Appendicolith as a cause of late complications after appendectomy - a case report and literature review.

INTRODUCTION: Acute appendicitis is one of the most common acute abdominal conditions. One of its complications is postoperative formation of abscesses in the peritoneal cavity or in the retroperitoneal space. Among other things, appendicoliths left in the peritoneal cavity are responsible for this process. Their release from the lumen occurs preoperatively and during the operation. An appendicolith, with the bacteria present on its surface, provides an environment that supports the onset of an infection. CASE REPORT: The authors present a less common case of a retroperitoneal abscess caused by an incarcerated appendicolith. Unusual is the long period between appendectomy and clinical manifestations of the abscess. The patient underwent surgical treatment with abscess evacuation and extraction of the appendicolith. The postoperative course was adequate; wound healing was supported by negative wound pressure therapy. CONCLUSION: During appendectomy, it is necessary to keep in mind the risk of releasing appendicoliths and their role in infectious complications. A conscientious revision of the peritoneal cavity is required, as well as a good surgical technique. If necessary, imaging methods can help to locate the appendicolith in the postoperative period.

Surgical treatment of hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) in Europe and throughout the world is currently increasing. This is caused by an increase in the number of patients with alcoholic liver damage, metabolic syndrome, and by increasing incidence of hepatitis B and C.From January 1, 2004 to December 31, 2013, resection or radiofrequency ablation of the liver was done in 360 patients with benign lesions or malignant tumors of the liver. In 28 patients HCC was diagnosed and histologically confirmed (7.8 %). Seven patients had HCC associated with liver cirrhosis (25 %), and 21 patients were without histologically confirmed cirrhosis (75 %). R0 resection was done in 18 (64 %) patients.Surgical complications occurred in 6 (21 %) patients and reoperation due to tumor relapse or progression was done eight times in 6 (21 %) patients. One-year and five-year patients' survivals were 64 % and 10 %, repectively, and did not statistically differ from the survival of the whole set of patients with tumor diseases in the given time period. In the future it will be possible to improve the long-term survival of patients with HCC by using screening methods for presymptomatic diagnosis of HCC, precise preoperative diagnosis and efforts for R0 resection (Tab. 1, Fig. 4, Ref. 11).

Treatment results of non-varicose bleeding from upper gastrointestinal tract.

UNLABELLED: Treatment results of non-varicose bleeding from upper gastrointestinal tract are changing by improved endoscopic methods and introduction of new drugs in treatment. OBJECTIVE: Objective of this work was to compare the results in treatment of patients with non-varicose bleeding from upper gastrointestinal tract in two different 5-years periods. MATERIAL: We hospitalised 229 patients with non-varicose bleeding from upper gastrointestinal tract at the Department of Surgery in Faculty Hospital of Martin in the period 1992-1996. (161 men and 68 women, average age 56.7, patients up to 60 were 42.4%). 203 patients were hospitalised in the years 2003-2008 (146 men and 57 women, average age 61.5, patients up to 60 were 54%). METHODS: We compared both groups by retrospective analysis and we evaluated differences by using statistical methods (nonparametric test of independence of the qualitative data). RESULTS: There was only minimal difference in primary conservative and endoscopic haemostasis in both groups. Relaps of bleeding was the same in both groups. Definitive conservative and endoscopic haemostasis was higher by 3.2% in the period 2003-2008 and number of urgent operations decreased by 5.1%. Differences in total mortality were minimal between both groups but postoperative mortality was higher by 5.9% in the years 2003-2008. CONCLUSION: Number of urgent operations decreased due to improved results in definitive conservative and endoscopic haemostasis in the treatment of non-varicose bleeding from upper gastroinestinal tract. There was no significant change in the relaps of bleeding. There were only minimal changes in total mortality between both groups, but postoperative mortality increased in the second period (Tab. 8, Ref. 35).

[Neuroendocrine tumours of the upper gastrointestinal tract, characteristics and comparison of localization diagnostics]. / Neuroendokrinné nádory horného tráviaceho traktu, charakteristika a porovnanie efektivity lokalizacnej diagnostiky.

In daily clinical practice it's important to think of neuroendocrine tumors, since their prevalence for the past 5 years exceeded even the common occurrences of stomach, esophageal and pancreatic cancers. Patients diagnosed early and accurately with NET, have a greater chance for complete cure. The diagnostic tools over the past century were significantly inefficient in diagnosing NET i.e. (40% of tumors were not localized after USG, CT, MRI, AG investigations). Until the past 2 decades that major turnover in diagnostic methods has been achieved. In particular, the introduction of the somatostatine receptor scintigrafy (SRS) and endoscopic ultrasonography (EUS) have increased sensitivity of localization diagnostics up to 90%. Our work is to test the success of the localization diagnostics in 22 patients with surgically and histologically confirmed NET ofthe pancreas and duodenum. These patients fulfilled jointly SRS, CT and/or MRI, but also classic USG and EUS. From our comparison, clearly endoscopic USG is the most efficient tool with 90% sensitivity.

