Simultaneous totally robotic rectal resection and partial nephrectomy: case report and review of literature.

INTRODUCTION: The incidence of synchronous RCC and colorectal cancer is heterogeneous ranging from 0.03 to 4.85%. Instead, only one case of huge colon carcinoma and renal angiomyolipoma was reported. The treatment of synchronous kidney and colorectal neoplasm is, preferably, synchronous resection. Currently, laparoscopic approach has shown to be feasible and safe, and it has become the gold standard of synchronous resection due to advantages of minimally invasive surgery. We presented a case synchronous renal neoplasm and colorectal cancer undergone simultaneous totally robotic renal enucleation and rectal resection with primary intracorporeal anastomosis. As our knowledge, this is the first case in literature of simultaneous robotic surgery for renal and colorectal tumor. CASE PRESENTATION: A 53-year-old woman was affected by recto-sigmoid junction cancer and a solid 5 cm left renal mass. We performed a simultaneous robotic low anterior rectal resection and renal enucleation. Total operative time was 260 min with robotic time of 220 min; estimated blood loss was 150 ml; time to flatus was 72 h, and oral diet was administered 4 days after surgery. The patient was discharged on the eighth post-operative day without peri- and post-operative complication. The definitive histological examination showed a neuroendocrine tumor pT2N1 G2, with negative circumferential and distal resection margins. Renal tumor was angiomyolipoma. At 23 months follow-up, the patient is recurrence free. DISCUSSION AND CONCLUSION: As our knowledge, we described the first case in literature of simultaneous robotic anterior rectal resection and partial nephrectomy for treatment of colorectal tumor and renal mass. Robotic rectal resection with intracorporeal anastomosis surgery seems to be feasible and safe even when it is associated with simultaneous partial nephrectomy. Many features of robotic technology could be useful in combined surgery. This strategy is recommended only when patients' medical conditions allow for longer anesthesia exposure. The advantages are to avoid a delay treatment of second tumor, to reduce the time to start the post-operative adjuvant chemotherapy, to avoid a second anesthetic procedure, and to reduce the patient discomfort. However, further studies are needed to evaluate robotic approach as standard surgical strategy for simultaneous treatment of colorectal and renal neoplasm.

Survey of verotoxin-producing Escherichia coli and faecal coliforms in beef carcasses destined for export at slaughterhouses in Brazil

Abstract This study investigated the presence of generic and verotoxin-producing E. coli as well as enumerated faecal coliforms in 30 beef carcasses in different parts of the slaughter process (after skinning, washing and cooling) at each of three slaughterhouses of the state of Mato Grosso do Sul, Brazil. Among the total number of carcasses examined (n = 90), 39 (43.3%) had generic E. coli. Among the 270 samples analysed, 25 (9.3%) were positive after skinning, 14 (5.2%) were positive after washing and nine (3.3%) were positive after cooling. The majority of isolates of E. coli was collected from samples after skinning, which is considered a critical point of the microbial contamination of carcasses. However, the highest concentration of faecal coliforms was found after the washing step. The cooling step proved to be important to reducing the amount of hygiene-indicator microorganisms. The E. coli isolates had no stx1 or stx2 genes associated with virulence.

Involvement of the histaminergic system in the resuscitating effect of centrally acting leptin in haemorrhagic shock in rats.

Leptin, acting centrally as a neuromodulator, induces the activation of the sympathetic nervous system, which may lead to a pressor action in normotensive animals. In haemorrhagic shock, leptin administered intracerebroventricularly (icv.) evokes the resuscitating effect, with long-lasting rises in mean arterial pressure (MAP) and heart rate (HR), subsequent increase in peripheral blood flows, and a 100% survival at 2 h. Since leptin is able to activate histaminergic neurons, and centrally acting histamine also induces the resuscitating effect with the activation of the sympathetic nervous system, in the present study, we investigated an involvement of the histaminergic system in leptin-evoked cardiovascular effects in haemorrhagic shock. The model of irreversible haemorrhagic shock, with MAP decreased to and stabilised at 20 - 25 mmHg, has been used. Leptin (20 µg) given icv. at 5 min of critical hypotension evoked 181.5% increase in extracellular hypothalamic histamine concentration during the first 10 min after injection. Rises in MAP, HR and renal, mesenteric and hindquarters blood flows induced by leptin were inhibited by icv. pre-treatment with histamine H1 receptor antagonist chlorpheniramine (50 nmol). In contrast, there was no effect of H2, H3 and H4 receptor antagonists ranitidine (25 nmol), VUF 5681 (25 nmol) and JNJ 10191584 (25 nmol), respectively. In conclusion, the histaminergic system is involved in centrally-acting leptin-induced resuscitating effect in haemorrhagic shock in rats.

DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian cancer.

Epithelial ovarian cancer has a poor prognosis owing to late diagnosis and frequent relapse after first-line therapy. Analysis of individual genetic variability could aid in the identification of markers, which could help in stratifying patients with the aim of optimizing individual therapy. In this study we assessed polymorphisms in three genes important in drugs' response in 97 early and 235 late-stage ovarian cancer patients. The Asp1104His polymorphism in xpg, a gene important for removal of platinum adducts, was associated with progression-free survival in early- and late-stage ovarian cancer. Our data indicate that a simple diagnostic analysis such as xpg genotyping can help in predicting response, and extension to other possibly relevant genotypes could be useful in selecting patients with epithelial ovarian cancer for optimal therapy and hence increase the chance of response.

Protein kinase C modulates NMDA receptors in the myenteric plexus of the guinea pig ileum during in vitro ischemia and reperfusion.

BACKGROUND: Ischemic episodes lead to profound functional and structural alterations of the gastrointestinal tract which may contribute to disorders of intestinal motility. Enhancement of glutamate overflow and the consequent activation of NMDA (N-methyl-D-aspartate) receptors may participate to such changes by modulating different enteric neurotransmitter systems, including cholinergic motor pathways. METHODS: The molecular mechanism/s underlying activation of NMDA receptors in the guinea pig ileum were investigated after glucose/oxygen deprivation (in vitro ischemia) and during reperfusion. KEY RESULTS: The number of ileal myenteric neurons positive for NR1, the functional subunit of NMDA receptors, and its mRNA levels were unchanged after in vitro ischemia/reperfusion. In these conditions, the protein levels of NR1, and of its phosphorylated form by protein kinase C (PKC), significantly increased in myenteric neurons, whereas, the levels of NR1 phosphorylated by protein kinase A (PKA) did not change, with respect to control values. Spontaneous glutamate overflow increased during in vitro ischemia/reperfusion. In these conditions, the NMDA receptor antagonists, D(-)-2-amino-5-phosphonopentanoic acid [(D)-AP5] (10 µmol L(-1)) and 5,7-dichlorokynurenic acid (5,7-diClKyn acid) (10 µmol L(-1)) and the PKC antagonist, chelerythrine (1 µmol L(-1)), but not the PKA antagonist, H-89 (1 µmol L(-1)), were able to significantly depress the increased glutamate efflux. CONCLUSIONS & INFERENCES: The present data suggest that in the guinea pig ileum during in vitro ischemia/reperfusion, NR1 protein levels increase. Such event may rely upon posttranscriptional events involving NR1 phosphorylation by PKC. Increased NR1 levels may, at least in part, explain the ability of NMDA receptors to modulate a positive feedback on ischemia/reperfusion-induced glutamate overflow.

Involvement of Ca2+-dependent PKCs in the adaptive changes of mu-opioid pathways to sympathetic denervation in the guinea pig colon.

In the guinea pig colon, chronic sympathetic denervation entails supersensitivity to inhibitory mu-opioid agents modulating cholinergic neurons. The mechanism underlying such adaptive change has not yet been unravelled, although protein kinase C (PKC) may be involved. A previous study indirectly demonstrated that activation of mu-opioid receptors on myenteric neurons facilitates PKC activity. Such coupling may counteract the inhibitory action of mu-opioid agents on acetylcholine overflow, since PKC, per se, increases this parameter. After chronic sympathetic denervation such restraint abates, representing a possible mechanism for development of supersensitivity to mu-opioid agents. In the present study, this hypothesis was further investigated. After chronic sympathetic denervation, Ca(2+)-dependent PKC activity was reduced in colonic myenteric plexus synaptosomes. The mu-opioid agent, DAMGO, increased Ca(2+)-dependent PKC activity in synaptosomes obtained from normal, but not from denervated animals. In myenteric synaptosomes obtained from this experimental group, protein levels of Ca(2+)-dependent PKC isoforms betaI, betaII and gamma decreased, whereas alpha levels increased. In whole-mount preparations, the four Ca(2+)-dependent PKC isoforms co-localized with mu-opioid receptors on subpopulations of colonic myenteric neurons. The percentage of neurons staining for PKCbetaII, as well as the number of mu-opioid receptor-positive neurons staining for PKCbetaII, decreased in denervated preparations. The same parameters related to PKCalpha, betaI or gamma remained unchanged. Overall, the present data strengthen the concept that mu-opioid receptors located on myenteric neurons are coupled to Ca(2+)-dependent PKCs. After chronic sympathetic denervation, a reduced efficiency of this coupling may predominantly involve PKCbetaII, although also PKCbetaI and gamma, but not PKCalpha, may be implicated.

