Decreasing medication errors in four intensive care units of a tertiary care teaching hospital in India using a sensitization programme.

Background: Medication errors have an adverse impact on the healthcare system by increasing patient morbidity and mortality. They are preventable, and educational or technology-based interventions are needed to reduce their prevalence and improve medication safety. We aimed to study the impact of a sensitization programme and a blame-free reporting tool for doctors and nurses on the prevalence and reporting of medication errors in the intensive care units (ICUs) of a tertiary care teaching hospital. Methods: This prospective interventional study was conducted in the ICUs of cardiology, medicine, paediatrics and neonatology. Baseline medication errors were detected by prescription order review and direct observation of administration of medication for 30 days. A sensitization programme was conducted for doctors and nurses in these ICUs, the results were discussed, and a blame-free medication error reporting tool was introduced. Medication charts were modified to remove the transcription process in the cardiology and paediatrics ICUs. The follow-up study was conducted for 30 days in each ICU to monitor the impact of the sensitization programme. Results: The prevalence of medication errors was found to be 334.1/1000 patient observation days. Prescription errors were the most common types of errors at 129.1/1000 patient observation days. The interventions significantly reduced the error rate in all four ICUs. The overall number of prescriptions with errors was reduced from 9.1% (177/1944) to 3.5% (48/1373) and no medication error was reported using the tool. Conclusion: The sensitization programme on medication errors for doctors and nurses may be effective in improving medication safety. The impact was more pronounced in prescription errors. Reporting of medication errors did not improve in this study despite the introduction of a blame-free reporting tool.

Candesartan cilexetil ameliorates NOSTRIN-NO dependent portal hypertension in cirrhosis and ACLF.

In decompensated cirrhosis, the severity of portal hypertension (PHT) is associated with increased hepatic endothelial nitric oxide synthase (eNOS) trafficking inducer (Nostrin), but the mechanism remains unclear. AIM: To investigate: (1) Whether in cirrhosis-PHT models, ± superimposed inflammation to mimic acute-on-chronic liver failure (ACLF) modulates hepatic nitric oxide synthase trafficking inducer (NOSTRIN) expression, nitric oxide (NO) synthesis, and/or endothelial dysfunction (ED); and (2) Whether the "angiotensin II type 1 receptor blocker" candesartan cilexetil (CC) affects this pathway. CD-1 mice received intraperitoneal carbon tetrachloride injections (CCl4 15% v/v in corn oil, 0.5 mL/kg) twice weekly for 12 wk to induce cirrhosis. After 12 wk, mice were randomized to receive 2-wk oral administration of CC (8 mg/kg) ± LPS. At sacrifice, plasma (biochemical indicators, cytokines, and angiotensin II) and liver tissues (histopathology, Sirius-red stains, and molecular studies) were analysed. Moreover, Nostrin gene knockdown was tested in human umbilical vein endothelial cells (HUVECs). When compared to naïve animals, CCl4-treated animals showed markedly elevated hepatic Nostrin expression (P < 0.0001), while hepatic peNOS expression (measure of eNOS activity) was significantly reduced (P < 0.05). LPS challenge further increased Nostrin and reduced peNOS expression (P < 0.05 for both) in cirrhotic animals. Portal pressure and subsequent hepatic vascular resistance were also increased in all cirrhotic animals following LPS challenge. In CCl4 ± LPS-treated animals, CC treatment significantly reduced Nostrin (P < 0.05) and increased hepatic cGMP (P < 0.01). NOSIP, caveolin-1, NFκB, and iNOS protein expression were significantly increased in CCl4-treated animals (P < 0.05 for all). CC treatment non-significantly lowered NOSIP and caveolin-1 expression while iNOS and NFκB expression was significantly reduced in CCl4 + LPS-treated animals (P < 0.05 for both). Furthermore, Nostrin knockdown significantly improved peNOS expression and associated NO synthesis and reduced inflammation in HUVECs. This study is the first to indicate a potential mechanistic role for the Nostrin-eNOS-NO pathway in cirrhosis and ACLF development. Moreover, this pathway provides a potential therapeutic target given the ameliorative response to Candesartan treatment.

Investigations of an organic-inorganic nanotheranostic hybrid for pancreatic cancer therapy using cancer-in-a-dish andin vivomodels.

The incidence of highly aggressive pancreatic cancer is increasing across the globe and is projected to increase to 18.6% by 2050. The mortality rate for this form of cancer is very high and the 5 y relative survival rate is only about 9%-10%. The 3D pancreatic cancer microenvironment exerts a major influence on the poor survival rate. A key factor is the prevention of the penetration of the chemotherapeutic drugs in the three-dimensional (3D) microenvironment leading to the development of chemoresistance which is a major contributor to the survival rates. Hence,in vitrostudies using 3D cultures represent a better approach to understand the effect of therapeutic formulations on the cancer cells when compared to conventional 2D cultures. In the present study, we have explored three different conditions for the development of a 3D pancreatic tumour spheroid model from MiaPaCa-2 and PanC1 cells cultured for 10 days using Matrigel matrix. This optimized spheroid model was employed to evaluate a multi-functional nanotheranostic system fabricated using chitosan nanoparticles co-encapsulated with the chemotherapeutic agent gemcitabine and gold-capped iron oxide nanoparticles for multimodal imaging. The effect of the single and multiple-dose regimens of the theranostic system on the viability of 3D spheroids formed from the two pancreatic cancer cell lines was studied. It was observed that the 3D tumour spheroids cultured for 10 days exhibited resistance towards free gemcitabine drug, unlike the 2D culture. The administration of the multifunctional nanotheranostic system on alternate days effectively reduced the cancer cell viability after five doses to about 20% when compared with other groups. The repeated doses of the nanotheranostic system were found to be more effective than the single dose. Cell line-based differences in internalization of the carrier was also reflected in their response to the nanocarrier with PanC1 showing better sensitivity to the treatment.In vivostudies revealed that the combination of gemcitabine and magnetic field induced hypothermia produced superior regression in cancer when compared with the chemotherapeutic agent alone by a combination of activating the pro-apoptotic pathway and heat-induced necrosis. Our results reveal that this multi-functional system holds promise to overcome the current challenges to treat pancreatic cancers.

