Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects.

OBJECTIVE: To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. DESIGN AND SUBJECTS: Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. RESULTS: BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. CONCLUSION: Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

Consequences of frequent nocturnal gastro-oesophageal reflux disease among employed adults: symptom severity, quality of life and work productivity.

BACKGROUND: Effects of frequent nocturnal symptoms of gastro-oesophageal reflux disease (GERD-FNS) on health-related quality of life (HRQOL) and work productivity are not well documented. AIM: To assess symptom severity, production loss, and HRQOL among employed adults with and without GERD-FNS. METHODS: Using several validated outcome measures in a web survey design, GERD was pre-specified as GERD Symptom and Medication Questionnaire score >9, and > or =1 episode of heartburn or acid regurgitation during the preceding week. GERD-FNS patients were those reporting > or =2 symptom-nights during the previous week; their outcomes were compared with those of patients having minimal or no nocturnal symptoms (GERD-NNS) and vs. non-GERD controls. RESULTS: Data were collected from 1002 GERD patients (476 GERD-FNS, 526 GERD-NNS) and 513 controls. Severe symptoms were more common, sleep abnormalities were more frequent (P < 0.0001) and SF-36 scores lower (P < 0.05, all scores) among GERD-FNS patients vs. GERD-NNS patients. GERD-related work loss was greater among those with GERD-FNS vs. GERD-NNS (P < 0.0001). Work loss and functional limitations were more pronounced when comparing GERD-FNS cases vs. non-GERD controls. CONCLUSION: Employed adults with frequent nocturnal GERD report more severe symptoms, and are associated with impaired sleep, HRQOL and work productivity compared with controls and patients with minimal or no nocturnal symptoms.

Photodynamic therapy outcomes in a case of macular choroidal neovascularization secondary to Candida endophthalmitis.

PURPOSE: To evaluate the effects on visual function and choroidal neovascularization (CNV) progression in a case of subretinal CNV due to Candida endophthalmitis treated with a combination of photodynamic therapy (PDT) and drugs. METHODS: A 28-year-old one-eyed woman with CNV in the right eye came to our observation. The CNV developed as a consequence of Candida endophthalmitis. The CNV was treated with six PDT treatments with verteporfin in association with systemic steroid therapy with prednisone (100 mg/day to reduce) and fluconazole (800 mg/day to reduce). Visual acuity (VA) was assessed in pre-PDT conditions and after six PDT treatments (24 months of follow-up). RESULTS: Pre-PDT VA was 20/125; after 24 months of follow-up, six PDT re-treatments, and pharmacologic therapy, VA was stabilized at 20/100. CONCLUSIONS: In our case, associated PDT and drug therapies were safe and useful to maintain VA and to arrest CNV progression in the foveal region after 2 years of follow-up.

Quality of vision: A consensus building initiative for a new ophthalmologic concept.

PURPOSE: Many studies have addressed the quantification of visual acuity, and the conventional method of measuring it has so far demonstrated serious limitations. Vision testing requires new methods that can more precisely express the quality of vision as perceived by the patient. METHODS: This study employed the Delphi method of consensus building. Concepts associated with quality of vision (QoV) were identified by a board of experts and proposed to participating specialists in two subsequent questionnaires. Upon receipt of the completed questionnaires, the replies were classified to determine the building blocks of a consensus. RESULTS: By analyzing the replies to the two questionnaires, the authors determined the key elements of QoV on which a consensus was found among the respondents. CONCLUSIONS: A consensus was reached on the opinion that the quantification of visual acuity by traditional means is inadequate for investigating QoV. Although visual acuity is still a basic element for testing, the experts believe that contrast sensitivity, reading speed, and microperimetry are additional parameters necessary for quantifying QoV. The use of a psychometric questionnaire on visual function could allow a better interpretation of visual impairment.

Reduced glutathione protects against cisplatin-induced neurotoxicity in rats.

