[Prognostic factors in gastric cancer. Our experience and review of the literature]. / Fattori prognostici nel cancro gastrico. Nostra esperienza e revisione della letteratura.

BACKGROUND: This review of the latest literature and retrospective analysis of the authors' series aimed to identify the most relevant prognostic factors for gastric cancer. METHODS: A total of 81 patients were operated in our series from 1980 onwards. Eighteen patients underwent minor surgery and 5 were not treated. All resected patients underwent R2 lymphadenectomy. RESULTS: In the majority of cases the histiotype was found to be adenocarcinoma. Undifferentiated forms were only found in 8 cases. The prognostic factors identified in our series and in the most recent literature were age, lesion sites, histiotype, the number of metastatic lymph nodes and T3. The poor prognosis in younger patients may be explained by late diagnosis and more aggressive tumours. Neoplasms in the upper third of the stomach have a worse prognosis owing to a faster metastasis rate, lymphatic drainage directly into the left para-aortic lymph nodes and lack of serosa in the gastric fundus, meaning that in practice T2 becomes T3. Lymphatic diffusion represents one of the most important factors, in particular the number of lymph nodes affected by the tumour is decisive for prognosis: from the literature, in both T1-T2 and T3-T4, if > or = 5 lymph nodes are positive then survival rates decrease significantly. CONCLUSIONS: From our personal experience, N2 determines the prognosis in both T2 and T3. N2 is important, but survival diminishes in T3, thus demonstrating the importance of serous infiltration. The majority of Western and Japanese authors deem that T3 represents one of the decisive factors.

Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.

The aim of the study was to verify the effects of the administration of an inhibitor of the release of endogenous vasodilators together with a vasoconstrictor agent in patients with hepatorenal syndrome (HRS). This new medical perspective was compared with a traditional medical approach for HRS, such as the infusion of nonpressor doses of dopamine to produce renal vasodilation. Thirteen patients with type 1 HRS were enrolled in the study. Five of them were treated with the oral administration of midodrine and the parenteral administration of octreotide. In addition, the patients received 50 to 100 mL of 20% human albumin solution daily for 20 days. Midodrine and octreotide were dosed to obtain a stable increase of at least 15 mm Hg of mean arterial pressure. Eight patients were treated with the intravenous administration of nonpressor doses of dopamine (2-4 micrograms/kg/min) and the same daily amount of albumin. After 20 days of treatment with midodrine and octreotide, an impressive improvement in renal plasma flow (RPF), glomerular filtration rate, and urinary sodium excretion was observed in patients. This was accompanied by a significant reduction in plasma renin activity, plasma vasopressin, and plasma glucagon. No side effects were observed. Three patients were discharged from the hospital. One of them successfully underwent liver transplantation. One of the two remaining patients is still alive after 472 days with a preserved renal function, and the other died from terminal liver failure after 76 days. One of the two patients who were not discharged from the hospital successfully underwent liver transplantation, and the other died from pneumonia after 29 days. Seven out of eight patients who were treated with dopamine experienced a progressive deterioration in renal function and died during the first 12 days. Only one patient recovered renal function and underwent liver transplantation. In conclusion, the long-term administration of midodrine and octreotide seems to be an effective and safe treatment of type 1 HRS in patients with cirrhosis.

Splenic Doppler impedance indices: influence of different portal hemodynamic conditions.

