[Show abstract][Hide abstract] ABSTRACT: The components of the kinin system, including kinongens, kininogenases, and B(2) and B(1) receptors, are expressed and activated during inflammation. Here, we investigated the expression of the kinin B(2) receptor messenger RNA, kininogen and kallikrein immunoreactivity, and the ability of kinins to contract control and inflamed gallbladders in vitro.
Human gallbladders, obtained from patients undergoing cholecystectomy either for acute cholecystitis secondary to gallstone disease or during elective gastro-entero-pancreatic surgery (controls), were processed for reverse-transcription polymerase chain reaction analysis, kallikrein and kininogen immunohistochemistry, binding studies, and in vitro contractility studies.
Tissue expression of B(2) receptor messenger RNA and specific binding of [(3)H]-bradykinin increased significantly in acute cholecystitis compared to controls. Kallikrein immunoreactivity was detected in the epithelium and infiltrating leukocytes, whereas kininogen immunoreactivity in the lumen of blood vessels and interstitial space. Bradykinin contracted isolated strips of control and acute cholecystitis gallbladders. In acute cholecystitis tissue, efficacy of bradykinin was higher than that of control gallbladders and similar to that of cholecystokinin. The contraction induced by bradykinin was significantly attenuated by B(2) receptor antagonism but not by cyclooxygenase inhibition and B(1), muscarinic, or tachykinin receptor antagonism.
All the components of the kinin system are expressed in the human gallbladder. Bradykinin is a powerful spasmogen via B(2) receptor activation in the normal and, especially, in the inflamed human gallbladder.
[Show abstract][Hide abstract] ABSTRACT: Malignant lymphoma involving the rectum either as a localized process or as a manifestation of disseminated disease is rare. Several treatments have been proposed and reported, including surgical resection alone or associated with adjuvant chemoradiation, chemotherapy alone, and radiotherapy alone.
A case of bowel obstruction caused by a primary rectal MALT lymphoma is reported. Following emergency loop sigmoid colostomy the patient was started on multiple specific cycles of chemotherapy according to the MACOP-B protocol.
At the end of chemotherapy a remarkable reduction in the size of the tumor was noted. Subsequently the patient underwent an ultralow anterior resection followed by a straight coloanal anastomosis. At 36 months of follow-up the patient is alive with no tumor recurrence.
The present report describes the unique case of a patient with primary obstructing rectal lymphoma treated with neoadjuvant chemotherapy and sphincter-saving curative surgery.
[Show abstract][Hide abstract] ABSTRACT: In view of the very good results obtained by lymphatic mapping and sentinel node biopsy in the staging of patients with melanoma or breast cancer, we investigated the feasibility of intraoperative regional lymphatic mapping in patients with primary colorectal carcinoma. The aim of this study was to determine whether lymphatic mapping and sentinel node assessment can identify aberrant drainage patterns or make for better staging of the neoplasm in those cases with no or only minimal lymphatic neoplastic involvement. Sixteen consecutive patients with primary colorectal cancer (stage T2-T3) but without macroscopic involvement of the lymphatic system underwent intraoperative lymphatic mapping by injecting 1-1.5 ml of isosulfan blue dye. The identified and resected sentinel nodes were examined using conventional haematoxylin-eosin staining and cytokeratin immunohistochemistry. Sentinel node identification was successful in 15 out of 16 cases (93.8%). In 11 cases (73.3%) sentinel node status correctly predicted the final staging. The false-negative rate was 26.7%. Immunohistochemical analysis revealed the presence of micrometastasis in one case (6.7%), which was consequently upstaged. In cases of colorectal cancer lymphatic mapping is an easy, perfectly feasible technique. However, in our experience, it would not appear to significantly improve the accuracy of the histopathological staging of colorectal carcinoma.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study is to analyse the own data and try to discuss if laparoscopic appendectomy offers any advantages in treating young women suffering from pain in right lower abfdominal quadrant.
The study was conducted on 148 patients admitted from October 1993 to December 1998 with diagnosis of of pain in right iliac fossa and operated on with a laparoscopic (LA group: 75 cases) or open approach (OA group: 73 cases). Patients were prospectively randomized on the surgical approach adopted, following a randomized list.