Reduced glutathione (GSH) is reported to diminish cisplatin-induced neurotoxicity, and it was for this reason that we studied GSH in an animal model of cisplatin neuropathy. The neuropathy was evaluated by measuring the sensory nerve conduction velocity (SNCV) in young adult Wistar rats. GSH injections (i.v.) were given twice weekly, within five minutes before cisplatin was injected (i.p.). In a first experiment GSH (500 mg/kg) in combination with a low-dose cisplatin treatment (1 mg/kg, 10 weeks) was investigated. Animals treated with cisplatin and placebo developed a neuropathy (SNCV at week 10: age controls, 61.9 m/s; cisplatin alone, 44.2 m/s), whereas rats treated with cisplatin and GSH did not (SNCV, 61.9 m/s). The same dose of GSH was used in combination with a high-dose cisplatin schedule (2 mg/kg, 5 weeks' treatment plus 5 weeks' recovery). Again, GSH protected animals against the development of neuropathy (SNCV at week 10: age controls, 61.9 m/s; cisplatin alone, 50.6 m/s; cisplatin plus GSH, 61.1 m/s). In another experiment four lower doses of GSH (25, 50, 100, and 200 mg/kg) were tested in combination with the low-dose cisplatin protocol (1 mg/kg, 11 weeks). The cisplatin group developed a neuropathy (SNCV at week 11: cisplatin alone, 50.2 m/s; age controls, 60.6 m/s). Only the dose of 200 mg GSH/kg was found to protect against the development of a neuropathy (SNCV, 61.0 m/s). In an antitumor study GSH administered at 300 mg/kg in combination with cisplatin at 1.5 mg/kg did not diminish the curative effect of cisplatin. We conclude that GSH prevents cisplatin-induced neuropathy and that it should be investigated further in the clinic.

Primum Non Nocere: Organ Donation After Electrocution and Transplantation of Electricity-Damaged Livers: Report of 2 Cases.

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts.

Aflibercept in persistent neovascular AMD: comparison of different treatment strategies in switching therapy.

PurposeTo evaluate the effects of aflibercept administered according to a pro re nata (PRN) or Fixed Regimen to patients with neovascular AMD and persistent intraretinal/subretinal fluid (IRF/SRF) despite three consecutive ranibizumab injections.MethodsPatients were switched to aflibercept injection (IVA) administered according to a PRN or to a fixed regimen for 1 year in two different retina centers. At baseline each patient underwent a complete ophthalmologic evaluation, including best-corrected visual acuity assessment (BCVA ETDRS chart), fluorescein, and indocyanine green angiography and OCT.ResultsEach group included 36 eyes. After 1 year the PRN group showed BCVA stabilization (63 vs 60 letters, P=0.33), whereas fixed regimen group showed significant BCVA improvement (68 vs 71, P=0.008). The median central retinal thickness decreased by 94 µm in the PRN (P=0.002) and by 148 µm in the fixed regimen group (P≤0.001). Complete IRF/SRF reabsorption was found in 58% of eyes in the PRN and in 42% of eyes in the fixed regimen group. At 1-year visit, the percentage of eyes with pigment epithelium detachment did not significantly decrease, but a height reduction was recorded in both groups. The median number of IVA was 3.5 in the PRN and 7 in the fixed regimen group.ConclusionThe switch to aflibercept with both treatment strategies enabled improvement in morphological parameters and stabilization of visual acuity. BCVA improvement and reduction in vision loss with reduction in retinal thickness, fluid and PED height was achieved with the fixed regimen in previously treated nAMD after 1 year.

Surgical management of the pancreatic stump following pancreato-duodenectomy.

