Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.

[Cytoreductive surgery and intraperitoneal hyperthermic-antiblastic therapy (HAPP) in peritoneal carcinomatosis]. / Chirurgia citoriduttiva e chemioipertermia intraperitoneale (CIIP) nel trattamento delle carcinosi peritoneali.

Peritoneal carcinosis often occurs during the evolution of many neoplasias either abdominal or extra-abdominal. The free time survival of the patients affected by carcinosis is poor (about 6 months) as regards gastric and colorectal cancer. In the last ten-year period a combined surgical technique aiming at the total removal of parietal and visceral peritoneal lesions (peritonectomy) and at the perfusion of peritoneal cavity with chemo-drugs in hyper-thermia had developed. This method is based on the presence of the peritoneal-plasmatic barrier that holds back high molecular weight drugs, keeping from passing at the systemic circulation; in this way it is possible to use higher and more concentrate chemo-drug doses in a very limited area than in the systemic chemotherapy. The association between chemotherapy and hyperthermia produces a synergic effect: hyperthermia, infarct, makes chemo-drugs more effective and selective, improving their capability of penetration in tumoral masses; heat has furthermore an intrinsic anti-neoplastic action, being altered the reparation mechanisms of the tumoral cells. A WEB research on Medline site has been conducted choosing especially those articles referable at the 1999-2000 period. The selected articles have been briefly analysed in the "Clinical experience" section. Authors' experiences have been divided, as far as possible, on the basis of the tumors treatable with cytoreduction and HAPP: 1) Colon-rectal Cancer; 2) Pseudomyxoma peritonei/Appendicular Adenocarcinoma; 3) Gastric Cancer; 4) Ovarian Cancer; 5) Peritoneal Mesothelioma. The determinant variables in the analysis of the results are basically three: 1) Selection of the patients, 2) Characteristics of the surgical operation, 3) Characteristics of the HAPP. Colon-rectal carcinoma: the survival time of the recurrent disease, obtained by some authors like P.H. Sugarbaker, is surely remarkable (50% at 5 years in the patients where a complete cytoreduction was possible to perform), but the result obtained in patients affected by peritoneal carcinosis, subjected to this technique at the first clinical presentation (100% at 5 years) is much more interesting. For this type of neoplasia, it is important to underline that not all the authors report the same results, with a median survival time lower than that of the American author. Pseudomyxoma peritonei: about this rare neoplasia, the "golden standard" treatment consists on cytoreduction of all visceral and peritoneal macroscopical lesions, with a homogeneous distribution of the data obtained by most authors: median survival time included among 70% and 90% at 5 years. Gastric cancer: there is a considerable difference between the data of Japanese authors and others. In the treatment of peritoneal carcinosis the results are, on average, rather poor; better results have been obtained using this technique as an adjuvant presidium for the prevention of the onset of peritoneal carcinosis. Ovarian cancer: the results about the recurrent ovarian cancer are good; in the future, it will be useful to start a phase III study to render effective the use of this technique in the ovarian cancer at the beginning of its clinical story. Peritoneal mesothelioma: till now, a standardized alternative, approaching this neoplasia, does not exist; the results are encouraging, with good median and free time survival.

[Renal protection with amifostine during intraoperative peritoneal chemohyperthermia (IPCH) with cisplatin (CDDP) for peritoneal carcinosis. Phase 1 study]. / Protezione renale con amifostine durante chemioipertermia intraperatoria peritoneale (CIIP) con cisplatino (CDDP) per carcinosi peritoneale. Studio fase I.