[Intrathoracic goitre--undiagnosed--nevertheless operated]. / Intratorakální struma--nediagnostikovaná--prece odoperovaná.

A case review of a female patient, who was indicated for surgery for a goitre with minor bilateral retrosternal spread. The procedure included bilateral thyroidectomy during which the surgeon noticed unusual intrathoracic pathology in the left hemithorax, under the removed lobe. Postoperative chest x-ray and CT examinations revealed intrathoracic goitre, which was then removed during a following procedure. In the article, the authors discuss this uncommon pathology. Because of its uncommon location, the pathology was not detected on standard preoperative endocrinological examination. It was the follow up, postoperative examination, based on which the correct treatment was initiated.

Itinerant spin excitations near the hidden order transition in URu(2)Si(2).

By means of neutron scattering we show that the high temperature precursor to the hidden order state of the heavy fermion superconductor URu(2)Si(2) exhibits heavily damped incommensurate paramagnons whose strong energy dispersion is very similar to that of the long-lived longitudinal f spin excitations that appear below T(0). This suggests that there is a strongly hybridized character to the itinerant excitations observed previously above the hidden order transition. Here we present evidence that the itinerant excitations, like those in chromium, are due to Fermi surface nesting of hole and electron pockets; hence the hidden order phase probably originates from a Fermi surface instability. We identify wavevectors that span nested regions of a f-d hybridized band calculation and that match the neutron spin crossover from incommensurate to commensurate on approach to the hidden order phase.

Consideration of endoscopic retrograde cholangiopancreatography in cases of acute biliary pancreatitis.

AIM: The important question to be answered in all cases of ABP is whether or not a calculous biliary obstruction is still present. Answering this question conditions subsequent management, including the need for endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the relationship between persistent common bile duct stone (CBDS) and laboratory values, and dilation of bile duct in order to find possible significant associations in patients with acute biliary pancreatitis (ABP). METHODS: Retrospectively, statistical evaluation of a group of 76 patients with ABP who had received early ERCP. RESULTS: The prevalence of choledocholithiasis in patients > 70 years old was 54.2%, in patients < or = 70 years old it was 36.5%. Following cholecystectomy, CBDS was present in 81.8% of patients, p = 0.005. The probability of CBDS occurrence in patients > 70 years old with bile duct dilation was 81.3%; in the absence of bile duct dilation CBDS was not present, p < 0.001. The probability of CBDS occurrence in patients 70 years old with bile duct dilation was 57.7%, in the absence of bile duct dilation CBDS was present in 15.4%, p = 0.002. In patients with bile duct dilation predictive factors are as follows: bilirubin (Bi), after excluding patients with acute cholecystitis and cholangitis, p = 0.05; alanine aminotransferase (ALT) in patients 70 years old, p = 0.004; gamma-glutamyl transferase (GMT) in patients > 70 years old, p = 0.02. CONCLUSIONS: ERCP is indicated in patients with ABP if biliary obstruction is present and the presence of a ductal stone is suspected. From our results it is clear that the predictive parameter for choledocholithiasis is the dilation of the bile duct and previous cholecystectomy. In patients with bile duct dilation possible predictive factors are Bi, ALT, and GMT (Tab. 1, Fig. 8, Ref. 20).

DUHOCAMIS: a dual hollow cathode ion source for metal ion beams.

In this paper we describe a novel ion source named DUHOCAMIS for multiply charged metal ion beams. This ion source is derived from the hot cathode Penning ion gauge ion source (JINR, Dubna, 1957). A notable characteristic is the modified Penning geometry in the form of a hollow sputter electrode, coaxially positioned in a compact bottle-magnetic field along the central magnetic line of force. The interaction of the discharge geometry with the inhomogeneous but symmetrical magnetic field enables this device to be operated as hollow cathode discharge and Penning discharge as well. The main features of the ion source are the very high metal ion efficiency (up to 25%), good operational reproducibility, flexible and efficient operations for low charged as well as highly charged ions, compact setup, and easy maintenance. For light ions, e.g., up to titanium, well-collimated beams in the range of several tens of milliamperes of pulsed ion current (1 ms, 10/s) have been reliably performed in long time runs.

