Submucosal endoscopic tumor resection for subepithelial tumors in the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Resection of submucosal tumors by means of endoscopy has been reported using a variety of techniques, but cannot be performed safely in tumors originating from the muscularis propria. Using the submucosal tunnel created by the technique of peroral endoscopic myotomy (POEM), we report the first series describing the new technique of submucosal endoscopic tumor resection (SET) for tumors of the esophagus and cardia. PATIENTS AND METHODS: SET was attempted in nine consecutive patients with tumors (size >2cm) of either the esophagus or cardia with clinical indications for lesion removal. Following creation of a submucosal tunnel from 5 cm above the tumor, as described previously, the tumor was dissected from the overlying mucosa/submucosa and then carefully removed from the muscular layer using triangle-tip and insulated-tip knives. Following specimen retrieval through the tunnel, the orifice was closed by clips. RESULTS: Of the nine patients, two had tumors that were too large (60 mm and 75 mm, respectively) to allow safe removal due to loss of endoscopic overview. All remaining tumors (maximal tumor extension 12-30 mm) could be resected safely using this method. No complications occurred and follow-up was unremarkable. On histology, all tumors were resected completely (one gastrointestinal stromal tumor, five leiomyomas). The technique had to be modified in one patient with an aberrant pancreas. CONCLUSIONS: SET is a promising new technique for selected submucosal tumors in the esophagus and cardia up to a size of 4 cm and should be studied further.

Diagnostic value of serum tumor markers in asymptomatic individuals.

PURPOSE: Tumor markers, particularly carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP), are widely used in oncology, either in monitoring patients with metastatic colorectal cancer (CEA) or surveillance of hepatocellular carcinoma (HCC/AFP). The objective of this study was to determine the diagnostic value of CEA, CA19-9 or AFP in asymptomatic individuals. METHODS: 12 asymptomatic individuals (6 males), with age range 55-82 years, referred to outpatient Gastroenterology- Oncology department for second opinion, with slightly elevated serum CEA (8 persons), CA19-9 (2 persons), and AFP (2 persons). The tumor markers were ordered from the primary practitioner or internist in order to avoid further specific examinations, such as colonoscopy. All individuals were totally asymptomatic. One of them had a known-history of 5-year surgically removed malignant pediculated sigmoid polyp and remained asymptomatic since then. RESULTS: After continuous and repeated meticulous examinations in all individuals, no specific pathology was found to explain the slightly elevated tumor markers. In one male (59 years) and one female (75 years) with slightly elevated CEA levels, 2 small colonic polyps were found, which were endoscopically removed. Repeated CEA levels 3 months later remained borderline high. During follow-up, 3 years after the discovery of slightly elevated tumor markers all individuals remained asymptomatic (positive predictive value / PPV 0%). CONCLUSION: Although further prospective studies are necessary, the preliminary results of this study showed that tumor markers are not useful for primary prevention of gastrointestinal malignancy. Moreover, slightly elevated tumor markers are confusing, leading to unnecessary examinations and stress from the individual's point of view.

Maintenance therapy for ulcerative colitis has no impact on changes in the extent of ulcerative colitis.

BACKGROUND AND AIM: Although the efficacy of maintenance remission therapy in ulcerative colitis (UC) has been proved in many studies, little is known about its possible effect on the extent of the disease. The aim of the present multicenter Belgian study was to evaluate the potential role of UC maintenance therapy on the colonic extension of the disease. MATERIALS AND METHODS: A total of 98 patients, 56 males, 42 females, mean age 52 years, range 22-82 years, from 12 medical centers in Belgium, with an acute exacerbation of well-established, endoscopically and histologically proven left-sided UC, were included. The colonic extension was endoscopically determined at the time of the initial diagnosis and at the actual flare-up. The mean duration of UC was 93+72 months, median was 84 months, and range was 3-372 months. Active smoking was reported in only 7% of patients, while the majority were no-smokers (63%) or ex-smokers (30%). The median colonic extension at the time of initial diagnosis was 25 cm, range 2-70 cm from the anal merge. Sixty-six percent of the patients had quiescent disease without flare-ups during last year. The χ(2)-test was used for statistical analysis. RESULTS: 29/98 (29.6%) patients had not used any maintenance therapy in the last 3 months before the actual exacerbation. The most commonly used maintenance therapy was 5-ASA (43%), while combined therapy with 5-ASA, corticosteroids or immunosuppresives (mainly azathioprine) in all possible combinations was reported by 29.6% of patients. The extent of UC had not changed in 50.7% and 51.7% of patients, respectively, with and without maintaining therapy (NS, p=0.99). Some degree of regression was observed in, respectively, 21.7% and 20.7% (NS, p=0.99), and some degree of extension in, respectively, 27.5% and 27.6% (NS, p=0.99). Furthermore, no relationship was found between changes in colonic extent and type of maintaining therapy, smoking habits or disease activity during the last year before the acute exacerbation. A tendency of beneficial effect of maintenance therapy on disease extent was observed in patients with continuous active disease of short duration. CONCLUSIONS: According to this multicenter study, maintenance remission therapy for left-sided UC was not found to have a statistically significant effect on colonic extension. Further long-term studies are necessary to confirm these results.

