Migration of the femoral component and clinical outcomes after total knee replacement: a narrative review.

Loosening is considered as a main cause of implant failure in total knee replacement (TKR). Among the predictive signs of loosening, migration is the most investigated quantitative parameter. Several studies focused on the migration of the tibial component in TKR, while no reviews have been focused on the migration of the femoral component and its influence on patients' clinical outcomes. The aim of this narrative review was (1) to provide information about of the influence of migration in femoral component of TKR prostheses, (2) to assess how migration may affect patient clinical outcomes and (3) to present alternative solution to the standard cobalt-chrome prostheses. A database search was performed on PubMed Central® according to the PRISMA guidelines for studies about Cobalt-Chrome femoral component migration in people that underwent primary TKR published until May 2020. Overall, 18 articles matched the selection criteria and were included in the study. Few studies investigated the femoral component through the migration, and no clear migration causes emerged. The Roentgen Stereophotogrammetric Analysis has been mostly used to assess the migration for prognostic predictions. An annual migration of 0.10 mm seems compatible with good long-term performance and good clinical and functional outcomes. An alternative solution to cobalt-chrome prostheses is represented by femoral component in PEEK material, although no clinical evaluations have been carried out on humans yet. Further studies are needed to investigate the migration of the femoral component in relation to clinical outcomes and material used.

Aggressive treatment for hepatic metastases from breast cancer: results from a single center.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. It has been estimated that approximately 12-20 % of patients will develop liver metastases from breast cancer (BCLM) and that in approximately 5 % of cases the liver is the only metastatic site. Patients with isolated BCLM have the poorest prognosis with a median survival ranging from 19 to 26 months. METHODS: A total of 26 women with isolated BCLM and without any sign of disease progression after a cycle of chemotherapy were retrospectively reviewed. Women were treated with hepatic resection (HR) for unilobar disease or surgical "open" RFA for bilobar disease. Data were collected on either original BC or BCLM and from patients follow-up. RESULTS: Overall survival from BC diagnosis was 47.69 ± 22.25 months (range 33-84, median 45.5 months); it was 52.25 ± 14.57 months (range 33-84, median 48.5 months) for the HR patients and 43.79 ± 27.14 months (range 9-101, median 39 months) for the RFA patients. Overall survival from BCLM treatment was 21.12 ± 12.78 months (range 9-64, median 15.5 months); in detail it was 29.42 ± 14.53 months (range 12-64, median 29.5 months) for the resected patients and 14 ± 4.45 months (range 9-24, median 13.5 months) for patients treated by RFA with a strongly significant survival difference for operated patients (p = 0.001). Overall disease-free survival from BCLM was 15.96 ± 13.16 months (range 3-64, median 12 months), disease-free survival for resected patients was 23.22 ± 16.2 months (range 8-64, median 18.5 months), and for patients treated by RFA was 9.64 ± 4.22 months (range 3-18, median 9 months; Fig. 1). Overall 1, 2, and 5 years (actuarial) survival was respectively 80.7, 57, and 31 %. Given in details for the two groups, they were respectively 100, 66.6 and 34 % (actuarial) for the resected group patients and 64.2, 21.4, and 11.5 % (actuarial) for the RFA patients. Fig. 1 Kaplan-Meier analysis of survival after BC and BCLM treatment. GROUP 1 = resection; GROUP 2 = RFA. Overall survival from breast cancer treatment (months) p = 0.082 ns. Overall survival from BCLM treatment (months) p = 0.001 CONCLUSIONS: Aggressive treatment on isolated BCLM may improve survival for these patients.

A nationwide audit of the use of radiotherapy for rectal cancer in Italy.

BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.

Sporadic, nontrauma-related, desmoid tumor of the pancreas: a rare disease-case report and literature review.

Desmoid tumors (DTs) are neoplasms of fibroblastic origin characterized by lack of a capsule. They are nonmetastatic and locally aggressive. Intraabdominal DTs are often observed in familial adenomatous polyposis and Gardner syndrome or subsequent to localized traumatic injury. Sporadic forms are defined as nontrauma- or nongenetic-related DTs. Isolated, sporadic pancreatic DTs have been considered anecdotal, with only 9 cases described in the literature. We report the case of a 68-year-old man with a case of sporadic cystic DT localized to the pancreatic tail. The tumor was discovered incidentally during computerized tomography performed for an unrelated condition. The patient was asymptomatic; however, biopsy was performed on the clinical suspicion of cystic cancer of the pancreas. Pathology analysis showed fibroblastic proliferation, and the diagnosis of DT was confirmed by immunohistochemical staining for beta-catenin. The patient underwent resection with no further treatment and remain disease-free 60 months after surgery.

