improvement in performing a hepatic artery anastomosis [9.2 +/- 1.5 min (VCS) vs 20.6 +/- 2.7 min (suture), P < 0.001], early patency and flow rate [150 +/- 29.1 ml/min (1.0 h)-->79.9 +/- 24.0 ml/min (24 h) (suture) vs 186 +/- 45 ml/min (1.0 h)-->162 +/- 48 ml/min (VCS), P < 0.005]. Besides easy handling, the VCS clip system allows for a fast, standardized vascular anastomosis without intimal penetration.

Anastomosis, Surgical↗

Migratory surgical clip in the common bile duct: CT diagnosis.

There are only a few case reports in the literature describing the migration of metallic surgical clips into the common bile duct. Diagnosis of this postcholecystectomy complication is usually made during ERCP. We describe the identification on CT scan of a migratory surgical clip in the common bile duct in a patient with biliary colic.

Aged↗

Colocalization of collagen overexpression and inflammatory cell infiltration in the two-kidney one-clip rat model from the early days of hypertension onward.

In the first 6 days of hypertension, infiltrated mononuclear cells were colocalized with collagen (I) mRNA-overexpressing fibroblasts in the adventitial area of unclipped kidney. The number of adventitial infiltrated mononuclear cells was correlated with adventitial collagen (I) surface expansion. After 22 days of hypertension no collagen (I) mRNA-overexpressing fibroblasts or any increase in collagen area or mononuclear cell infiltration was observed. In the interstitium of unclipped kidney, collagen (I) mRNA overexpression, collagen (I) expansion and mononuclear cell infiltration began later, from the 7th day of hypertension, and kept increasing. In the clipped kidney, after expansion in the first 6 days of hypertension, the adventitial collagen remained stable. These results suggest that in the unclipped kidney fibroblastic activation begins within the first 6 days of hypertension in the adventitial area, but is transient, and fibrosis then spreads in the interstitium. Mononuclear cell infiltration is colocalized and correlated with adventitial and interstitial fibrosis. In the first 6 days, hypertension is not the only cause of fibrosis; the same level of adventitial fibrosis is detected in the nonhypertensive clipped kidney. All observed pathological phenomena could be detected within the first 3 days of hypertension.

Animals↗

Limited endoscopic thoracic sympathetic block for hyperhidrosis of the upper limb: reduction of compensatory sweating by clipping T4.

BACKGROUND: Endoscopic thoracic sympathicotomy of T2 to T4 (ETS 2-4) has evolved into an effective treatment for severe hyperhidrosis of the upper limb. Complications such as bleeding or Horner's syndrome are rare, but side effects such as compensatory and gustatory sweating occur in 30-50% of patients. Following the Lin-Telaranta classification, we aimed to reduce these side-effects by clipping T4 solely [endoscopic thoracic sympathetic block (ESB 4)]. We present our experience and clinical results using this method, with emphasis on patients' quality of life. METHODS: A total of 176 procedures (91 patients) were carried out in the ETS 2-4 group and 103 procedures (53 patients) in the ESB 4 group: 60.4 and 43.4% had palmar hyperhidrosis, 8.8 and 5.7% had isolated axillary, and 30.8 and 50.9% had combined manifestations, respectively. Follow-up was 22.1 months (obtained from 79.1% of patients) for the ETS 2-4 group and 7.5 months for the ESB 4 group (obtained from 88.7%). RESULTS: The success rate was similar for both groups: 87.9 and 64.5% had completely dry limbs, 9.9 and 35.5% ( p < 0.0002) were nearly dry, and 2.1 and 0% remained wet. (ETS 2-4 vs ESB 4). Although the armpits remained slightly humid in more patients in the ESB 4 group, 100% stated full satisfaction. Complications did not differ significantly. However, compensatory sweating (55.6 vs 8.5%, p = 0.0002) and gustatory sweating (33.3 vs 2.1%, p = 0.0019) were markedly reduced (ETS 2-4 vs ESB 4). Quality of life was assessed by a hyperhidrosis index, which significantly improved in most patients. CONCLUSIONS: ETS 2-4 and ESB 4 have similar success rates in the treatment of upper limb hyperhidrosis. The major side effects of compensatory and gustatory sweating were effectively reduced by the limited method of clipping T4, and patients' satisfaction and improvement in quality of life were remarkable.

Adult↗