Surgical therapy for undifferentiated (embryonal) sarcomas of the liver in adults.

Undifferentiated (embryonal) sarcoma of the liver is a rare malignant mesenchymal tumor with a poor prognosis. Thirty cases worldwide have been reported over the last 40 years. The absence of specific symptoms, the rapid tumor growth, the normality of the common tumoral markers and the consequential delay in the diagnosis, often allow a significant enlargement of the hepatic mass. Three patients ages 15, 25, and 60 were admitted to our department with such a tumor. In spite of the large dimensions of the neoplasms, all underwent a right hepatectomy without any major surgical complications. Two of them died due to tumor recurrence after 10 and 67 months, respectively. The one case remaining is alive and disease free 62 months postoperatively. The latter one was the only case where a complete tumoral capsule was found in the resected specimen. Surgery is strongly recommended for every case with evidence of a liver-confined tumor even if it is large.

[Portosystemic shunts in the treatment of bleeding esophageal varices in cirrhotic patients: between sclerotherapy and transplantation]. / Gli interventi di derivazione porto-sistemica nel trattamento dell'emorragia da varici nel paziente cirrotico: tra scleroterapia e trapianto.

In view of the proven efficacy of endoscopic sclerotherapy and the even improving results of liver transplantation, the present role of porto-systemic shunt should be reconsidered. From 1986 (when our liver transplant program began), to March 1994, 59 cirrhotic patients (males = 40, females = 19, mean age 53.17 +/- 12.04) underwent a porto-systemic shunt, 22 under emergency conditions and 37 in an elective setting. Patients were subdivided according to age, emergency or elective surgery, type of operation, and liver function. In the emergency procedures previous sclerotherapy and time between admission and surgery were also considered in the assessment. Mean follow-up was 46.49 +/- 31.48 months. Overall 5-year actuarial survival was 62.5%. In the emergency porto-systemic shunts the worst short-term results were obtained in patients over 55 years of age (p < 0.05) and when operations were performed within the first 24 hours after admission (p < 0.005). Long-term survival was not significantly influenced by the variables considered although patients over 55 years of age and patients with reduced liver function (Child B and C) seemed to have a more dismal outcome. Those patients under 55 years of age, with no portal thrombosis, considered as potential liver transplant candidates, had a better short-term survival rate (p < 0.05) than that of the rest of the patient population studied, mainly because of the better outcome after emergency surgery. Our data confirm the efficacy of porto-systemic shunt procedures in preserving the patient from variceal bleeding. They have a definite role in the complex treatment strategy of portal hypertension, and they must not be considered only a rescue procedure. However, liver transplantation remains the best option to resolve both portal hypertension and the underlying liver disease.

Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.

BACKGROUND: It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. METHODS: We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. RESULTS: Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. CONCLUSIONS: An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.

Surgery for esophageal achalasia. long-term results with three different techniques.

BACKGROUND/AIMS: In surgery for achalasia, the length of the myotomy and the opportunity of associating an antireflux procedure are still debated. Prospective and comparative studies on different techniques are few. The aims of this work is to compare the long term results of three different techniques successively adopted by the same surgical group. MATERIALS AND METHODS: Between January 1955 and December 1991, 185 achalasic patients were submitted to myotomy by using in temporal sequence three different techniques. The first technique utilized (1955-1972) was a long esophagogastric abdominal myotomy (83 patients), secondly (1973-1978) a limited transthoracic myotomy (30 patients) and at last (1979-1991) a long esophagogastric abdominal myotomy associated to the Dor gastroplasty (72 patients). Since 1972, patients were prospectively followed up according to a protocol which included a clinical interview, x-rays, manometry and endoscopy at given dates. Post-operative esophagogastric transit and gastro-esophageal reflux were assessed to verify the therapeutical outcome. Results obtained with the three different techniques were analyzed and compared by using the actuarial Kaplan-Meier curves. RESULTS: The mean follow up was 193.3 months for the patient group that underwent abdominal myotomy (62/83 patients), 137.3 months for the thoracic myotomy group (30/30 patients) and 86.9 months for the abdominal myotomy plus Dor gastroplasty group (69/72 patients). Long-term results in the abdominal myotomy and in the thoracic myotomy groups were respectively poor in 51.6% and in 46.6% of patients. Major causes of failure were insufficient myotomy (6.5%), periesophageal scarring (9.6%) and reflux esophagitis (22.6%) for the abdominal myotomy group; insufficient myotomy (20%) and reflux esophagitis (23%) for the thoracic myotomy group. In the abdominal myotomy plus Dor gastroplasty group long-term results were excellent or good in 87% of patients and poor in 13%. Reflux esophagitis (10% of cases) was the principal cause of failure. CONCLUSIONS: The comparison of the actuarial curves shows a significantly better long term outcome for the abdominal myotomy plus Dor antireflux procedure than for the abdominal myotomy (p = 0.01) and for the thoracic myotomy (p = 0.002) techniques.