Pancreato-duodenectomy (PD) is the treatment of choice for periampullary tumors, and currently, indications have been extended to benign disease, including symptomatic chronic pancreatitis, paraduodenal pancreatitis, and benign periampullary tumors that are not amenable to conservative surgery. In spite of a significant decrease in mortality in high volume centers over the last three decades (from>20% in the 1980s to<5% today), morbidity remains high, ranging from 30% to 50%. The most common complications are related to the pancreatic remnant, such as postoperative pancreatic fistula, anastomotic dehiscence, abscess, and hemorrhage, and are among the highest of all surgical complications following intra-abdominal gastro-intestinal anastomoses. Moreover, pancreatico-enteric anastomotic breakdown remains a life-threatening complication. For these reasons, the management of the pancreatic stump following resection is still one of the most hotly debated issues in digestive surgery; more than 80 different methods of pancreatico-enteric reconstructions having been described, and no gold standard has yet been defined. In this review, we analyzed the current trends in the surgical management of the pancreatic remnant after PD.

Transcription of the non-repetitive genome in liver hypertrophy and the homology between nuclear RNA of normal and 12 H-regenerating liver.

The percentage of the non-repetitive genome transcribed and the complexity of nuclear RNA were estimated in normal and 12 h-regenerating rat liver. Nuclear RNA from normal or 12 h-regenerating liver hybridizes with approximately 6.1% of non-repetitive DNA (12.2% of the single-copy genome, assuming assymetric transcription). The estimated complexity of either of these nuclear RNA populations is 7.6 . 10(10) daltons, which is approximately 7 times higher than that calculated for polysomal mRNA. Cross hybridization experiments did not show differences between the nuclear RNA populations of normal and 12 h-regenerating liver. The results indicate that liver hypertropy (without hyperplasia) may be brought about without a large increase in the proportion of the non-repetitive genome transcribed.

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin.

The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.

Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies.

The bioequivalence of two megestrol acetate formulations, 160-mg "tablets" and 160-mg "sachets," was investigated in a single-dose, open-label, balanced-for-sequence cross-over study involving 12 advanced-cancer patients. The observed plasma megestrol-acetate time course obtained with both formulations was consistent with the literature data. The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role. The width of the 90% confidence interval of the area-under-the-curve (AUC) ratio (sachets: tablets) computed according to Schuirmann (0.9-1.4) was mainly due to the presence of a single outlier, showing an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose-response data reported in the literature.

Low-dose glutathione administration in the prevention of cisplatin-induced peripheral neuropathy in rats.

So far various drugs have been used in an attempt to prevent or reduce cisplatin (CDDP)-induced peripheral neuropathy. Of those tried reduced glutathione (GSH) is one of the most promising. Its effectiveness has already been demonstrated by means of morphological methods in CDDP-treated rats in which high doses of GSH (up to 1200 mg/kg) were given. In the current study neurophysiological and morphological methods were used to evaluate the effect of low doses (150-300 mg/kg) of GSH i.p. on the peripheral nervous system of the rat. Four groups of 8 female Wistar rats were treated as follows: (A) CDDP 2 mg/kg i.p. weekly for 9 courses; (B) same as (A) plus GSH 150 mg/kg i.p. weekly; (C) same as (A) plus GSH 300 mg/kg i.p. weekly; (D) same as (A) plus GSH 150 mg/kg i.p. on the day of DDP injection followed by 150 mg/kg/day over the next 2 days. Eleven age-matched untreated rats were used as controls. Sensory conduction velocity was recorded in the tail nerve and morphologic and morphometric examinations were performed on the dorsal root ganglia neurons (L4-L6) in each animal. The results demonstrated that the neurophysiological and pathological changes induced by CDDP administration were less severe in rats co-treated with GSH. No significant differences could be related to the 3 different regimens of GSH co-treatments. This experiment confirms that GSH is able to reduce the neurotoxicity of CDDP and that it is effective even at doses as low as those used in the present study.

Neuroprotectant drugs in cisplatin neurotoxicity.