[Laparoscopic appendectomy]. / L'appendicectomia laparoscopica.

Most laparoscopic procedures are performed on an elective basis. However, as general surgeons have gained more experience with laparoscopy, they are employing this procedure also for the evaluation and treatment of acute abdominal conditions such acute appendicitis, acute cholecystitis, perforated gastroduodenal ulcer and abdominal trauma, acute pancreatitis and intestinal obstruction. Although its advantages are still under debate, the laparoscopic approach has already been adopted by many centers in the emergency setting.

Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage.

BACKGROUND AND PURPOSE: In circulatory shock, melanocortins have life-saving effects likely to be mediated by MC4 receptors. To gain direct insight into the role of melanocortin MC4 receptors in haemorrhagic shock, we investigated the effects of two novel selective MC4 receptor agonists. EXPERIMENTAL APPROACH: Severe haemorrhagic shock was produced in rats under general anaesthesia. Rats were then treated with either the non-selective agonist [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP--MSH) or with the selective MC4 agonists RO27-3225 and PG-931. Cardiovascular and respiratory functions were continuously monitored for 2 h; survival rate was recorded up to 24 h. Free radicals in blood were measured using electron spin resonance spectrometry; tissue damage was evaluated histologically 25 min or 24 h after treatment. KEY RESULTS: All shocked rats treated with saline died within 30-35 min. Treatment with NDP--MSH, RO27-3225 and PG-931 produced a dose-dependent (13-108 nmol kg-1 i.v.) restoration of cardiovascular and respiratory functions, and improved survival. The three melanocortin agonists also markedly reduced circulating free radicals relative to saline-treated shocked rats. All these effects were prevented by i.p. pretreatment with the selective MC4 receptor antagonist HS024. Moreover, treatment with RO27-3225 prevented morphological and immunocytochemical changes in heart, lung, liver, and kidney, at both early (25 min) and late (24 h) intervals. CONCLUSIONS AND IMPLICATIONS: Stimulation of MC4 receptors reversed haemorrhagic shock, reduced multiple organ damage and improved survival. Our findings suggest that selective MC4 receptor agonists could have a protective role against multiple organ failure following circulatory shock.

Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons.

We have studied the mechanisms underlying nonpathological age-related neuronal cell death. Fifty per cent of neurons in the rat enteric nervous system are lost between 12 and 18 months of age in ad libitum (AL) fed rats. Caloric restriction (CR) protects almost entirely against this neuron loss. Using the ROS-sensitive dyes, dihydrorhodamine (DHR) and 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (HPF) in vitro, we show that the onset of cell death is linked with elevated intraneuronal levels of reactive oxygen species (ROS). Treatment with the neurotrophic factors NT3 and GDNF enhances neuronal antioxidant defence in CR rats at 12-15 months and 24 months but not in adult or aged AL-fed animals. To examine the link between elevated ROS and neuronal cell death, we assessed apoptotic cell death following in vitro treatment with the redox-cycling drug, menadione. Menadione fails to increase apoptosis in 6-month neurons. However, in 12-15mAL fed rats, when age-related cell death begins, menadione induces a 7- to 15-fold increase in the proportion of apoptotic neurons. CR protects age-matched neurons against ROS-induced apoptosis. Treatment with neurotrophic factors, in particular GDNF, rescues neurons from menadione-induced cell death, but only in 12-15mCR animals. We hypothesize that CR enhances antioxidant defence through neurotrophic factor signalling, thereby reducing age-related increases in neuronal ROS levels and in ROS-induced cell death.

Frozen section in thyroid surgery.

OBJECTIVE: We studied the use of frozen section in the detection of malignancy in thyroid surgery in a large teaching hospital. MATERIALS AND METHODS: We reviewed all case notes of patients operated on for thyroid disease between January 1st 1997 and December 31st 2004. We identified 420 operations in 408 patients. Data were available for 417 operations. RESULTS: In patients with a solitary thyroid nodule, a frozen section is sometimes performed. Frozen section was done in 128 of 417 operations. The specificity for malignancy was 98.16%. The positive predictive value was 81.81% and the negative predictive value 93.85%. However the sensitivity was 56.25%. Frozen section is a time-consuming investigation. With follicular lesions it is very difficult to distinguish between benign disease and malignancy since the diagnosis of malignancy depends on capsular and/or blood vessel invasion. Also it costs about 100 Euro (approximately 125 dollars). CONCLUSION: This study confirms that adequate histopathologic diagnosis of thyroid disease is based on extensive subsampling of the specimen which is not possible during a peroperatory frozen section procedure.