Transfer factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy.

The rationale for using transfer factor (TF) in lung cancer patients is that the possibility of improving their cell-mediated immunity to tumour associated antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non-small cell lung cancer (NSCLC) resected patients were monthly treated with TF, extracted from the lymphocytes of blood bank donors. In the same period, 257 NSCLC resected patients were considered as non-treated controls. The survival rates of the TF treated group appear significantly improved both for patients in stages 3a and 3b, and patients with histological subtype "large cell carcinoma" (P < 0.02). Survival of TF treated patients is also significantly higher (P < 0.02) for patients with lymph node involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.

Ruptured hepatocellular carcinoma: an important cause of spontaneous haemoperitoneum in Italy.

OBJECTIVE: To evaluate the incidence of rupture of the tumour with intraperitoneal bleeding in a series of patients with hepatocellular carcinoma and its relative incidence as a cause of spontaneous haemoperitoneum, and to evaluate the results of the surgical treatment of a consecutive series of patients who presented with spontaneous haemoperitoneum caused by ruptured hepatoma. DESIGN: Retrospective study. SETTING: University hospital, Italy. SUBJECTS: 8 patients whose hepatocellular carcinoma ruptured (out of a total of 518) and caused spontaneous haemoperitoneum, and 34 patients who were admitted with spontaneous haemoperitoneum. INTERVENTIONS: Seven hepatic resections; in one case direct haemostasis was attempted because of the poor hepatic reserve. RESULTS: Rupture of the tumour with intraperitoneal bleeding occurred in 8/518 (2%) of cases of hepatocellular carcinoma. Ruptured hepatocellular carcinoma was the second most common cause of spontaneous haemoperitoneum (8/34; 24%), after gynaecological diseases (15/34; 44%). Of the 7 patients who presented with ruptured hepatocellular carcinoma and were treated by hepatic resection, 3 are alive (one with a recurrent disease) after a mean follow-up of six months (range 3 to 12 months) and 4 died of carcinomatosis within 12 months. The patient for whom resection was not feasible died immediately postoperatively of irreversible shock. CONCLUSIONS: Rupture of hepatocellular carcinoma is a relatively common cause of spontaneous haemoperitoneum. Diagnosis at the onset of symptoms has important therapeutic implications: as the results of surgical treatment are unsatisfactory, other procedures with the limited goal of achieving satisfactory haemostasis can be considered if the hepatocellular carcinoma has been diagnosed.

Liver resection without blood transfusion.

A retrospective study was carried out of 522 elective liver resections to determine the impact of blood transfusion on the immediate postoperative outcome and on long-term survival. The number of liver resections without transfusion has increased in recent years, as a result of improvement in surgical technique with less blood loss during operation and more careful choice of the timing of transfusion. In resections carried out in the past 5 years, the indication for intraoperative transfusion was restricted and the decision was made jointly by the surgeon and anaesthetist, and in any case only if the haematocrit was below 25 per cent. Of resections carried out in the past 2 years, 59 per cent did not require intraoperative transfusion. Postoperative deaths and complications were related to blood transfusion, particularly in patients with cirrhosis, in whom stepwise logistic regression analysis showed that transfusion was the only factor that correlated significantly with complications. Transfusion also affected the long-term survival of patients operated on for hepatocellular carcinoma and colorectal carcinoma metastases in univariate analysis and was the only factor shown by multivariate analysis to correlate with survival for hepatocellular carcinoma in patients with cirrhosis.