[Cystic feochromocytoma, mimicing a liver cyst. A case review]. / Cystický feochromocytóm, imitujúci cystu pecene.

Cystic feochromocytoma is a special subtype of supraadrenal tumors, with a specific clinical course, symptomatology, CT and MRI pictures and histological findings. The above factors frequently contribute to a wrong diagnosis and increased risk during its surgery. The authors present a case review of a patient with a cystic tumor of the right liver lobe. Its laparoscopic fenestration attempt resulted in hypertonic crisis with cardial decompensation and lung edema. Furthermore, attempts to embolize the tumor resulted in another hypertonic crisis, despite of the preoperative care as appropriate in feochromocytoma procedures. Only complete surgical removal of the tumor relieved the patient of the clinical symptoms. The authors discuss diagnostic and therapeutical problems of this specific and rare feochromocytoma subtype and suggest radical surgical management following a standard preoperative care as appropriate in all feochromocytoma procedures.

An alternative approach to carbon nanotube sample preparation for TEM investigation.

A two-stage replication technique (positive replica) is shown to be suitable for transmission electron microscopy (TEM) examination of carbon nanotubes (CNTs) and other one-dimensional nanostructures in their longitudinal direction. This method enables handling the fragile nanostructures, is fast and simple and allows to study the growth mechanism of nanofeatures, including the early stages of their growth. CNTs may also be examined when the growth layers are very thin, and even when only a few nanotubes are on a substrate. Replicas can be taken from various substrate shapes covered with nanostructures and from minute or specifically selected areas of the substrates. CNTs extracted by the replica are not disturbed, and their nanostructures are preserved. It is demonstrated that using positive replicas, HRTEM images from the nanosized carbon forms can also be obtained.

Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma.

BACKGROUND: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclophosphamide or doxorubicin or by the biologic agent interferon alpha. PURPOSE: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN alpha-2a) in patients with metastatic melanoma and renal cell carcinoma. METHODS: IL-2 (3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN alpha-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. RESULTS: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. CONCLUSIONS: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN alpha-2a as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen.

Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma.

BACKGROUND: The rising incidence of malignant melanoma and the lack of curative therapies for metastatic disease represent a therapeutic challenge. New agents effective in treating this disease are needed. PURPOSE: Because of the additive antitumor effects of interleukin 1 alpha (IL-1 alpha) and indomethacin in vivo, we conducted a phase II trial of this combination in patients with melanoma. We used the recommended dose determined from our phase I trial to ascertain the antitumor activity of the combination. METHODS: From August 1, 1990, through July 28, 1992, 49 patients entered the study. They were stratified into two groups based on the presence of visceral (n = 14) and nonvisceral (n = 35) metastases. The patients received 7 days of both IL-1 alpha (O.1 micrograms/kg per day by intravenous bolus) infusion) and indomethacin (50 mg orally every 8 hours). At least two cycles of therapy, repeated at 21-day intervals, were planned. Additional treatment was given to those patients who had stable or responding lesions. A chi-squared test for homogeneity of proportions was used to compare groups on several measures. All P values resulted from two-sided tests. RESULTS: Fever, chills, and hypotension were among the most common side effects. None of the 14 patients with visceral metastases responded to the treatment. Of the 35 patients with non-visceral metastases, three showed a partial response for 6 months each and one showed a complete response for more than 34 months; the response rate was 11% (95% confidence interval [CI] = 5%-26%). All responding patients required phenylephrine for treatment of IL-1 alpha-induced hypotension, whereas six (19%) of 31 of the nonresponding patients with nonvisceral metastases required phenylephrine (P = .0008). The response rate in women was higher; three of 10 women (30%; 95% CI = 11%-60%) responded, whereas one of 25 men (4%; 95% CI = 0%-20%) responded (P = .029). All three women were positive for human leukocyte antigen (HLA) B7 expression (P = .011). CONCLUSIONS: The combination of IL-1 alpha and indomethacin has minimal antitumor activity in melanoma patients. All responses were confined to patients with nonvisceral metastases. IL-1 alpha-induced hypotension, gender, and HLA B7 expression were positively associated with response. IMPLICATIONS: Administration of higher doses of IL-1 alpha alone has been shown to produce hypotension in a large proportion of patients but can be given safely with phenylephrine support. Because of the association of hypotension with antitumor activity, treatment with higher IL-1 alpha doses alone may be a strategy for attaining better response rates.

Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: changes during treatment.