BACKGROUND: An innovative approach to peritoneal neoplasm therapy is based on the surgical exeresis of visceral neoplasms, peritonectomy and lastly perfusion of the abdominal cavity with cytostatic drugs in hypothermia (1PCH). Cisplatin (CDDP) is one of the most frequently used drugs for peritoneal perfusion owing to its excellent synergy with hypothermia, reduced ability to penetrate the peritoneal- plasma barrier and its demonstrated efficacy against the majority of neoplasms causing peritoneal carcinosis. A major restriction is that CDDP causes renal toxicity. In order to minimise the risk of renal damage, the authors studied the use of amifostin to protect the renal system. A phase-1 study was performed to find the dose of amifostin that guarantees effective renal protection without causing hypotension. METHODS: A total of 67 cytoreductions were performed at our centre associated with abdominal cavity perfusion using cytostatic compounds in hyperthermia (1PCH) with CDDP for peritoneal carcinosis. Among the first 9 patients undergoing IPCH without nephroprotection, Grade 2 (WHO) renal toxicity was observed in 4 cases (44%) and Grade IV-WHO toxicity in one patient (11%) leading to hemodialysis and death. Arnifastin was then administered to 18 patients. The administration protocol was as follows: cytoreduction, im. administration of amifostin 910 mg/m2 in 15 minutes, execution of IPCH. All patients treated using this dose presented hypotension with systolic arterial pressure <70 mmHg and amifostin administration was consequently suspended. Amifostin was then administered to a further 18 patients divided into groups of three. The dose used for the first triplet was 400 mg/m2; we then increased the dose by 50 mg/m2 in each subsequent triplet. The maximum dose tolerated was 50 mg/m2 less than the initial dose that caused systolic pressure to fall below 70 mmHg. RESULTS: Patients treated with doses = or <500 mg/m2 did not present hypotension and it was therefore possible to administer the entire dose. Patients treated with 600 mg/m2 of amifostin all presented hypotension <70 mg Hg, leading to the suspension of the drug. A new triplet of patients was treated at a dose of 550 mg/m2 and none showed hypotension. Taking 550 mg/m2 as the maximum tolerable dose, a further 22 patients then received amifostin infusion with 550 mg/m2 prior to IPCH. Creatinemia was assayed daily for two weeks and creatinine clearance was measured twice a week to evaluate the efficacy of nephroprotection. None of the patients treated with amifostin during the study died from causes correlated to renal failure: 1 patient died from TEP and 1 from septic shock. No patient treated with a dose of 550 mg/m2 developed arterial hypotension. None of the 18 patients in the dose-finding study presented postoperative creatinemia >1.6 (WHO grade 1 toxicity). In the group of 22 patients treated later, 2 cases (9%) presented creatinemia >1.6 (1.8 and 2.1) for a few days; both had undergone severe debulking and one of the patients subsequently underwent resection and anastomosis of the left renal artery invaded by the neoplasm. CONCLUSIONS: Some patients undergoing cytoreduction+IPCH without the use of amifostin developed severe renal toxicity; acute renal failure occurred in 1 patient requiring hemodialysis and was the main cause of death. None of the 28 patients treated with amifostin 550 mg/m2 developed hypotension or renal insufficiency; only 2 cases showed a slight transient increase in renal function markers. Amifostin appears to be an effective drug for protecting renal emunctory from the toxic effects of CDDP used in cytoreduction+IPCH in patients with peritoneal carcinosis. The dose of 550 mg/m2 used in this study does not cause hypotension and is recommended for this type of clinical use.

New options for aerodigestive tract replacement after extended pharyngolaryngectomy.

OBJECTIVES: Assess the results of a new type of reconstruction of the aerodigestive tract after extended pharyngolaryngectomy. STUDY DESIGN: Follow-up of a total of eight patients who had surgery using ileocolic free graft. METHODS: The surgical technique is described. Five patients underwent pharyngolaryngectomy/cervical esophagectomy, and three patients had total laryngectomy with subtotal pharyngectomy. Patients were monitored to assess complications and recovery of satisfactory swallowing and speech. RESULTS: The technique, thanks to the use of material from the colon, proved to be extremely useful for the reconstruction of the digestive tract. At the same time, ileal anastomosis with the tracheal stump enabled aerodigestive crossing restoration, protected by the ileocecal valve. All patients recovered good swallowing capacity and phoniatric expression, which were obtained by digital occlusion of the tracheostomy, forcing the expiratory air through the ileum and ileocecal valve. Manometric tests also showed that after a while there was a gradual synchronization of swallowing between the transplanted colic segment and the residual esophagus. CONCLUSIONS: The technique described in the present study may be regarded, also in the light of possible further applications, as a new and interesting option for the reconstruction of the aerodigestive tract.

Reconstruction of the pharynx and cervical esophagus using ileocolic free autograft.

BACKGROUND: Advanced stage hypopharyngeal cancer is commonly treated by surgery and radiotherapy. This report presents a technique using ileocolic free autograft as a single-stage procedure for voice and swallowing rehabilitation after pharyngolaryngoesophagectomy. METHODS: Digestive tract restoration is obtained by using the cecum and ascending colon, while the last ileal loop, protected by the ileocecal valve for food and liquid inhalation, is anastomized to the cervical trachea. After abdominal harvesting, the ileocolic complex is transected, transposed, and then revascularized in the cervical field. RESULTS: Six patients underwent this operation successfully with recovery of swallowing function and vocal performance within a short period of time, varying from 18 to 38 days. CONCLUSION: On the basis of achieved results, the ileocolic free autograft can be considered a good option for pharyngoesophageal reconstruction, offering as it does an immediate restoration of swallowing and voice function.

[Ileocolic free autograft in advanced cervical oncology]. / La trasposizione ileo-colica nella patologia oncologica cervicale avanzata.