The role of tumor markers in the diagnosis of hepatocellular carcinoma, with special reference to the des-gamma-carboxy prothrombin.

The assessment of new and more sensitive serum markers for hepatocellular carcinoma (HCC) represents a useful contribution to the diagnosis of small liver tumors, still amenable by surgery. We evaluated the efficacy of the tumor markers proposed during recent years for the study of HCC: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), serum ferritin (SF), tissue polypeptide antigen (TPA), and, finally, the more recently proposed des-gamma-carboxy prothrombin (DCP). Of the 227 patients included in this retrospective study, 111 had HCC, and 85 of these were also cirrhotic. The remaining 116 patients, considered as the control group, included 23 patients with liver metastases from colorectal cancer, 26 with benign hepatic lesions, 20 with tumors other than HCC without hepatic metastases, and 47 with other liver diseases. For each single tumor marker, the sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and Younden index were assessed. AFP and DCP proved to be the most effective, with sensitivity, specificity, and diagnostic accuracy of 54.9%, 97.4%, and 76.6% and of 53.3%, 88.1%, and 71.1%, respectively. The same parameters evaluated for combined use of the two markers were 74.2%, 87.2%, and 80.9%, respectively. Analysis of the other markers produced no further significant contribution. Of the 111 patients with HCC, 35 (33.3%) were positive for both AFP and DCP, 43 (41%) were positive for one of them, and 27 (25.7%) were completely negative. In the 44 patients who underwent liver resection or transplantation, DCP correlated significantly with the histological presence of microvascular thrombosis, the major factor determining long-term survival after curative surgery. As a tumor marker for HCC, DCP is at least as effective as AFP; the combined use of AFP and DCP significantly improves the chances of identifying HCC by serodiagnosis.

Duodenogastric and non acid gastro-oesophageal reflux in patients with reflux oesophagitis.

BACKGROUND/AIM: The role and the identification criteria of non acid gastro-oesophageal reflux (GOR) are still debated. Moreover, the relationship between nonacid GOR and gastric alkalinizations, particularly if secondary to duodeno-gastric reflux is yet to be defined. MATERIALS AND METHODS: One hundred and forty one patients affected by GORD symptoms and oesophagitis entered the study. Oesophagitis was divided into four categories, according to a modified Savary and Miller classification. Acid (pH<4), alkalacid (47), alkaline (pH>7) GOR and duodenogastric reflux were measured by means of ambulatory three channel esophago-gastric pH monitoring with a combined analysis of the pH traces recorded in the oesophagus fundus and antrum. RESULTS: Total time percentage (T%) of acid GOR was significantly greater in patients than in healthy volunteers (HV) and between groups of patients in direct relation with the severity of the oesophagitis. Alkaline GOR was hardly detectable in every class of esophagitis. Alkalacid GOR increased with the grade of severeness of oesophagitis. Alkalacid GOR occurred prevalently in the postprandial period; it was only 8% of the time in patients with mild reflux oesophagitis and even less in patients with moderate or severe oesophagitis. The 24 hr total time percentage of duodenogastric reflux was similar in the patients and healthy volunteer groups. The frequency distribution in 0.1 intervals of fundic and antral pH samples showed a greater number of them in the acid range (0.8-1.2) in the patients than in healthy volunteer group (0.00067) samples was similar in patients and in healthy volunteers. CONCLUSIONS: Our findings demonstrate that alkaline GOR is rare in GORD patients and that non acid GOR has a minor role in the pathophysiology of reflux esophagitis.

Fatal necrotizing pancreatitis caused by hepatitis B virus infection in a liver transplant recipient.

A 32-year-old man who had undergone liver transplantation for fulminant hepatitis due to HBV infection developed fatal acute necrotizing pancreatitis on the 60th post-transplant day, while showing signs of intense viral replication. Immunohistochemistry and in situ hybridization of the pancreas following autopsy showed the presence of HBsAG and HBV-DNA in the cytoplasm of acinar cells, together with the picture of necrotizing pancreatitis. Clinical and histological features seem to indicate that pancreatitis was directly caused by HBV infection.

