[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.

[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.

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.

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.

[Surgical treatment of postoperative peptic ulcer]. / Considerazioni sul trattamento chirurgico dell'ulcera peptica post-operatoria

The literature on postoperative peptic ulcer is reviewed and cases observed in the Department of Surgical Anatomy and Operations Course of Turin University in the period 1-I-1968 - 31-III-1975 are presented. 183 operations for primary gastro-duodenal ulcer were carried out. A variety of techniques was employed, including 138 gastric resections using a modified Billroth II technique, with a recurrence of 1.3% encountered only in patients in the specified group. 15 reoperations for postoperative peptic ulcer were performed with the following result: very good in 7 cases, good in 6, and 2 postoperative deaths. The two deaths concerned a simple gastric reconversion and a gastric re-resection with gastro-jejuno-anastomosis. The personal series confirms the statistics presented by numerous foreign workers.