Upper gastrointestinal complaints as a consequence of thoracic spinal tumor.

A rare case of a 43-year-old male with chronic epigastric complaints and atypical diffuse osseous pain for two years, which were finally found to be caused by a benign thoracic spinal tumor (lipoma) and was successfully treated by neurosurgical resection, is presented. At three years follow-up postoperatively he remains completely asymptomatic. This report discusses the case and the potential pathophysiology of the patient's symptoms.

Status epilepticus as a manifestation of hepatic encephalopathy.

OBJECTIVES: Seizures have been described as a rare manifestation of hepatic encephalopathy. MATERIAL AND METHODS: We present a 54-year-old female, with 6-year history of decompensated, hepatitis B liver cirrhosis, admitted with generalized seizures. She reported a history of recurrent episodes of hepatic encephalopathy, spontaneous bacterial peritonitis, tense ascites and variceal hemorrhage. Neurologic examination revealed a comatose patient, without papilledema. Laboratory examinations were suitable with cirrhosis and mild renal failure. Blood gas examination revealed severe metabolic acidosis and hypoxemia. Plasma NH3+ levels upon admission were twice normal. Brain computed tomography and magnetic resonance imaging were normal. Electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy, grades III-IV. RESULTS: Status epilepticus was refractory to continuous antiepileptic treatment. However, it was resolved after 24-h therapy with lactulose. Blood NH3 levels were simultaneously normalized with clinical improvement. CONCLUSIONS: We consider the status epilepticus of our patient to be a rare manifestation of hepatic encephalopathy.

Palliative treatment of painful bone metastases from non-Hodgkin lymphoma with disodium pamidronate.

We report a case of a 72-year-old male, with a known history of non-Hodgkin lymphoma of the left tonsil for two years, histologically proved and successfully treated by radical surgical excision in combination with external radiotherapy. He presented with diffuse bone pain the last month, especially at the lower left ribs, which was found to be due to multiple osseous metastases by bone scintigraphy. The patient was initially treated by common analgesics and when the pain deteriorated he was administered 180 mg i.v. disodium pamidronate (AREDIA, Novartis Inc.). The patient showed excellent pain relief as well as dramatically improvement of WHO status and stopped the analgesics. An interesting point of our case was that the pain deteriorated again after a month and reduced soon after the re-administration of pamidronate, which was continued every month. So far, 10 months after the first pamidronate injection, our patient remains stable with excellent pain relief. Despite the absence of related data in the current literature, we consider the use of high dose pamidronate intravenous therapy safe and an effective method of palliative management of painful osseous metastases from non-Hodgkin lymphoma.

Is external palliative radiotherapy for gallbladder carcinoma effective?

BACKGROUND: Gallbladder carcinoma is characterized by delayed diagnosis, ineffective treatment and poor prognosis. Surgical resection has been thought to be the treatment of choice, while the role of radiotherapy as adjuvant or palliative treatment has not been fully clarified in the literature. PATIENT AND METHODS: We present the case of a 45-year-old female, with unresectable gallbladder carcinoma, grade IV, histologically diagnosed during laparotomy. The patient was treated with palliative intent with percutaneous transhepatic biliary drainage. Furthermore, she received external radiotherapy by (60)Co, using a three-field technique (anterior-posterior and right lateral). The total dose was 3,000 cGy in 10 fractions, with 300 cGy per fraction, 5 days weekly. RESULTS: The patient showed clinico-laboratory improvement and was discharged with a permanent percutaneous transhepatic endoprosthesis. During follow-up (10 and 12 months postirradiation), abdominal CTs showed no local extension of the tumor, while the patient had a good performance status. So far, 1 year after the diagnosis of gallbladder cancer she is still alive. CONCLUSIONS: External radiotherapy seems to be a safe and effective method of palliative management of gallbladder carcinoma. However, further studies are necessary to determine the role of radiotherapy in palliative or adjuvant treatment of gallbladder carcinoma.