Etiologic factors and clinical presentation of hepatocellular carcinoma. Differences between cirrhotic and noncirrhotic Italian patients.

BACKGROUND: It is not known whether the prevalence of hepatocarcinogenic factors differs between cirrhotic and noncirrhotic patients with hepatocellular carcinoma (HCC) or whether the clinical presentation of HCC in these two groups differs. METHODS: The prevalence of the putative etiologic factors of HCC and its clinical presentation in 373 patients with cirrhosis and 102 without cirrhosis seen from 1981 to 1992 were evaluated. RESULTS: Hepatitis C virus infection (76 vs. 48%, P = 0.003) and both current (22.5 vs. 10%, P = 0.007) and past (50.5 vs. 34.5%, P = 0.045) hepatitis B virus infections were more common in cirrhotic than in noncirrhotic patients with HCC. The absence of exposure to both viruses was much less frequent in the former (7 vs. 40%, P < 0.001). Heavy alcohol intake prevailed in patients with cirrhosis (30 vs. 16.5%, P = 0.01). Alpha-fetoprotein elevation was more common in cirrhotic patients (63% vs. 31%, P < 0.001); however, the prevalence of diagnostic (> 400 ng/ml) levels did not differ significantly (24 vs. 17%) between the two groups. Extrahepatic extension of HCC was more common in noncirrhotic patients (20.5 vs. 6.5%, P < 0.001) and its independent predictors were poor cancer differentiation and absence of cirrhosis. "Asymptomatic" cancers were more frequently encountered with cirrhosis. Abdominal pain was the most common presenting symptom in both groups. Signs of hepatic decompensation prevailed in cirrhotic patients, whereas a "toxic syndrome" dominated the clinical picture of the noncirrhotic patients. CONCLUSIONS: Hepatitis viruses are associated more with carcinogenesis of the cirrhotic than of the noncirrhotic liver. Alpha-fetoprotein is not a sensitive neoplastic marker, particularly in noncirrhotic patients. In the latter, HCC appears more advanced at diagnosis and symptoms of neoplastic toxicity are prominent.

[Primary carcinoma of the middle and distal third of the common bile duct, diagnosis, treatment and results]. / Carcinoma primitivo del terzo mediale e distale della via biliare principale, diagnosi, trattamento e risultati.

The authors present a series of 21 patients with primary carcinoma of the middle and distal third of the extrahepatic biliary tract observed between 1981 and 1994. Indications and limits of the adopted diagnostic protocol and the selection criteria of the patients, identified by evaluating the preoperative resecability, are discussed. The indications for therapy considered the location of the neoplasia and the definitive staging obtained with the intraoperative ultrasonography and the histopathological examination. Seventy six percent of the operations were curative and the mean survival was 40 months range 13-120 mth for patients with tumor of the middle third and of 33 months range 10-133 mth for patients with tumor of the distal third. Survival results in patients who underwent palliative surgery seem to be similar to those obtained with non surgical palliative methods.

Endoscopy versus endoscopic ultrasonography in staging reflux esophagitis.

Precise staging of reflux esophagitis is very important for therapeutic decisions; in fact, chronic gastroesophageal reflux may cause transmural inflammation that leads to fibrosis with loss of esophageal wall compliance. In reflux esophagitis, endoscopic stating is limited to mucosal injury, while endoscopic ultrasonography (EUS) is able to visualize changes in the layer structure and localized or diffuse thickenings of the esophageal wall. In order to evaluate the usefulness of EUS in reflux esophagitis, a prospective study of 31 patients and ten normal subjects was performed. Endoscopic reflux esophagitis was staged as: E1 (erythema, n = 7), E2 (erosions, n = 13), E3 (ulcers, n = 11). EUS findings were recorded and evaluated at five different levels, starting from the gastroesophageal junction, using a quantitative method, the center line method. With this method, the sectorial and mean thickness, and area were calculated for each level. There was a significant difference between patients with reflux esophagitis and normal subjects in our study. E3 patients showed a significant upward involvement of the wall far from the visible lesions. Mild esophagitis may also cause esophageal wall thickening, involving even the entire wall. There was no correlation between the onset time of symptoms and the degree of thickening. In conclusion, EUS seems to be an important supplement to endoscopy in staging reflux esophagitis, as the progression of the inflammation is not related to the endoscopic findings.

