Spontaneous gastroduodenal perforation in cancer patients receiving chemotherapy

BACKGROUND/AIMS: Spontaneous gastroduodenal perforation is a rare and lethal complication in cancer patients receiving chemotherapy. METHODOLOGY: Data of 9 patients with spontaneous gastroduodenal perforation occurring during chemotherapy were reviewed. RESULTS: All 9 patients were male with an average age of 54.4+/-2.5 years. The primary malignancies included 5 head and neck cancers, 2 esophageal cancers, 1 malignant lymphoma, and 1 hepatocellular carcinoma. Abdominal pain was the most common symptom. The average interval between the onset of symptoms and surgery was 2.9+/-0.7 days (range: 16 hours to 7 days). Perforation was located on the duodenum (6 patients) and on the lower part of the body of the stomach (3 patients). Simple closure of the perforation was performed on 8 patients, and subtotal gastrectomy on 1 patient. Culture of the ascitic fluid of 8 patients revealed E. coli, Klebsiella pneumoniae, streptococcus viridans, and enterococcus. Four patients (44.4%) had post-operative complications. The 30-day post-operative mortality was 44.4% (4/9). Three patients died of sepsis with multiple organ failure, and 1 died of hepatic failure. Age, anaemia, leukopenia, serum albumin levels, impaired renal or liver functions are not significant operative risk factors. Pre-operative shock is a significant factor in predicting operative mortality and complications. CONCLUSIONS: High index with suspicion of the disease with early treatment may improve survival of cancer patients with spontaneous gastroduodenal perforation.     

Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation

Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240 bp fragment comprising the pre-core region of HBV was amplified by polymerase chain reaction (PCR). Pre-core mutants of HBV were determined by direct sequencing of these PCR products and by sequencing of PCR clones. Eight of 17 patients were infected with pre-core wildtype HBV before OLT (group A). Seven of eight patients of group A were reinfected by pre-core wildtype HBV after OLT. In one of eight patients in addition to wildtype HBV a mutant strain (nt. 1899 G-->A) was detected. Nine of 17 patients were infected with pre-core mutant HBV before OLT (group B). Six of nine patients of group B were reinfected with the same mutant population; in one, an additional pre-core mutation emerged; two patients lost pre-core mutant HBV (nt. 1896 and 1899 G-->A). In one of the latter two, a pre-core start-codon mutant (nt. 1816 G-->T), not detectable before OLT, emerged, in the other a nt. 1897 G-->A stop-codon mutant persisted. Five patients of each group were followed-up for more than 24 (25 to 58) months on immunosuppressive therapy. In all five patients of group A, pre-core wildtype of HBV persisted during long-term follow up. Two of five patients of group B were infected stably with a stop-codon HBV-mutant nt. 1896. In three patients, the nt. 1896 stop-codon mutant disappeared during immunosuppressive therapy. However, in one of the latter three, an HBV stop-codon mutant nt. 1897 persisted. In conclusion, most patients who underwent OLT for HBV-related disease were reinfected with the same virus population that existed before OLT. In rare cases, new mutants emerged after OLT or preexisting mutants were lost. During long-term follow-up on immunosuppressive therapy, in the majority of patients pre-core mutants disappeared and wildtype HBV became the predominant virus strain.     

Immunology in clinical practice. VI. Current immunosuppressive drugs

Immunosuppressive drugs are agents capable of modulating at least one type of immune response in vivo at doses with tolerable side-effects. Classical immunosuppressive drugs include corticosteroids, azathioprine, cyclophosphamide, methotrexate and cyclosporine. In the past two years tacrolimus and mycophenolate mofetil were registered as immunosuppressive drugs. Tacrolimus interferes with the calcium-dependent signal transduction of T-lymphocytes. Mycophenolate mofetil is an inhibitor of purine synthesis by inhibition of the enzyme inosine monophosphate dehydrogenase. Both tacrolimus and mycophenolate mofetil have proven efficacy in both prevention and treatment of acute allograft rejection. The new drugs are stronger than the classical ones but do not cause more adverse reactions. The value in clinical medicine of some new, promising immunosuppressive drugs, i.e. sirolimus (rapamycin), mizoribine, brequinar and leflunomide remains to be proven.     

Intestinal perforation in temporal arteritis, associated with paroxysmal nocturnal hemoglobinuria

Patients with peripheral arterial occlusion may be treated with one of three distinct treatment strategies: observation and/or anticoagulation alone, operative intervention, or catheter-directed thrombolytic therapy. The severity of symptoms is the most important clinical parameter with which to formulate clinical strategies. Patients with non-lifestyle limiting claudication may be best managed without arteriographic investigation, managing symptoms conservatively with exercise, cessation of smoking, and occasionally the oral pharmacologic agent pentoxifylline. Patients with threatened limbs in the form of rest pain or tissue loss carry a high risk of limb loss without intervention. These patients should undergo arteriography with consideration of endovascular intervention for focal lesions and bypass grafting for more diffuse disease. Patients with more acute symptoms may be best treated with catheter-directed thrombolytic therapy, addressing unmasked lesions responsible for the occlusion with an operative or endovascular approach. In all cases, the appropriate therapy must be tailored to the clinical presentation, the anatomic distribution of disease, and the experience of the clinical team.     