Bioartificial liver support. Review and personal experience.

End-stage liver disease is treated successfully by liver transplantation. In spite of the recent advances in transplantation techniques, donor organ shortage remains a serious problem. Conditions such as fulminant hepatic failure are still burdened by a high mortality rate. This has prompted the design of an extracorporeal liver assist device, to "bridge" patients over until they either recover or receive a liver transplant. In these devices, various types of liver cells are inserted and different device designs have been proposed. The paper will review different models of bioartificial liver and will describe ongoing clinical trials. At the end we will report our experimental experience with a newly designed bioartificial liver, evaluating its beneficial effect on acute liver failure.

ALEX (artificial liver for extracorporeal xenoassistance): a new bioreactor containing a porcine autologous biomatrix as hepatocyte support. Preliminary results in an ex vivo experimental model.

Long-term maintenance of viability and expression of differentiated hepatocyte function is crucial for bioartificial liver support. We developed a new bioreactor design (ALEX), associated with a new extracellular autologous hepatocyte biomatrix (Porcine Autologous Biomatrix - PBM) support. To test this new bioreactor, we compared it to a standard BAL (BioArtificial Liver) cartridge in a ex vivo model using human plasma added to bilirubin, ammonium and lidocaine. A pathology study was performed on both bioreactors. The results suggest that ALEX allows a maximal contact between the perfusing plasma and the liver cells and a proper hepatocyte support by a cell-to-matrix attachment. ALEX is a suitable cell support bioreactor, guaranteeing long-term maintenance of the metabolic activity of hepatocytes when compared to a standard BAL cartridge.

Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat.

It has been suggested that administration of a cannabinoid CB(1) (SR141716A ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide) and CB(2) (SR144528 ¿N-[(1S)-endo-1, 3, 3-trimethyl bicyclo ¿2.2.1 heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyr azo le- 3-carboxamide¿) receptor antagonists to mice potentiates inflammatory hyperalgesia by removing an endogenous cannabinoid tone. We examined whether the behavioural response to s.c. formalin injection in rats is similarly enhanced. A total of 30 animals received SR141716A (0.5 or 5 mg/kg) or SR144528 (0.3 or 3 mg/kg) 30 min before 1% formalin. Pain behaviour was quantified using the composite weighted pain score technique (CPS-WST(0,1,2)). An overall CPS-WST(0,1,2) was calculated for each phase and groups were compared (analysis of variance). The results obtained in the control group confirmed the characteristic biphasic behavioural response to formalin injection. None of antagonist groups had a significant increase in overall CPS-WST(0,1,2) compared to the control. Indeed, a significant decrease in CPS-WST(0,1,2) scores for both phases was detected in most of all of the groups, except SR141716A at 5 mg/kg. Levels of endogenous cannabinoids (anandamide, palmitoylethanolamide, 2-arachidonylglycerol) were measured from rats hind-paw skin 1 h after s.c. injection of 0.9% saline (100 microl), 1% (50 microl), 2. 5% (50 microl) and 5% (100 microl) formalin. The concentration of endocannabinoids did not differ between control and formalin-induced inflammation groups. The activity of anandamide amidohydrolase in hind-paw skin also did not change after treatment with formalin. In conclusion, cannabinoid antagonists do not enhance formalin-evoked pain behaviour. These results suggest that, in this model, endogenous cannabinoids do not tonically attenuate inflammatory hyperalgesia.

Liver transplantation. A summary of our surgical practice.

At the turn of the new century, liver transplant procedures can finally be considered an efficient treatment option. Technology has helped transplant intervention become a preferred treatment for patients with progressive and irreversible liver failure. New immuno-suppressive drugs have been introduced which reduce the patient's immunological reaction to the implanted organ, entail minimal side effects and improve practical applications of liver transplantation. As a result of these technological advanced and proper disease management, liver transplant procedures are no longer thought of as an elite therapy, reserved for selected patients with end stage liver disease. In our opinion, it is now a sound and valid surgical option with strictly defined characteristics, indications and well-understood limits. Throughout the past decade, we have studied and applied this type of intervention and have come to terms with its rapid expansion at both the theoretical and practical levels. The most significant obstacle remaining today is the discrepancy between the ever increasing demand and limited supply of organs. The future of liver transplant lies in overcoming this obstacle. Liver transplant practice began at our Institute on 23 November 1990 with the first surgical intervention to replace an organ. In the past 10 years, we have exceeded 200 liver transplant procedures.

Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function.

The amounts, in nine different rat brain regions, of the two endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG), and of the putative AEA precursor N-arachidonoyl-phosphatidylethanolamine (NArPE), were determined by isotope-dilution gas chromatography-mass spectrometry and compared to the number of cannabinoid binding sites in each region. The distribution of NArPE, reported here for the first time, exhibited a good correlation with that of AEA, the former metabolite being 3-13 times more abundant than the endocannabinoid in all regions. The highest amounts of both metabolites (up to 358.5 and 87 pmol/g wet weight tissue, respectively) were found in the brainstem and striatum, and the lowest in the diencephalon, cortex, and cerebellum. These data support the hypothesis that, in the brain, AEA is a metabolic product of NArPE and may reach levels compatible with its proposed neuromodulatory function. The brain distribution of 2-AG, also described in this study for the first time, was found to correlate with that of AEA with levels ranging from 2.0 to 14.0 nmol/g (in the diencephalon and brainstem, respectively). The distribution of the endocannabinoids did not match exactly with that of cannabinoid binding sites, suggesting either that these compounds are not necessarily produced near their molecular targets, or that they play functional roles additional to the activation of cannabinoid receptors. Regional differences in the ligand/receptor ratios may also lead to predict corresponding differences in the efficiency of receptor activation, as shown by previous studies.

Estradiol and testosterone levels in patients undergoing partial hepatectomy. A possible signal for hepatic regeneration?

In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection.

The effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro.

We have previously shown that changes in estrogen-hepatocyte interaction occur during liver regeneration. Following 70% hepatectomy, estrogen levels in the blood were elevated, the number of estrogen receptors in the liver was increased and there was an active translocation of estrogen receptors from the cytosol to the nucleus. The injection of tamoxifen, an estrogen antagonist, inhibits hepatocyte proliferation following partial hepatectomy. The administration of 1 microgram tamoxifen per gm body weight at zero time or 6 hr after the operation resulted in a significant inhibition both of DNA synthesis and of the number of cells in mitosis. Injections of tamoxifen 12 hr or later after the operation had no effect. Concomitant injections of equimolar amounts of estrogen abolished the inhibition by tamoxifen. The effects of estrogen and tamoxifen were also tested on hepatocytes in primary culture. Estrogens in the presence of 5% normal rat serum stimulated hepatocyte DNA synthesis as determined by [3H]thymidine incorporation and the labeling index, whereas epidermal growth factor-induced DNA synthesis in the absence of normal rat serum was strongly inhibited. Tamoxifen, in contrast, inhibited DNA synthesis of hepatocytes in the presence of 5% normal rat serum and reversed the stimulatory effect of estrogen in the same system. Attempts to elucidate the mechanism of tamoxifen inhibition in vitro indicated that one effect of tamoxifen is to prevent the amiloride-sensitive Na+ influx necessary to initiate hepatocyte proliferation.

Orthotopic liver transplantation for fulminant and subacute hepatic failure.

The fulminant hepatic failure (FHF) is a condition characterized by massive hepatocyte necrosis and one that is associated with severe liver and/or other organ-systems insufficiency leading to death in up to 85 per cent of the cases with medical treatment only. Although various expedients have been tried in order to save these patients, the necrosis is usually so massive that it is beyond regeneration. At present, the only hope lies with orthotopic liver transplantation (OLTx), which has become progressively more successful during the last few years. Various considerations pertaining to OLTx are discussed, as well as our series of 40 patients who were transplanted for FHF, with a survival of 57 per cent.

[Changes of plasmatic amino acids in various cases of acute hepatic necrosis and insufficiency in man]. / Variazioni degli aminoacidi plasmatici in alcuni casi di necrosi ed insufficienza epatica acuta nell'uomo.

Changes in total and individual plasma amino acid were examined in subjects with necrosis of the liver and acute insufficiency. Quantitative variations in single amino acids and their percentages were noted in all cases. The extent of such change and the number of amino acids involved were roughly proportional to the degree of insufficiency. A continuous and persistent increase in total blood amino acids can be regarded as a poor prognostic sign, especially if accompanied by a sharp fall in necrosis enzymes. Such an increase, in fact, was only observed in extremely serious cases.