[The laparoscopic treatment of functional esophageal diseases. Preliminary experience with Nissen's intervention and Heller-Dor's intervention]. / Trattamento laparoscopico delle malattie funzionali dell'esofago. Esperienza preliminare con l'intervento di Nissen e con l'intervento di Heller-Dor.

UNLABELLED: Aim of the study is to analyse the preliminary results that we obtained with laparoscopic surgery for esophageal functional diseases. Twenty four patients between April 1992 and December 1993 underwent laparoscopic procedures for gastroesophageal reflux disease and achalasia, respecting the same principles adopted for the traditional surgery. A 360 degrees Nissen fundoplication modified according to DeMeester was performed in 12 patients with severe cardial incontinence or reducible gastric hiatal hernia. The 12 patients with achalasia underwent esophagogastric myotomy associated with a Dor hemifundoplication. Myotomy and gastroplasty were performed under manometric control. The mortality was zero in both techniques. All Nissen procedures were completed laparoscopically, while 2 Heller-Dor were converted to the laparotomy version. The mean duration time of the procedure has been 190' for the Nissen operation and 230' for the Heller-Dor. In one patient submitted to the antireflux gastroplasty occurred a pleural effusion. The short term results (mean follow-up 6 months) of the laparoscopic procedures were comparable with the traditional laparotomy operation. IN CONCLUSION: the two procedures are feasible via laparoscopy; the intraoperative manometry is useful for the Heller-Dor operation; the laparoscopic approach for functional diseases must be considered experimental until were obtained satisfactory long term results.

Functional outcome in handsewn versus stapled ileal pouch-anal anastomosis.

Eighty-eight of 119 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were evaluated. Forty patients had a handsewn anastomosis (Hs) with mucosectomy, and 48 had a stapled anastomosis (St). In each patient, we evaluated operative, morphologic, functional, and manometric features. The results in the Hs and St groups were similar when the anastomosis was within 1 cm of the dentate line. In particular, there was no correlation between the type of anastomosis and the number of bowel movements in a 24-hour period, the presence of the urge to defecate, and the use of antidiarrheal drugs. Leakage was significantly higher in the Hs group, even when the anastomosis was less than 1 cm from the dentate line. Pouchitis was more frequent in the Hs group, and, within this group, among those with a short distance between the anastomosis and the dentate line. No correlations were found between the presence of columnar epithelium or active colitis in the mucosa below the anastomosis, the functional outcomes, and the incidence of pouchitis.

[Acute inflammation of ileal reservoir after restorative ileoanal anastomosis]. / Infiammazione acuta del reservoir ileale dopo intervento di ileo-ano anastomosi.

Ileo-anal anastomosis (IAA) is a suitable surgical treatment for selected patients with ulcerative colitis or familial adenomatous polyposis. Acute inflammation of the ileal reservoir (pouchitis) is the most frequent late complication and is characterized by endoscopic and histological changes of acute inflammation similar to ulcerative colitis with abdominal and sometimes systemic symptoms. Between May 1984 and April 1993, 160 patients (103 male and 57 female) aged between 7 and 64 years (mean age 32.6) underwent IAA; twenty of these for familial adenomatous polyposis, 138 for ulcerative colitis and 2 for indeterminate colitis. After a mean follow-up of 41.8 months (range 1-108), 138 patients (86.3%) were symptoms free and twenty-two (16 male and 6 female-13.7%) who underwent IAA for ulcerative colitis, had pouchitis. Clinical, biochemical, endoscopic and histologic findings suggest pouchitis as a chronic recurrent disease similar to inflammatory bowel disease. In conclusion, the etiopathology of this new entity is unknown. Bacterial overgrowth is one of the most popular hypothesis, but the onset of the acute inflammation observed by us only in patients with previous ulcerative colitis and in some cases during the period of protective ileostomy suggests a multifactorial pathogenesis.