The spleen plays a pivotal role in the pathogenesis and maintenance of portal hypertension. Few data exist about splenic hemodynamics evaluated by duplex sonography in this condition. Twenty-six normal subjects, 207 patients with portal hypertension of various causes, and in different splenoportal hemodynamic conditions, and 31 patients with liver transplantation were evaluated. In each patient the splenic resistive index (RI = peak systolic--end diastolic velocity/peak systolic velocity) and pulsatility index (PI = peak systolic--end diastolic velocity/mean velocity) were measured. In 17 cirrhotic patients, splenic indices were compared with portal hemodynamics as invasively evaluated by hepatic vein catheterization. In the various groups, RI and PI were respectively: normal subjects, 0.51 +/- 0.05 and 0.72 +/- 0.11; cirrhotic patients with hepatopetal portal blood flow (n = 167), 0.64 +/- 0.08 and 1.03 +/- 0.24; cirrhotic patients with hepatofugal portal flow (n = 3), 0.74 +/- 0.08 and 1.27 +/- 0.08; cirrhotic patients with portal vein thrombosis (n = 9), 0.74 +/- 0.08 and 1.36 +/- 0.34; patients with noncirrhotic obstruction of the portal system (n = 7), 0.69 +/- 0.11 and 1.16 +/- 0.28; cirrhotic patients with surgical decompression of splenic vein system (n = 21), 0.54 +/- 0.07 and 0.76 +/- 0.15; patients with liver transplantation (n = 31), 0.50 +/- 0.08 and 0.70 +/- 0.15. Both RI and PI were significantly higher in cirrhotic patients with hepatopetal portal flow compared with controls (P < .0001), and even higher in cirrhotic patients with portal vein thrombosis (P < .004 and P < .001 in comparison with RI and PI values of cirrhotic patients). In patients with noncirrhotic portal vein thrombosis, splenic impedance indices were higher than those in controls (RI and PI P < .0001). Cirrhotic patients who underwent surgery for the therapy of portal hypertension showed splenic impedance indices significantly decreased compared with other cirrhotic patients (RI and PI P < .0001). In patients who underwent liver transplantation, splenic impedance indices were the same as those in controls. In 23 of the 52 patients surgically treated (surgical shunt or liver transplantation), impedance indices were evaluated both before and after surgical treatment. All these patients showed a decrease in splenic impedance indices (RI and PI, P < .0001) after surgical treatment. RI and PI values were higher in patients with large esophageal varices as compared with patients without or with small varices (P < .02 and P < .01). RI and PI values were not related to age, mean arterial pressure, sex, Child-Turcotte-Pugh score, presence of ascites, or cause. A significant correlation was found between splenic impedance indices and portal resistance as evaluated by hepatic vein catheterization (r = .80, P < .001 for RI values; r = .87, P < .001 for PI values). In conclusion, this study shows that splenic impedance indices are increased in cirrhotic patients, and seems to demonstrate that in patients with cirrhosis these indices reflect portal vein blood flow resistance.

Implication of laparoscopy and peritoneal cytology in the staging of early pancreatic cancer.

Staging of pancreatic cancer still represents a challenge for surgeons involved in this field. Diagnostic methods of radiological imaging used routinely (CT, NMR, angiography) may understage this neoplasm. In fact, the presence of peritoneal or subglissonian hepatic micrometastases (< 2 cm) is a frequent surprise at laparotomy and forces the surgeon to use a palliative procedure. Actually this policy has not to be followed because the possibility to perform non-surgical palliation of jaundice or pain respectively by percutaneous radiological stent insertion and celiac alcoholization. In this viewpoint, preoperative staging has acquired an important role for a correct treatment, be it surgical or medical. Laparoscopy allows it to overcome the understaging produced by the more common diagnostic means, with the possibility to view directly the celomatic space and the surface of the abdominal viscera; moreover, during this procedure it is possible to perform a peritoneal washing to obtain other information about the cancer stage. In our experience, 56 patients were judged as resectable by radiologic methods; 31 were excluded from surgery by laparoscopy; 10 of the remaining 25 cases were submitted to radical resection. The operative resectability rate resulted in 40%, against 18% in cases where we submitted to surgery all the patients. Seven patients underwent peritoneal washing, always with a negative result; all were submitted to surgery and radically resected. In our opinion, laparoscopy and peritoneal washing represent useful tools in the staging of patients affected by pancreatic cancer.

Pancreatic cancer and retroperitoneal neural tissue invasion. Its implication for survival following radical surgery.

To analyze the implication of retroperitoneal perineural lymphatic infiltration (rpli) for the survival of patients affected by exocrine pancreatic cancer, we considered 17 cases which underwent radical resection at our Institute from 1980 to 1993. Histology of specimens showed an rpli in 15 cases, without any correlation between this anatomopathologic aspect and the neoplasm size or the presence of lymph node metastases. The 2 patients without rpli are both alive and have been free from disease during a follow-up period of more than 5 years. In the group of 15 patients with positive rpli, 3 (21.4%) have remained free from disease (2 alive and 1 dead for other reason). Eleven remained with disease (1 is alive and 10 have died). One died in the postoperative period and could not be included in the evaluation. These observations have led the surgeon to consider the necessity, during resection, of an accurate dissection not only of the regional lymph nodes but also of the retropancreatic tissue and the neural structures present in this area. This approach may lead to a more correct staging of the neoplasia, a better radical surgery and perhaps a longer survival. Moreover it may represent an important marker for an adjuvant protocol of chemotherapy and/or radiotherapy.