In head and neck oncology, cancer of the hypopharynx and esophagus still proves difficult to interpret because all treatments give poor results. In order to improve the quality of life for these patients as quickly as possible, one-step reconstructive methods such as the gastric pull-up and free autografts of revascularized intestinal segments are increasingly being used. This work presents a method for a free autograft of the ileocolic segment. After cervical pharyngolaryngoesophagectomy, this method provides a continent aerodigestive carrefour, protected by the ileocolic valve. Three patients successfully underwent this procedure. Deglutition and phonation were recovered quite quickly: between 18 and 38 days. On the basis of the results and after further, more in-depth experience--including adequate follow-up and post-radiotherapy coloesophageal electromanometry to determine the presence and type of motor propulsion exerted by the distal esophagus--the authors conclude that this method is one of the most interesting options available for the surgical reconstruction of pharyngoesophageal circular defects.

[Splenic artery aneurysm. Two successfully operated cases]. / Gli aneurismi dell'arteria splenica. Su due casi operati con successo.

The splenic artery aneurysms usually have an asymptomatic course; their rupture is associated with high mortality. The clinical history and the treatment of two patients with splenic artery aneurysm are reported. Of the two cases, one was asymptomatic, diagnosed with upper abdomen ultrasound, the other one was treated as an emergency because presented with shock. Both patients underwent surgical procedure; ligature of the splenic artery and splenectomy were performed. Early diagnosis is important in these lesions because the progressive enlargement and eventual rupture are the natural history. Ultrasonography (US) and computed tomography (TC) are very helpful as diagnostic tools, however angiography represents the method of choice since it could be the first step of the embolization treatment. If the diameter is more than 2.5 cm surgical treatment must be performed. Ruptures are treated with emergency operations, when possible. In high-risk patients non operative management by selective embolization may be a suitable alternative.

Esophageal dysfunction in scleroderma: relationship with disease subsets.

OBJECTIVE: To investigate the relationship between esophageal function and the extent of disease in a nonselected group of scleroderma patients, and to study gastric and small bowel motility in a group of scleroderma patients with more severe clinical manifestations. METHODS: Esophageal function in 125 scleroderma patients was investigated by radiologic, endoscopic, manometric, and pH-metric techniques. Ten patients also underwent gastrointestinal (GI) manometric recording, both during fasting and after a standard meal. RESULTS: Radiologic abnormalities of the esophagus were found in 55 of 81 patients (68%) and esophagitis in 45 of 125 (36%). No significant relationship was disclosed between GI symptoms, radiologic abnormalities, esophagitis grade, and the various disease subsets. However, the overall incidence of endoscopic esophagitis (irrespective of the degree) was significantly (P < 0.05) correlated with the patient subgroups, with 100% incidence of esophagitis in those having the more severe cutaneous involvement (type III). Manometric abnormalities were documented in 80% of patients, and pathologic reflux in 78%. The severity of esophageal abnormalities on manometry significantly correlated with the severity of the disease, whereas no correlations were found with pH-metric data. Ninety percent of the 10 female patients undergoing antroduodenal manometry displayed abnormal findings; of these, 60% showed neuropathic, and 30% myopathic, patterns. The latter were recorded in patients with a more severe stage of the disease (type III). CONCLUSION: A direct relationship was observed between scleroderma subsets and the severity of esophageal (and, probably, more distal gut) motor involvement. Since no correlation was found between esophageal symptoms and the severity of manometric abnormalities, manometry should be considered the single most important GI test to document the severity of the "esophageal" disease. Gastric and small bowel manometry may also offer evidence of widespread gut involvement, and provide a rationale for a more targeted therapeutic approach.

[Clinical and therapeutic approaches in angina pectoris of esophageal origin]. / Orientamenti clinici e terapeutici nel dolore anginoso di origine esofagea.

The authors, on a basis of experience acquisted since 1984 on two groups of patients, respectively 55 and 174 subjects with angina like chest-pain, individuated in the first group 45%, and 66.1% in the second group, the presence of GER-EMD with the execution of functional stationary manometric and 24 hour pH-metrical exams, without undergoing chemical, pharmacological, mechanical stimulation. They make note that 43 patients out of the second group, underwent, after a certain time, another cardiological study (negative for heart disease when recluted) due to graveness of the symptoms and 33 risulted holders of heart disease, 24 of whom also affected with EMD. The treatment with anti-H2 and procinethycs had succes in 39 patients out of 59, with GER; 10 patients underwent, with success, Nissen-Rossetti funduplication. Medical treatment with sublingual nifedipine was successful in 17 cases out of 56, with EMD; 19 underwent esophageal miotomy surgery commisurated on manometrical dates, with excellent results; 8 patients with hypertension of LES underwent pneumatic dilation with good results; 12 patients live, tolleratig angina like chest-pain. The final considerations are the following: it is not indispensable to look for contemperaly EMD and pain to afferm that pain is of esophageal origin; EMD must be clearly defined; the exclusion primarily of heart pathology must not exclude the possibility of the insorgence of heart desease, in the presence of EMD; the medical therapy, satisfactory in GER, is scarsely efficent in EMD, the decision for surgery must be taken on the gravity of pain associated with an esophageal pathology well defined with numerous diagnostic exams.