Activity of various immunosuppressive drugs on tuberculin hypersensitivity reaction in chickens

Drug induced immunosuppression of chicken immune response was studied in F1 hybrids of the CB and IC inbred lines. In tuberculin reaction complete inhibition of wattle swelling was induced by the administration of methotrexate, colcemid (1 mg/KBW), and 6-mercaptopurine. The cellular infiltration was substantially reduced in these cases. Cyclophosphamide and colcemid (0.1 mg/KBW) reduced partially the wattle swelling but had no apparent effect on the cellular infiltration. Acetinomycin D did not affect in measurable degree the wattle swelling. The histologic picture was in this case the same as in the control animals. The same drug administration schedule had less pronounced effect on anti-HSA antibody production. No anti-HSA antibody was found after the 500 mg/animal doses of 6-mercaptopurine. Significant reduction of anti-HSA titres was found after 50 mg/animal doses of 6-mercaptopurine, colcemid (1 mg/KBW), 25 MG/KBW or cyclophosphamide and after the methotrexate treatment.     

Omeprazole 20 or 40 mg daily for healing gastroduodenal ulcers in patients receiving non-steroidal anti-inflammatory drugs

Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence. Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of 3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or sulfated alcian blue stains were routinely performed in each biopsy to screen for amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to 90 years (mean, 61 years) at initial presentation. The most common symptoms at presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and weight loss/decreased appetite (n = 7). Five patients had a concomitant malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1). Two patients had known hereditary forms of amyloidosis. Five patients had amyloid diagnosed on another organ biopsy (excluding peripheral nerve). Histologically, amyloid was deposited in the interstitium or perivascular region in 14 muscles and endomysial region in seven muscles. All cases were confirmed with Congo red staining (apple green birefringence) or by electron microscopic identification of fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight muscles showed small group atrophy, and seven showed myofiber type grouping. Scattered regenerating muscle fibers were seen in nine cases, degenerating myofibers in six, and foci of chronic endomysial and perivascular inflammation in two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve biopsy specimen was evaluated in seven patients; all seven contained amyloid, confirmed either by Congo red staining or electron microscopic examination. In two nerves, there was a mild loss of myelinated axons; four had a moderate loss, and one, severe loss. Six of seven nerves showed predominantly axonopathic changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle biopsy specimens was low (in this series, 0.004%); (2) only a minority of patients had multiple myeloma, and most presented with muscle weakness/fatigue or autonomic symptoms; (3) most of the muscles showed neurogenic features histologically; (4) all concomitant sural nerve biopsy specimens contained amyloid, and most showed a predominance of axonopathic changes.     

Severe gastrointestinal hemorrhage due to Mycobacterium avium complex in a patient receiving immunosuppressive therapy

Intense immunosuppressive therapy is used frequently for treatment of systemic vasculitides, collagenoses, rapidly progressive glomerulonephritis, and after organ transplantation. Numerous serious treatment-related side effects include localized or disseminated opportunistic infections, and require careful monitoring of immunosuppressed patients. Gastrointestinal infections with Mycobacterium avium complex (MAC) or other nontuberculous mycobacteria have been previously identified in HIV seropositive patients only. We now report the first case of an HIV seronegative patient who received immunosuppressive therapy for rapidly progressive glomerulonephritis. The patient presented with severe lower gastrointestinal bleeding and was diagnosed to have ulcerative colitis due to infection with MAC. The patient recovered promptly after administration of antimycobacterial therapy. MAC infection should be included in the differential diagnosis of gastrointestinal bleeding in all immunodeficient patients. The significance of repeated colonoscopy to obtain multiple biopsy specimens with histological examination for foam cells and specific staining for acid-fast organisms is emphasized.     

Intestinal permeability and inflammation in patients on NSAIDs

PURPOSE: The purpose of this study was to determine whether high frequency fatigue was present in the diaphragm after intense whole body endurance exercise. METHODS: We used bilateral phrenic nerve stimulation (BPNS) before and during recovery from whole body exercise to detect fatigue in the diaphragm. To detect high frequency fatigue we used paired stimuli at 10, 20, 50, 70, and 100 Hz frequency and determined the transdiaphragmatic pressure (Pdi) response to the second stimulation (T2). RESULTS: The subjects (N = 10) exercised at 93.3 +/- 2.3% of their VO2max for 9.9 +/- 0.5 min. The Pdi response to "twitch" and 10 Hz "tetanic" stimulation was decreased immediately after exercise versus pre-exercise values (-23.4 +/- 3.3%). The T2 amplitude was substantially reduced at all frequencies immediately after exercise (-28.0%), but by 30 min into recovery the T2 amplitude at 70 and 100 Hz was not different from pre-exercise values. In contrast, at 10 and 20 Hz the T2 response was still significantly reduced. CONCLUSIONS: We interpret these data to mean that high frequency fatigue as well as low frequency fatigue were present in the diaphragm after intense whole body endurance exercise.     

Surgery on patients receiving anticoagulants

Patients on anticoagulants may undergo surgery if the anticoagulants are carefully controlled and if contraindications are respected. Patients being treated for thromboembolism should have their clotting times maintained at close to two times normal levels if they are on heparin, or their prothrombin times similarly maintained if they are an oral anticoagulants.