[The palliative treatment of hepatocarcinoma: chemoembolization vs. the combination of tamoxifen plus beta-interferon]. / Il trattamento palliativo dell'epatocarcinoma: la chemoembolizzazione vs l'associazione tamoxifene più beta-interferon.

Clinical and experimental data show that beta-IFN enhances the effect of tamoxifen on advanced breast cancer. There is a similarity between breast and liver as far as the proliferating effect on normal and neoplastic tissue of estrogen and progestin receptors is concerned. The authors tested this pharmacological association in unresectable liver neoplasms. They considered 76 (not randomized) patients affected with HCC; 38 were treated by trans-arterial chemoembolization (TACE) and 38 to beta-INF and tamoxifen (the 2 groups were comparable according to age, sex, Child-Pugh score, Okuda and TNM stages, cirrhosis etiology). The treatment response (positive when a tumor diameter decreased or stabilization was observed) was similar in the two groups; in the TACE group, the presence of a peritumoral capsula had a significant influence on survival (p < 0.02); on the other hand, in the patients treated with beta-INF and tamoxifen important factors for a better prognosis were the TNM stage (I and II, p < 0.02) and a symptom-free condition (p < 0.04). The authors believe the beta-INF and tamoxifen treatment could represent an effective alternative in the management of unresectable HCC. A better knowledge of the presence and meaning of estrogen and progestin receptors in the neoplastic tissue may allow a better selection of patients.

[Reoperation in differentiated carcinoma of the thyroid gland]. / Reinterventi per carcinoma differenziato della tiroide.

A series of 112 patients reoperated on for differentiated thyroid cancer is analyzed; 60 patients (38 with papillary and 22 with follicular cancer) underwent ex-principio to completion of a non total thyroidectomy and 52 (37 with papillary and 15 with follicular cancer) to repeat surgery for local relapse. At a mean follow-up of 8.7 years, all the 38 patients with papillary cancer reoperated on for completion are alive and disease-free, while of those with follicular cancer 4 are dead, 2 are alive with carcinoma and 16 (72.7%) are disease free. A reoperation for relapse was performed on the thyroid in 11, on the thyroid and nodes in 23 patients (all had initially received partial thyroidectomy), and on nodes alone in 28 patients. At a mean follow-up of 10.2 years, 20 patients (54%) with papillary and 7 (46.6%) with follicular cancer are alive and disease-free, 8 patients with papillary and 1 with follicular cancer are alive with disease and the remainder are dead due to the tumour. Although there is no sure evidence that total thyroidectomy provides higher survival and fewer recurrences, since many factors, predominantly age influence the prognosis, total thyroidectomy is recommended as a minimal procedure to avoid less safe and less radical subsequent reoperation.

[The role of laparoscopy and peritoneal cytology in the preoperative staging of pancreatic carcinoma]. / Il ruolo della laparoscopia e della citologia peritoneale nella stadiazione pre-operatoria del carcinoma pancreatico.

The staging of pancreatic cancer still represents a challenge for surgeons involved in this field; radiological diagnostic methods used routinely (CT, NMR, angiography) may under-estimate this neoplasm; in fact, the presence of peritoneal or subglissonian hepatic micrometastasis (< 2 cm) is a frequent surprise at laparotomy and force the surgeon to undertake a palliative procedure. This policy need not be followed because it is possible to perform non-surgical palliation of jaundice or pain respectively by percutaneous radiological stent insertion and coeliac alcoholisation. Pre-operative staging thus acquires an important role in the correct treatment, surgical or medical. Laparoscopy allows us to overcome the understaging of the more common diagnostic methods and view directly the coelomatic space and the surface of the abdominal viscera; moreover during this procedure it is possible to perform a peritoneal wash to obtain other information on the cancer stage. We judged 56 patients by radiological diagnosis; 31 were excluded from surgery by laparoscopy; 10 of the other 25 cases were submitted to radical resection. The resectability operative rate was 40%, compared with 18% if we had submitted patients to surgery. Several patients underwent peritoneal wash, always with negative results; all were submitted to surgery and radically resected. In our opinion, laparoscopy and peritoneal wash represent useful tools in the staging of patients affected with pancreatic cancer.