A defunctioning stoma in the treatment of lower third rectal carcinoma.

INTRODUCTION: Total mesorectal excision (TME) is the accepted standard for rectal cancer treatment. However, there is an increased risk of symptomatic anastomotic leakage associated with TME as TME potentially endangers the blood supply of the remaining rectum. On top of this, many patients will receive neo-adjuvant radio-chemotherapy. A defunctioning stoma helps in avoiding severe complications of anastomotic failure. MATERIAL AND METHODS: We prospectively collected data of all patients with a rectal carcinoma within reach of the palpating finger, operated on in our department between December 2000 and January 2005. There were 70 patients (42 men and 28 women, median age 70 (range 32-95)). RESULTS: In 40 patients (40/70 = 57%) a sphincter-saving procedure was performed. Eleven patients were diagnosed with anastomotic leakage or failure. Seven patients had neo-adjuvant radio-chemotherapy, 4 had no neo-adjuvant therapy. In 4 patients signs of anastomotic leakage were seen on the barium-enema that is routinely performed before closing the defunctioning stoma. Seven patients (7/40 = 17,5%) had clinical signs of anastomotic leakage. Three of them could be treated conservatively with antibiotics and parenteral nutrition. Two of these patients did not have a defunctioning stoma. Four patients needed re-intervention and were treated in intensive care for several days. Three of these patients did not have a defunctioning stoma. CONCLUSION: Neo-adjuvant radio-chemotherapy and TME resection are two factors in the treatment of rectal cancer that might interfere with anastomotic healing in the case of a sphincter-saving procedure. The construction of a defunctioning stoma helps in limiting the complications of anastomotic leakage or failure.

[Chilaiditi's syndrome: a rare cause of abdominal pain in the differential diagnosis of the abdominal perforation. Case report]. / Sindrome di Chilaiditi: una causa rara di dolore addominale nella diagnosi differenziale della sindrome perforativa addominale. Case report.

A case of a 92-years-old patient with abdominal pain and constipation is presented. He reported a recent traumatic fracture of the upper limb. Traditional diagnostic work-up for patient with abdominal pain was started up. He was submitted to abdominal film that demonstrated air underneath the diaphragm suggestive for perforation. This hallmark is opposed to clinical condition of patient, so differential diagnosis for rare Chilaiditi's syndrome was considered, because this syndrome is frequent in old patient. Diagnostic work-up was completed with upper abdominal CT that excluded intestinal perforation and confirmed the diagnosis of Chilaiditi's syndrome showing hepatodiaphragmatic interposition of the dilated colon. Therefore it was decided in favour of medical therapy. In the our case, in spite of negative clinical examination, the uncertain radiological hallmark obliged us to exclude diagnosis of abdominal perforative syndrome that needs emergency operation. Although the Chilaiditi's syndrome is rare, it must be considerated in differential diagnosis of perforative abdominal syndrome, when there are doubts about the subdiaphragmatic air in abdominal film.

Effects of ketamine anesthesia on central nociceptive processing in the rat: a 2-deoxyglucose study.

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis.

Can interposition of a silicone implant after sapheno-femoral ligation prevent recurrent varicose veins?

OBJECTIVES: To investigate whether a silicone implant at the sapheno-femoral ligation site could prevent recurrent varicosities. MATERIALS AND METHODS: Two non-randomised groups of patients were studied prospectively. In group A 173 patients and 212 limbs had sapheno-femoral ligation, while 172 patients and 210 limbs additionally had a piece (2x3cm) of silicone sheet sutured to the saphenous stump to cover the anterior half of the common femoral vein. The implant was fixed in apposition to the deep vein by carefully closing the cribriform fascia. Colour duplex scanning was performed after 2 and 12 months. RESULTS: In the no implant group neovascularisation was observed in 35 (17%) after 12 months, but only in 13 (6%) limbs treated with a silicone implant (p<0.05). CONCLUSIONS: Interposition of a partition of silicone implant seems to lower the incidence of neovascularisation one year after saphenofemoral ligation. This technique may constitute an efficient method to prevent recurrence at the correctly ligated saphenous stump.