Cisplatin (CDDP) is one among the most effective and widely used anticancer drugs. Its use is, however, often limited by its peripheral neurotoxicity, which may be severely disabling and sometimes not reversible. To prevent or reduce CDDP peripheral neurotoxicity several "neuroprotective" drugs have been proposed. This goal is of extreme importance in the treatment of cancer patients, especially in view of the better results obtained by anticancer chemotherapy in terms of longer disease-free survival which has made even more crucial than in the past the point of the quality of life of the long-surviving patients. The data of pre-clinical and clinical studies with neuroprotectant agents are often conflicting, in some cases because of inadequate methods of evaluation and/or study design used to examine their effectiveness. The aims of this review will be 1) to discuss and describe the most appropriate methods of evaluation of CDDP and neuro-protectant drugs in experimental in vitro and in vivo pre-clinical studies 2) to evaluate critically the results of the clinical trials reported so far with the combined treatment and 3) to explore the possible future strategies to achieve neuroprotection during high-dose CDDP treatment in humans.

A feasibility study of cisplatin administration with low-volume hydration and glutathione protection in the treatment of ovarian carcinoma.

Glutathione (GSH) is a sulfur-containing nucleophile that protects against cisplatin-induced renal toxicity without reducing the antitumor activity of the cytotoxic agent. To document further the clinical role of GSH in improving the outcome of cisplatin-containing regimens, the feasibility of the GSH/cisplatin combination using a low-volume hydration protocol was evaluated in untreated ovarian cancer patients. Twelve patients at stage III (minimal residual disease) and 23 with localized disease at high risk for recurrence were treated with cisplatin (90 mg/m2, i.v. in 250 ml of normal saline over 30 min) and cyclophosphamide (600 mg/m2 i.v.) every 3 weeks. GSH (5 g in 200 ml of normal saline) was administered by a short-term infusion (15 min) prior to cisplatin. The hydration protocol consisted of 1 liter of fluids without diuretics. The treatment was well tolerated; no nephrotoxic or neurotoxic manifestations were observed. The renal excretion of cisplatin (23%) at 24 hours following infusion was lower than expected using a standard i.v. hydration protocol. No reduction of renal elimination of cisplatin could be detected in subsequent courses, thus suggesting a minimal degree of impairment in renal function. In the series of evaluable patients (11) with stage III disease, 9 had complete pathological response. In the series of patients with no clinically detectable disease initially, all were disease-free at treatment completion. Taken together with previous observations, these results support the view that the use of GSH is a successful approach in the attempt to optimize cisplatin treatment, providing a new modality of drug administration for out-patient treatment.

Weekly cisplatin +/- glutathione in relapsed ovarian carcinoma.

On the basis of experimental data showing the efficacy of glutathione (GSH) as a protective agent on cisplatin-induced neurotoxicity and the clinical evidence of the low incidence of neurotoxicity in high-dose cisplatin + GSH treated patients we evaluated the neuroprotective effect of GSH in a randomized phase II study. Thirty-three patients with relapsed ovarian cancer after a disease-free interval of at least 1 year and a cumulative dose of prior cisplatin ranging 450-650 mg m-2 were randomized to receive cisplatin 50 mg m-2 weekly +/- 2.5 g GSH for 9 consecutive weeks. Clinical and instrumental neurologic and otologic evaluations were made at the baseline and at the end of the study. Overall response rate in 31 evaluable patients was: 9/15 in group A and 12/16 in group B, including 4/15 vs 7/16 complete responses. The administered dose intensity of cisplatin was higher in the GSH treated patients (100% dose intensity was received by 56% vs 27%). A trend in terms of neuroprotection was detected in the GSH treated group, and no major difference was observed in the other toxicities between the two groups. It is concluded that possible benefit can be expected from the concomitant administration of GSH and cisplatin in patients at high risk of developing neurotoxicity, without decreasing the anti-tumor activity.

A preliminary clinical study of cyclophosphamide with reduced glutathione as uroprotector.