Routine determination of biliary lipid composition with the entero-test.

A simple method for the assay of biliary lipids was used for routine determination of biliary cholesterol saturation index (CSI) in 17 healthy subjects, 40 untreated patients with radiolucent gallstones and 21 gallstone patients treated with ursodiol. The method is based on collection of bile with the Entero-Test, a device for easy sampling of gastrointestinal contents. The procedure was easy to perform and well accepted by the patients. Both CSI and the cholesterol content of bile were higher in untreated gallstone patients than in controls, and were significantly lower in treated than in untreated patients. Normal CSI was found in 35% of untreated gallstone patients, while 24% of healthy subjects had supersaturated bile. Supersaturated bile was still present in 14% of ursodeoxycholic acid treated patients, suggesting inefficacy of therapy. These results demonstrate the possibility of performing easy, routine determination of biliary lipid composition, which can yield useful information for the management of gallstone patients.

[Isolated rupture of the right hemidiaphragm with complete herniation of the liver into the thorax. Considerations of diagnosis and therapy]. / Rottura isolata dell'emidiaframma destro con erniazione completa del fegato in torace. Considerazioni sulla diagnosi e sul trattamento.

The Authors report a case of right diaphragmatic hernia due to road-traffic accident. They discuss the problems of early diagnosis because it is delayed for multiple associated lesions or a low index of suspicion. The ratio of laceration of the left side to that of the right is twenty to one. The clinical and diagnostic data best able to lead to a rapid preoperative diagnosis are considered. The Authors recommended early operative treatment and the thoracic approach; thoracoabdominal incisions are more suitable whenever abdominal lesions are coexisting. The Authors stress the use of safety belts with three point fastener which have significantly decreases cranial and abdominal lesions, particularly if associated with two rolls up.

Dermatan sulphate: a safe approach to prevention of postoperative deep vein thrombosis.

To assess the efficacy and safety of dermatan sulphate (MF 701) in preventing postoperative deep vein thrombosis (DVT), 324 patients aged 40 years or over undergoing elective major general surgical operations were included in a randomized trial comparing MF 701 (100 mg intramuscularly once a day) with unfractionated calcium heparin (UFH, 5000 units subcutaneously three times daily). Both treatments were initiated before operation and continued until discharge. In all, 316 patients were included in the analysis (MF 701, 157; UFH, 159). Serial impedance plethysmography was performed in all patients; a 125I-radiolabelled fibrinogen uptake test was added to impedance plethysmography in a randomized subsample of 62 patients (MF 701, 28; UFH, 34). Positivity in either test was confirmed where possible by venography. DVT was diagnosed by venography or, when this could not be performed, by positivity of either impedance plethysmography or fibrinogen uptake test. The incidence of DVT was 3.1 per cent (patients receiving MF 701) and 1.6 per cent (those receiving UFH) in patients undergoing impedance plethysmography alone, and 7.1 and 11.8 per cent, respectively, in those undergoing both impedance plethysmography and fibrinogen uptake test; in neither case was the difference between treatments statistically significant. There were five in-hospital deaths, two in patients receiving MF 701 and three in patients on UFH. The incidence of clinically overt haemorrhage was 5.7 per cent in patients on MF 701 and 17.6 per cent in those on UFH (P less than 0.01). Postoperative transfusions and reoperations due to bleeding were significantly less frequent in patients receiving MF 701. Mortality rates at 3 months were similar for the two treatment groups. Compared with standard prophylaxis using UFH, MF 701 showed a similar efficacy with a significantly greater safety.

Selective variceal decompression and its role relative to other therapies.