Modulatory activity of sildenafil on copulatory behaviour of both intact and castrated male rats.

The first experiment of the present study investigates the effects induced by sildenafil (1 or 10 mg/kg po) on the copulatory behaviour of intact male rats, categorized, on the basis of seven consecutive mating pretests, as sluggish or normal ejaculators (SE or NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and the ejaculatory mechanisms of copulation, diminishing ejaculation latency in both categories and increasing copulatory efficacy in SE rats; in addition, it reduced the inter-intromission interval in both SE and NE animals and the post-ejaculatory interval only in SE animals. The second experiment, conducted on rats 3 weeks after their castration, shows that sildenafil alone (1 or 10 mg/kg) did not modify copulatory failure. However, 3 months after castration, and 24 h after the last injection of testosterone (25 microg/kg sc) given twice weekly for 4 weeks, sildenafil (1 or 10 mg/kg) ameliorated rat copulatory performance.

Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator male rats: a central dopamine mediated effect?

The present study investigates the effects induced by sildenafil (1 mg/kg, p.o.) and the dopamine agonist, SND 919 (0.1 mg/kg, i.p.) on copulatory behaviour of male rats, categorized, on the basis of seven consecutive mating pre-tests, as sluggish and normal ejaculators (SE and NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and ejaculatory mechanisms of copulation. It appears that, although it induced a facilitatory effect on ejaculation of all rats, similarly to SND 919, the lowering of ejaculatory threshold was achieved by means of a reduction of mount frequency and intromission frequency in SE and NE groups, respectively. Differently from SND 919, sildenafil increased sexual arousal, diminishing post ejaculatory interval in SE animals and inter-intromission interval in both SE and NE rats. As the dopamine antagonist, (-)eticlopride (0.02 mg/kg, s.c.), significantly inhibited sildenafil-induced enhancement of sexual arousal in SE rats, it is suggested that the drug acts both peripherally and centrally.

Influence of sildenafil on central dopamine-mediated behaviour in male rats.

Two experiments were performed to evaluate the effects of sildenafil on spontaneous or dopamine agonist-induced behaviour in male rats. Data obtained in experiment 1 show that oral administration of the drug, at 1 mg/kg, significantly increased the occurrence of penile erections, anogenital self-grooming and homosexual mounting in grouped sexually-experienced, but not inexperienced, animals. In experiment 2, pre-treatment with sildenafil (0.5, 1 or 10 mg/kg) dose-dependently modified several behavioural signs, centrally evoked by the D2/D3 dopamine agonists, 7-OH-DPAT or B-HT 920 (both at 0.1 mg/kg), in experimentally naive male rats. While sildenafil at 1 mg/kg significantly increased the number of penile erection and stretching-yawning episodes induced by 7-OH-DPAT or B-HT 920, at 10 mg/kg it elicited low stereotyped behaviour, antagonizing stretching-yawning and sedation in 7-OH-DPAT treated rats. Discussion centres on the modulatory activity of sildenafil on central dopaminergic pathways and, possibly, on nitric oxide production.

Congenital right-sided diaphragmatic hernia in an elderly patient. A case report.

Congenital diaphragmatic hernia is a rare condition in adulthood. It is even more exceptional when located on the right side. We describe a case of right-sided congenital diaphragmatic hernia in a 74-year old woman. The diagnosis was only made when the patient developed an acute intestinal obstruction after a laparotomy for a gynaecological benign tumour. The treatment of this condition is discussed. In our opinion, in elderly, the advantages of an elective operation in asymptomatic congenital diaphragmatic hernia have to outweigh the risks of the operation. However, if the patient shows symptoms of pulmonary dysfunction or motility disorders of the gut, or even when he has to undergo a laparotomy for a different reason, we advise to repair the hernia in order to prevent complications.

Hu 210: a potent tool for investigations of the cannabinoid system.

The synthetic compound HU 210 displays a multiplicity of biochemical, pharmacological, and behavioral effects, most of which have been demonstrated to be dependent on a selective agonistic activity at CB(1) and CB(2) cannabinoid receptors and to involve the main neurotransmitter systems. Results obtained in various studies suggest a potential clinical application of this highly potent drug (e.g., as antipyretic, antiinflammatory, analgesic, antiemetic, and antipsychotic agent) as well as its usefulness in research aimed to develop a better understanding of the involvement of the endogenous cannabinoid system in a number of physiopathological functions.