[Parapapillary leiomyoma of the second duodenal portion: anatomo-clinical considerations]. / Il leiomioma parapapillare della seconda porzione duodenale: considerazioni anatomo-cliniche.

The authors describe a rare case of leiomyoma situated in the second duodenal portion near the Vater papillary diagnosed for over eight years. The preoperative investigation isn't able to explain certainly the characteristics and the anatomo-topographic relations of the lesion besides the anatomo-pathologic dates have left a border of uncertainty about the benignity of the lesion. These considerations, as agreed with the greater part of authors, show the necessity of early surgical treatment.

[Functional study of intestinal transplants after esophagectomy]. / Studio funzionale dei visceri trasposti dopo esofagectomia.

The Authors contribute their experience covering 228 cases of esophagoplasty after esophagectomy for cancer of the esophagus and of the esophagogastric junction, from 1980 to 1989. Thirty four of these patients (24 EGP, 8 EDP, 2 ECP) underwent accurate functional investigation by X-ray, manometry, pH-metry and scintigraphy. The investigation into esophagogastroplasty in particular revealed that the transposed organ is devoid of motor activity and that emptying is therefore achieved by gravity. It was also shown that the entity of the alkaline, acid and mixed-type reflux is linked to the site of the anastomosis: greater proximity of the anastomosis translates into lower involvement. An investigation into esophagojejunoplasty, instead, highlighted normal motor function: no cases presented reflux of the alkaline type. The two cases of colon plasty investigated presented efficient emptying even though manometry could not detect the presence of motor waves of the propulsive type. The authors conclude that, although the jejunum constitutes the best prosthetic element to transpose from the functional point of view, highly inconsistent and precarious vascularization limits the use of this organ to the higher anastomoses only. Therefore the Authors claim that the stomach, despite its tendency to behave as an inert tube, is still the best choice for transpositions following esophagectomy.

Atypical chest pain: coronary or esophageal disease?

Retrosternal pain can be caused both by cardiac and esophageal disease. This work presents the results of cardiac and esophageal investigations in 55 patients, who had atypical chest pain. Isolated esophageal disease was found in 45% of the subjects while 14.5% had significant coronary arterial disease. Both diseases were found in 10.9% of the patients and neither disease in 29%. We conclude that esophageal disease is very frequent in patients with atypical chest pain but it does not always completely account for the symptoms. Such patients should, in our opinion, be submitted to an electrocardiographic stress test. If the result is positive or non-diagnostic, coronary cineangiography should be performed, irrespective of the results of esophageal investigations. If the electrocardiographic stress test is negative, coronary investigations can be deferred. Esophageal investigations can account for the symptoms in about half of such cases.

[Percutaneous transhepatic treatment of massive intrahepatic calculosis secondary to stenosis of a biliary-digestive anastomosis]. / Trattamento percutaneo transepatico esclusivo di calcolosi intraepatica massiva secondaria a stenosi di anastomosi bilio-digestiva.

The authors describe a successful technique for the percutaneous treatment of intrahepatic gallstones from a stenotic Rouxen-Y hepaticojejunostomy. A bilioplasty of the anastomosis with wash-out of the biliary tract has been achieved through two percutaneous external biliary drainage catheters, one inserted in the right biliary ducts and the other placed in the left biliary ducts by means of an anterior approach.

[Long-term effects of gastric resection on the inferior esophageal sphincter]. / Effetti a distanza della resezione gastrica sullo sfintere esofageo inferiore.

The manometric profile of the oesophagogastric junction has been studied in patients subjected one year earlier to partial gastric resection. A reduction in maximum basal pressure (--49.8%) and length of the lower oesophageal sphincter (--35.45%) were noted. These figures agree with what was observed one month after operation in a previous study. It is concluded that gastric resection lead to a non-transitory reduction in sphincter function.

Tachyphylactic action of high doses of pentagastrin.

The study of the human LES was performed with manometrical methods for atropine action on gastrine tachyphylaxis. Our study points out that there is a complex self regulating neuronal circuit in the LES contraction. We discuss some hypothesis for the LES control. In particular ACh could activate an inhibitory adrenergic muscarinic receptor.