Interstitial pressure (IP) is a physiological variable that may have its greatest influence on the transport of high-molecular-weight therapeutic agents. IP in tumor nodules was measured in patients with metastatic melanoma or non-Hodgkin's lymphoma to determine the influence of this physiological variable on treatment outcome. The wick-in-needle technique was used to measure IP at time points before and after treatment with a variety of immunotherapy and chemotherapy regimens. Selected patients had IP measurements during chemotherapy or immunotherapy infusions. Ultrasound or computed tomography was used to evaluate the size of the studied lesions and their relationship to normal structures. The mean baseline IP in melanoma nodules (n = 22) and lymphoma nodules (n = 7) was 29.8 and 4.7 mm Hg, respectively (P = 0.013 for the difference between tumor types). In a subset of melanoma nodules for which IP had been measured before and after treatment, the IP increased significantly over time for nonresponding melanoma lesions from a baseline of 24.4 to 53.9 mm Hg after treatment (P = 0.005) and decreased in melanoma lesions that responded to treatment where the mean baseline and post-treatment IPs were 12.2 and 0 mm Hg, respectively (P = 0.001 for the difference in IP profiles between responding and nonresponding lesions). Six of seven lymphoma nodules responded completely to chemotherapy or radiation. The single nodule that did not respond had a baseline IP of 1 mm Hg that increased to 30 mm Hg after treatment. Tumor IP differs significantly between melanoma and non-Hodgkin's lymphoma. The changes in IP over time differ significantly between responding and nonresponding melanoma lesions. IP that increases during treatment appears to be associated with tumor progression in these tumor types.

CNS involvement in primary mediastinal large B-cell lymphoma.

PURPOSE: The risk of CNS involvement by non-Hodgkin's Lymphoma (NHL) has been associated with bone marrow and/or testicular involvement; however, it was recently reported that the number of extranodal sites is a more reliable predictor of CNS disease. Because primary mediastinal thymic large B-cell lymphoma (PMLCL) has a high propensity for involving extranodal sites, we investigated the frequency and pattern of CNS involvement in PMLCL. PATIENTS AND METHODS: The medical records of 219 patients with aggressive NHL, consecutively entered onto protocols at the National Cancer Institute between 1987 and 1998, were retrospectively reviewed. RESULTS: Twenty-three patients (11%) had clinical and pathologic features of PMLCL. These patients were young (median age, 29 years), female (61%), and presented with massive mediastinal adenopathy (70%). Extranodal disease occurred at presentation in 70% and at relapse in 93% of patients and involved contiguous intrathoracic structures and/or distant sites, including the lungs, kidneys, liver, adrenals, ovaries, pancreas, and bone. Six patients (26%) developed CNS involvement, two (9%) at presentation and four (27%) at relapse. All had extranodal disease, but only one had bone marrow involvement. Parenchymal and leptomeningeal CNS disease occurred in four and three patients, respectively. CONCLUSION: CNS involvement in PMLCL is associated with extranodal involvement other than bone marrow and may reflect the unique biology of this disease. The propensity to involve the CNS parenchyma raises the concern that intrathecal prophylaxis may not be effective and suggests that CNS imaging should be considered in patients with extranodal disease.

High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer.

PURPOSE: We investigated whether carboplatin myelosuppression could be favorably modulated by the administration of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in patients with advanced-stage ovarian cancer. PATIENTS AND METHODS: Thirty-four patients with advanced-stage recurrent ovarian cancer were treated with high-dose carboplatin (800 mg/m2 per 35-day cycle) and rGM-CSF. rGM-CSF was administered as a daily subcutaneous injection starting 72 hours after the carboplatin dose and continuing until 7 days beyond the WBC nadir. rGM-CSF was administered in a phase I fashion. Seven patients were treated at an rGM-CSF dose of 3 micrograms/kg, 11 at 5 micrograms/kg, 10 at 10 micrograms/kg, and six at 20 micrograms/kg. RESULTS: rGM-CSF-related toxicities that were not dose-related included nonneutropenic fever, rib pain, acute hypersensitivity reaction, and pericarditis. At the rGM-CSF dose of 20 micrograms/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting toxicity. Patient tolerance of the 3-micrograms/kg and 5-micrograms/kg doses was good, but tolerance was limited for the 10-micrograms/kg dose. Febrile neutropenia was seen in four of seven patients at 3 micrograms/kg, two of 11 at 5 micrograms/kg, two of 10 at 10 micrograms/kg, and one of six at 20 micrograms/kg. Cumulative carboplatin myelotoxicity was blunted only in respect to WBC count, and not for platelets or RBCs. Gastrointestinal bleeding was seen in seven patients. The administered dose-intensity of carboplatin averaged 134 mg/m2/wk for the cohort, or 670 mg/m2 per 35-day cycle. There were two clinical complete responses and eleven partial responses, for a response rate of 38%. CONCLUSION: rGM-CSF appears to be effective and tolerable at 5 micrograms/kg/d administered subcutaneously, if given with carboplatin doses up to approximately 600 mg/m2 over 35 days. The use of rGM-CSF with high-dose carboplatin is associated with a substantial response rate in poor-prognosis ovarian cancer patients.