The operative time in LA group was significantly (p < 0.001) longer (87.2 minutes) than for OA group (65.2 minutes). In 2 patients (2.7%) the operation had to be converted. Diagnosis had remained unknown in 16 patients (21.9%) of OA group, in spite of only one case (1.4%) with laparoscopic technique. We didn't observed intraoperative complications. Pain in the first and second postoperative days, evaluated on the use of pain medication, was significantly less in patients in group LA (p < 0.01). There were no deaths. Postoperative complications occurred in 4 patients (5.5%) of group LA, and in 8 patients (10.9%) of group OA. Hospital stay was significantly shorter for those having laparoscopic appendectomy (p < 0.001).
The main advantages of laparoscopic appendectomy consist more in diagnostic accuracy, than in less postoperative pain, less hospital stay and less postoperative complications.
Laparoscopic appendectomy is a safe and accurate approach.
Annali italiani di chirurgia 01/2002; 73(1):59-63. · 0.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this paper is to state the role of radio-guided surgery (RGS) in case of recurrent secondary hyperparathyroidism.
Two cases of recurrent secondary hyperparathyroidism were treated using RGS. After a preoperative assessment, which included ultrasonography (US), MRI and (99m)Tc-radiolabelled sestamibi scan, a radio-guided neck re-exploration was planned. On the day of surgery the patients underwent a radionuclide injection. After 90 min, surgery began.
Dissection was guided by placing the probe in the wound to localize any increased concentration of radioactivity. In the first case the probe identified the gland located deeply in the right tracheo-esophageal groove; in the other case the probe detected a site of increased uptake in the upper mediastinum. Both lesions were dissected and excised; a frozen section confirmed they were parathyroid glands with diffuse hyperplasia. The operative time was less than 60 min in both cases. The patients were discharged on the first postoperative day. A decrease in serum calcium and PTH was observed subsequently. A minimum follow-up of 6 months did not show any recurrence.
RGS can help in detecting the parathyroid tissue in selected cases of renal hyperparathyroidism and makes operation much easier and more predictable.
[Show abstract][Hide abstract] ABSTRACT: We have investigated the ability of protease-activated receptor-1 (PAR-1), PAR-2, PAR-3 and PAR-4 agonists to induce contractile responses in isolated guinea-pig gallbladder. Thrombin, trypsin, mouse PAR-1 activating (SFLLRN-NH2) peptide, and mouse PAR-2 activating (SLIGRL-NH2) and human PAR-2 activating (SLIGKV-NH2) peptides produced a concentration-dependent contractile response.
Mouse PAR-4 activating (GYPGKF-NH2) peptide, the mouse PAR-1 reverse (NRLLFS-NH2) peptide, the mouse PAR-2 reverse (LRGILS-NH2) and human PAR-2 reverse (VKGILS-NH2) peptides caused negligible contractile responses at the highest concentrations tested.
An additive effect was observed following the contractile response induced by either trypsin or thrombin, with the addition of a different PAR agonist (SFLLRN-NH2 and SLIGRL-NH2, respectively). Desensitization to PAR-2 activating peptide attenuated the response to trypsin but failed to attenuate the response to PAR-1 agonists, and conversely desensitization to PAR-1 attenuated the response to thrombin but failed to alter contractile responses to PAR-2 agonists.
The contractile responses produced by thrombin, trypsin, SFLLRN-NH2 and SLIGRL-NH2 were markedly reduced in the presence of the cyclo-oxygenase inhibitor, indomethacin, whilst the small contractile response produced by NRLLFS-NH2 and LRGILS-NH2 were insensitive to indomethacin.
The contractile responses to thrombin, trypsin, SFLLRN-NH2 and SLIGRL-NH2 were unaffected by the presence of: the non-selective muscarinic antagonist, atropine; the nitric oxide synthase inhibitor, L-NAME; the sodium channel blocker, tetrodotoxin; the combination of selective tachykinin NK1 and NK2 receptor antagonists, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2] octane chloride (SR140333) and (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl)-butyl] benzamide (SR48968), respectively.
The results indicate that PAR-1 and PAR-2 activation causes contractile responses in the guinea-pig gallbladder, an effect that is mediated principally by prostanoid release, and is independent of neural mechanisms.