Seventy patients, selected from 265 patients with proved variceal bleeding, underwent a distal splenorenal shunt (DSRS) procedure with or without splenopancreatic disconnection (SPD). Alcoholic cirrhosis was the cause of portal hypertension in 57% of the patients. The operative mortality was 13% (Child's classes A and B 2%, class C 66%). Despite fewer varices in all of the patients, variceal rebleeding and death occurred in one patient (2%). Late portal perfusion was observed in 91% of the patients, with worsening in 23%, compared with the preoperative study. Persistent hepatocyte necrosis and incomplete SPD were the most significant prognostic factors for decreased perfusion (presence and absence of necrosis, 38% and 12%, respectively; DSRS and DSRS with SPD, 43% and 12%, respectively). SPD also decreased ongoing hepatocyte damage. Post-shunt encephalopathy was clinically evident in 7% of the patients, but after electroencephalographic evaluation, it increased to 24.6%. Significant factors in its development included decreased portal perfusion (62% versus 14%), active hepatitis (48% versus 17%), and incomplete SPD (43% versus 14%). The higher late liver-related mortality was associated with a lack of or decreased portal perfusion and the absence of SPD.

The role of the leukocyte adherence inhibition (LAI), CA 19-9, and tissue polypeptide antigen (TPA) tests in the diagnosis of pancreatic cancer.

The leukocyte adherence inhibition (LAI) assay measures host cell-mediated tumor immunity. The original test used by Halliday and Miller was modified by substituting tissue extracts with purified tumor antigens (gastrointestinal cancer antigen [GICA]) with the aim of reducing false-positive results in the diagnosis of patients with early pancreatic cancer. By our modified technique, the LAI assay identified four of five pancreatic cancers at an early stage and gave only one false-positive result in 16, showing a sensitivity of 80% and a specificity of 94%. Later stages of the disease responded poorly on the test. These results were significantly better than those by the CA 19-9 and tissue polypeptide antigen (TPA) tests. Should our findings be confirmed in larger material over a longer follow-up period, the LAI test could be proposed as a useful tool in the early diagnosis of pancreatic cancer.

[The L.A.I. test and tumor markers (Ca 19-9 and TPA) in the diagnosis of pancreatic carcinoma]. / L.A.I. test e markers tumorali (Ca 19,9 e TPA) nella diagnosi del carcinoma pancreatico.

A particular cell-mediated immune response is tested in this work: the leukocyte adherence inhibition (L.A.I.) in the presence of organ tumor antigens. Forty-two patients suspected of having pancreatic cancer were submitted to the L.A.I. test and Ca 19.9 and TPA determination. The diagnosis of pancreatic cancer was eventually surgically confirmed and staged in 30 patients. The most important features of the L.A.I. test were good specificity (94%) and the ability to diagnose stage I cancers (3/4 cases, 75%), while the other markers are more likely to diagnose more advanced stages. The L.A.I. test seems to be also useful during the follow-up period since its positivity may even be some months previous to the clinical symptoms. During follow-up the L.A.I. test proved useful in supervising the neoplastic disease course from the moment of relapse to advanced clinical symptoms.

[Benign Castleman's lymphoma. Remarks on 2 cases]. / Il linfoma benigno di Castleman. Considerazioni su due casi.

Two personally observed cases of Castleman's benign lymphoma of the hyaline vascular type located in the mediastinum are described. The stages in the development of our knowledge of this tumour are traced and the various aetiopathogenic theories discussed. The difficulty of preoperative diagnosis is emphasised while the potential predictive value of calcifications combined with hypervascularization in an asymptomatic mass usually in the mediastinum and revealed by CT is pointed out.

Thrombocytopenia in liver cirrhosis complicated by variceal haemorrhage: lack of increase in platelet count after spleno renal distal shunt.

10 patients with liver cirrhosis (LC) and previous variceal bleeding have been studied. Platelet count was markedly depressed. Giant platelet percentage (MTI) was significantly increased, reflecting bone marrow compensatory hyperactivity. Platelet associated IgG (PAIgG) was elevated. Such elevation, however, was inconstant and did not correlate with platelet count. Beta-thromboglobulin was markedly increased when referred to circulating platelet number, but its level did not accurately reflect platelet activation, because of decreased liver cell function. Platelet Factor 4 was always zero, thus confirming that high values of this protein represent only a laboratory artifact, due to platelet activation in vitro. 5 patients underwent spleno renal distal shunt, which transiently improved hypersplenism only in one case. Despite this, MTI became perfectly normal in all patients, suggesting a decrease in the thrombopoietic stimulus. PAIgG dramatically fell in the two patients with the highest pre-operative values. Since thrombocytopenia persisted, the non-specific nature of PAIgG in LC seems to be further supported.