Dose-related immunologic effects of levamisole in patients with cancer.

PURPOSE: This phase I study was conducted to determine the maximum-tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-gamma). PATIENTS AND METHODS: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN-gamma 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. RESULTS: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-gamma. Dose-related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of > or = 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-gamma and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-gamma alone. CONCLUSION: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.

The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies.

PURPOSE: A phase I trial was undertaken because interleukin-1 alpha (IL-1 alpha) possesses antiproliferative, immunostimulatory, antiinfection, myeloprotective, and myelorestorative properties that could be beneficial in cancer treatment. PATIENTS AND METHODS: In this phase I trial, IL-1 alpha was administered intravenously (IV) during a 15-minute period daily for 7 days to patients with advanced solid malignancies. RESULTS: The maximum-tolerated dose (MTD) of IL-1 alpha alone was 0.3 microgram/kg. A second group of patients received indomethacin plus IL-1 alpha based on preclinical studies, which indicated that indomethacin could abrogate IL-1 alpha-induced hypotension; however, the MTD of IL-1 alpha plus indomethacin was 0.1 microgram/kg lower than IL-1 alpha alone. Fever, chills, headache, nausea, vomiting, and myalgia were common but were not dose-limiting. Hypotension resulted from a marked decrease in systemic vascular resistance and required pressors at 0.3 and 1.0 micrograms/kg IL-1 alpha. Dose-limiting toxicities included hypotension, myocardial infarction, confusion, severe abdominal pain, and renal insufficiency. IL-1 alpha treatment caused a significant, dose-related increase in the total WBC count (mainly segmented neutrophils and neutrophilic bands). Bone marrow cellularity increased because of enhanced numbers of relatively mature myeloid cells and megakaryocytes. Platelet counts decreased during therapy but were significantly elevated above baseline values 1 to 2 weeks posttreatment; this may have been an effect of IL-6 that was shown to be induced by IL-1 alpha treatment. Significant increases in triglycerides, cortisol, C-reactive protein, thyroid-stimulating hormone and decreases in cholesterol, testosterone, and protein-C were observed with treatment. CONCLUSION: We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur.

Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer.

PURPOSE: We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS: The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION: CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.

Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer.

PURPOSE: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFN alpha-2a) that can be administered chronically on an outpatient basis. PATIENTS AND METHODS: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m2) Monday through Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m2) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. RESULTS: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. CONCLUSION: IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.

The significance of clinical markers in the prediction of hemodynamic and cardiac complications of capnoperitoneum in patients at risk.

OBJECTIVES: The aim of this prospective study was to find out the predictive value of concomitant diseases of cardiovascular system (CVS), lungs and kidneys as well as metabolic diseases to be able to anticipate the potential origin of hemodynamic and cardiopulmonary complications as a result of insufflated CO2 peritoneum. METHODS: The study investigated eleven patients at the anaesthetic risk of ASA III-IV and cardiac risk of NYHA II-III in whom elective laparoscopic surgical intervention had been indicated. RESULTS: We have found out that the significance of the increase in biologic ANP markers, catecholamines and PRA was not sufficient to signal the deepening of cardiac dysfunction, latent cardiac failure or hemodynamic disorder (p > 0.01). The courses of regression lines have shown the dependence on the increased IAP (intra-abdominal pressure) of capnoperitoneum in PRA and adrenaline. The reactions of biologic markers correlated with reactions of clinical hemodynamic markers of BP and HR. We have proved that the increased level of IAP causes a significant increase in CVP (p < 0.01) being one of the factors determining the preload of right ventricle (RV) and in coincidence with intact transpulmonary circulation also the optimal function of left ventricle (LV). CONCLUSION: Our investigation of peroperative clinical and biologic markers of hemodynamics and neuroendocrine response to operative stress and development of CO2 peritoneum has proved that the course of laparoscopic operations in patients in the risk group of ASA III-IV and NYHA III does not necessarily have to be deteriorated by complications. It can be assumed that increased values of biologic markers regulate the neurohumoral response in the physiologic range and do not predict a severe CVS dysfunction within its course. (Tab. 2, Fig. 3, Ref. 22.)