British Journal of Pharmacology (2000) 131, 689–694; doi:10.1038/sj.bjp.0703618
British Journal of Pharmacology 11/2000; 131(4). DOI:10.1038/sj.bjp.0703618 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have characterized the action of the tachykinin NK(2) receptor antagonist nepadutant (c¿[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2 beta-5 beta)¿) in the human isolated ileum, colon and urinary bladder. Nepadutant (30-1000 nM) competitively antagonized neurokinin A- or [beta Ala(8)]neurokinin A-(4-10)-induced contractions in all tissues, with pK(B)=8.3 (ileum and colon) and pK(B)=8.5 (bladder). In contrast, the nonpeptide tachykinin NK(2) receptor antagonist SR 48968 (or (S)-N-methyl-N [4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl) butyl] benzamide) (30-1000 nM) produced insurmountable antagonism in all preparations. The tachykinin NK(2) receptor blockade produced by nepadutant in the colon was fully reversed by washout, whereas that produced by SR 48968 was not. Nepadutant (1 microM) greatly reduced (by 70-80%) the nonadrenergic noncholinergic (NANC) contractile off-response evoked by electrical field stimulation in the human ileum, and almost abolished it in the presence of the tachykinin NK(1) receptor antagonist GR 82334 (or: [[(S,S) Pro-Leu (spiro-gamma-lactam)](9,10),Trp(11)]Physalaemin (1-11)) (1 microM). The present results show that nepadutant is a potent, competitive and reversible antagonist at human tachykinin NK(2) receptors and provide further evidence that tachykinins act as excitatory NANC neurotransmitters in the human small intestine.
European Journal of Pharmacology 07/2000; 398(3):389-97. DOI:10.1016/S0014-2999(00)00346-0 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adenocarcinoma in association with chronic anal fistula is a rare disease which gives rise to difficult problems of diagnosis and treatment. A case of mucinous adenocarcinoma arising on a long standing fistula in ano is described. A patient with a long history of mucinous discharge, pain and perianal induration underwent a biopsy of the external opening of the fistula that showed mucinous infiltrating adenocarcinoma. After a colonoscopy and a preoperative abdominal CT scan, she underwent a successful abdominoperineal resection with adjuvant chemoradiation therapy. Diagnosis of this condition is often difficult; deep and multiple biopsies of the fistulous tracks or perianal mass are necessary to establish the diagnosis. An accurate staging of the neoplasm, using endorectal ultrasound, NMR or CT scans is needed to plan the appropriate treatment. Recent studies have shown that locally advanced anal adenocarcinomas could benefit from pre or postoperative chemoradiation therapy. However, an accurate and complete removal of the tumor, which usually entails abdominoperineal resection, is often necessary to achieve radicality. Despite new therapy protocols, the prognosis of mucinous adenocarcinoma is still poor, mostly due to its advanced nature at the time of diagnosis. This reinforces the importance of biopsy of all perianal abscesses and fistulas for early detection and treatment.
[Show abstract][Hide abstract] ABSTRACT: The affinities of the monocyclic pseudopeptides MEN10,508, MEN10,573, MEN10,581, MEN10,612, MEN10,619 and MEN10,677, and the bicyclic peptides MEN10,627, MEN10,692, MEN10,771, MEN10,882 and MEN10,993 were evaluated at the tachykinin NK2 receptors of the human isolated ileum and colon circular muscle preparations, by using [betaAla8]neurokinin A(4-10) as an agonist. All of the antagonists tested produced a concentration-dependent and competitive antagonism of [betaAla8]neurokinin A(4-10)-mediated contractions in both preparations. MEN10,612 (pKB = 8.1) and MEN10,627 (pKB = 8.4-8.8) were among the most potent analogs within their chemical classes. In general, the bicyclic peptide antagonists were more potent than the monocyclic peptide compounds, showing a nanomolar affinity for the human NK2 receptor. By comparing the affinities shown by the antagonists under study at NK2 receptors of the human gut with the affinities measured at NK2 receptors of the rabbit isolated pulmonary artery and hamster isolated trachea, a high degree of pharmacological homology was found between human and rabbit NK2 receptors. The present results point out the class of NK2 receptor antagonists bearing a bicyclic peptide structure, like MEN10,627, as candidates for testing in pathological conditions characterized by exaggerated gut motility, in which tachykinins might play a role as non-cholinergic excitatory neurotransmitters.
[Show abstract][Hide abstract] ABSTRACT: Good results in terms of control of the disease and 5 years survival have encouraged the use of the sphincter-saving technique for the treatment of cancers of the lower rectum. However, after this operation a percentage of patients complains of functional abnormalities such as increased bowel frequency and modification of continence especially within 12-18 months after surgery. This review analyzes the results of coloanal anastomosis following rectal excision trying to evaluate if the construction of a colonic pouch allows to limit or to prevent the functional anorectal abnormalities that usually follow a straight colo-anal anastomosis.