Parasuicidal poisoning treated in a Greek medical ward: epidemiology and clinical experience.

OBJECTIVE: To study the epidemiology of acute poisoning patients presenting to an acute medical service ward in a Greek hospital between January 1998 and December 2000. DESIGN: Prospective case series. RESULTS: A total of 273 patients with self-poisoning were included in the study. This represented 3.8% of the overall admissions to the unit. The mean age of patients was 33, the most frequent age group being that aged 20-30 years (36.2% of total) with a male-to-female ratio of 1:1.97. Sixty per cent of patients was admitted within 4 h. Those from urban areas comprised 76.2% and 23.8% from rural areas. The most frequently ingested agents were psychopharmaceuticals (37.4%) and analgesics/anti-rheumatics (32.6%). Pesticides (7.7% of total) were most frequently used by patients coming from rural areas (32.3% of patients from rural areas). Alcohol was included in the overdose in 8.4%. Of the patients, 16.2% had a previous history of overdose. In this case series, psychiatric assessment suggested that 52% of the patients had a formal psychotic diagnosis, 21% had personality disorder and 27% had taken an overdose in response to stress. The most frequently documented precipitating factors were family problems and disputes (37%). Unusually, the seasonal distribution in these patients suggested a peak in summer (37.5% of presentations) with lower numbers in spring (30.2%), autumn (17.7%) and winter (14.6%). Of the patients, 23.7% presented in July. A total of 73.5% of patients was conscious, 16.4% was somnolent, 4.5% was in precoma and 5.6% was in coma (GCS <8). Patients who received antidotal therapy comprised 17.9%. Evidence of hepatic dysfunction was observed in 8.9% of patients and renal dysfunction in 3.6%. Extracorporeal techniques for drug removal (hemodialysis and hemoperfusion) were used in 2.2% of patients. Intensive care therapy was required in 11.4% of patients. The mean overall hospitalization time was 3.3 days. The mortality rate was 2.9%. CONCLUSIONS: This study shows that the epidemiology of self-harm by overdose in Greece is significantly different in terms of the seasonal presentation from other parts of Europe. The agents ingested and other features are similar to northern Europe. Psychiatric diagnoses are more common in our group than in those reported from northern Europe.

Autologous stem cell transplantation in progressive multiple sclerosis--an interim analysis of efficacy.

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.

Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): relation to disease status.

Various genetic abnormalities are often found in B-CLL, but their relative importance in the pathogenesis and evolution of the disease has not been adequately clarified. We studied the expression of bcl-2 protein and the possible simultaneous occurrence of bcl-2 overexpression, trisomy 12 and the Rb1 and p53 gene deletions in 38 patients with B-CLL by combining immunophenotyping and dual color interphase FISH. We also looked for correlation between the genetic abnormalities and clinical parameters such as stage, disease duration from diagnosis to the time of study and overall survival. High expression of the bcl-2 protein was found in 76.3% of the patients (29/38). Trisomy 12 was found in 37% of cases (14/38) and Rb1 monoallelic gene deletion in 42% (16/38). The percentage of cells with hemizygous Rb1 deletion ranged from 13 to 18%. Monoallelic deletion of p53 was found in 29% of cases (11/38). The number of cells with only one signal ranged from 28 to 98%. Patients in stage A had on average, less than one abnormality, while patients in stage C had 2.6 abnormalities. Patients appeared to accumulate genetic abnormalities with time. Bcl-2 overexpression was found early in the course of the disease. Trisomy 12 appeared later, at about the same time as Rb1 deletion, but was not associated with adverse prognosis. Monoallelic deletion of p53 gene appeared rather late in the course of the disease and was associated with advanced stage. Despite the fact that more deaths occurred in the group of patients with three or four abnormalities and the presence of p53 gene deletion, differences in survival were not statistically significant, probably due to the limited number of patients in each group. A larger group of patients studied in a prospective manner will better clarify these issues in the future.