Reduced glutathione (GSH) has been reported to be an effective protector against cyclophosphamide-induced urotoxicity in experimental models, providing protection comparable to that of mesna. This paper describes our preliminary results of the clinical use of GSH in combination with cyclophosphamide. GSH was administered i.v. in two divided doses of 2.5 g, 15 min before and 30 min after escalating doses of cyclophosphamide ranging from 1.2 up to 1.6 g/m2 (1-h infusion). GSH was well tolerated and did not produce unexpected toxicity. The lack of bladder damage, including microscopic hematuria, supports the protective role of this thiol compound.

A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity.

AIMS AND BACKGROUND: The clinical use of cisplatin (CDDP), one of the most active agents in advanced ovarian cancer, is limited by nephrotoxicity and cumulative neurotoxicity. In preclinical studies, reduced glutathione (GSH) demonstrated a protective action against CDDP nephrotoxicity. We treated 20 patients with advanced ovarian carcinoma, with polychemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. METHODS: Between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-IV-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cyclophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v. in normal saline 100 ml (in 15 min), before CDDP, every 21-28 days. RESULTS: A pathologic complete response rate (PCR) of 55% (11/20) was observed (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicity was limited, without any case of nephrotoxicity. CONCLUSIONS: On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies.

Potential infectivity of blood from HBsAg asymptomatic carriers due to the presence of HBV-DNA and comparison with other markers of HBV infection.

Serum samples from 356 HBsAg positive asymptomatic carriers, which were titrated by reverse passive hemagglutination, were analysed for the presence of HBV-DNA, HBsAg and IgM anti-HBc. The samples were divided in three classes, according to the titers of HBsAg and IgM anti-HBc and the distribution of HBV-DNA and HBsAg among these classes was studied. In the high titer class of HBsAg, 65% of samples have one or both markers against only 19% in the low titer class. From the total of 356 samples, 121 gave positive results for IgM anti-HBc (33.9%). From these, 38.9% of HBV-DNA and 47.9% of HBeAg were observed, whereas in samples with absence of IgM anti-HBc, 18.3% and 16.6% were respectively found. A higher frequency of agreement between all these markers was found in the class of high titers of HBsAg; however, HBV-DNA was detected in the low titer class of HBsAg and little or no IgM anti-HBc, showing potential blood infectivity even in HBsAg positive borderline samples.

[Phantom rectum after Miles' operation]. / Il retto fantasma dopo intervento di Miles.

The authors observed symptoms relating to the existence of a phantom rectum, a phenomenon about which little is still known, in 233 cases (32.1%) in a series of 724 patients undergoing amputation of the abdomino perineal rectum due to malignant neoplasm. The genesis of this phenomenon is attributed to an abnormal reactivity of the cortical and thalamic projection areas with greater response to stimuli from the stump or aspecific visceral stimuli, or even stimuli from the adjacent cortical regions. The psychodynamic aspects linked to the patient's need to develop a different body awareness should not be underestimated; this has to integrate a new anatomic reality, such as colostomy in the place of the anorectum, entailing the relinquishment of the previous body scheme. Prevention and treatment of phantom rectum, which is painful in 27% of cases, is essential for a correct operating technique, adequate psychotherapeutic support, the patient's active participation in a reeducation programme for colostomy management. It should not be forgotten that painful phantom rectum, especially with late onset, may be diagnostically significant as an indicator of the recurrence of neoplastic pathology, sometimes allowing diagnosis to be anticipated by several months. This underlines the importance of carrying out a careful postoperative clinical, biohumoral and radiological control in these patients, including pelvic CT. In the authors' experience of 233 patients suffering from phantom rectum, it was possible to document the presence of neoplastic recidivation in 30 cases (12.8%) using pelvic CT. In these cases, symptoms appeared after a disease-free interval of 26.3 months (range 3-75 months), whereas the presence of phantom rectum without recidivation is usually described in the first 2 months after surgery.