Development and evaluation of a multi-functional organic-inorganic nanotheranostic hybrid for pancreatic cancer therapy.

Pancreatic cancer is a highly invasive disease with low survival rates. The high death rates associated with pancreatic cancer are due to multiple factors including late stage diagnosis, multi-drug resistance, invasive nature and restricted access of the therapeutic moiety to the cancer cells due to the stroma. Smart multifunctional nanocarriers that deliver the therapeutic agent in to the cancer tissue as well as enable imaging of the tissue represent an emerging paradigm in cancer therapy. Accurate and reliable detection of cancerous lesions in pancreas is essential for designing appropriate therapeutic strategy to annihilate the highly aggressive pancreatic cancer. A combination of imaging modalities can enhance the reliability of cancer detection. In this context, we report here a hybrid iron oxide-gold nanoparticle with dual contrast enhancing ability for both magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) that is co-encapsulated with the nucleotide analogue gemcitabine in a chitosan matrix. The theranostic system displayed enhanced cytotoxicity against PanC-1 pancreatic cancer cells when compared to normal cells over 48 h due to differences in cell internalization. The iron oxide-gold hybrid enabled visualization of the theranostic nanoparticle by MRI as well as micro-CT. Further, the magnetocaloric effect of the iron oxide enabled faster release of the chemotherapeutic agent as well as augmented the cytotoxicity by inducing hyperthermia. This system holds promise for further exploration as an integrated diagnostic and therapeutic platform for pancreatic cancer.

Dataset for compression ignition engine fuelled with corn oil methyl ester biodiesel.

The present data study deals with the experimental analysis of performance, emission and combustion characteristics of CI engine fuelled with corn oil methyl ester biodiesel blend as alternative fuel. A two-step trans esterification process is used to produce the biodiesel. Furthermore, a characteristics study was carried out on the extracted corn oil methyl ester biodiesel blends over conventional fuel. Three different fuel blends namely B10, B20 and B30 were chosen and the performance, emission and combustion characteristics of these are compared to that of conventional diesel fuel. Eddy current dynamometer is used load the engine from no load to maximum load condition. Using AVL DiGAS 444 N gas analyser and AVL 346 smoke meter the emissions and smoke opacity of the fuel blends and diesel were measured respectively. The experimental performance, emission and combustion data's were presented.

Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells.

Cancer thermotherapy and radiofrequency ablation (RFA) have been adopted as modalities for treating various kinds of cancer. We have previously demonstrated that bone morphogenetic protein-4 (BMP-4) is up-regulated in colonic adenocarcinoma. Here, we investigated whether an increase of BMP-4 expression changes cellular response to heat treatment in human colon cancer HCT116 cells. BMP-4 overexpressing HCT116 cells generated by stable transfection showed a significantly increased survival rate and a decreased apoptotic rate in comparison to empty vector controls after heat treatment at 45 degrees C for 20min. The expression levels and pattern of HSP90, HSP70, and HSP27 after heat treatment were similar between these two cell lines. There was no difference in expression levels of Bcl-2 and Bax in these two cell lines and their expression remained unchanged after heat treatment. Both activities of the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were stimulated by heat in these cells. Comparatively, BMP-4 overexpressing cells had an intense and prolonged ERK activation, while a less intense and short JNK activation. Correspondingly, treatment of BMP-4 overexpressing cells with noggin, a BMP-4 antagonist, resulted in a reduction of heat-activated ERK but an increase of heat-activated JNK and significantly increased heat-induced apoptotic rate. These results indicate that BMP-4 can protect colon cancer cells from heat-induced apoptosis through enhancing the activation of ERK as well as inhibiting the activation of JNK.

Are Police Personnel in Puducherry Healthy? Findings from "Partners in Prevention" Programme in Puducherry, India.

BACKGROUND: Prevalence of cardiovascular diseases are reported to be high in police force, which constitute a special occupational group. "Partners in Prevention" was a special surveillance activity carried out among the personnel of the Department of Police, Government of Puducherry by JIPMER, Puducherry. The present study reports the prevalence of metabolic syndrome and other cardiovascular risk factors in this group. MATERIALS AND METHODS: The design was cross-sectional analytical study covering 1618 policemen during 2013-15. A pre-tested questionnaire was used for collecting data. Anthropometric and biochemical measurements were carried out using standard techniques. Metabolic syndrome was diagnosed using the International Diabetes Federation (IDF) consensus worldwide definition. Statistical analysis was performed using the IBM- SPSS 21 software. RESULTS: The mean (SD) age of the participants was 45.7 (10.1) years. Majority (90%) of the participants were males and were in the age group of 30-59 years. Metabolic syndrome was observed in two-fifth (42%) of the study population. We found the prevalence as: hypertension (45.2%), abnormal HDL levels (62.3%), diabetes (34.7.1%), and high body mass index of >=25 kg/m2 (60.5%). CONCLUSION: Our study identified that police personnel were having high CVDs and risk factors. It calls for an urgent need to initiate screening and secondary prevention programmes.

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.

Experimental and clinical observations on hepatic cryosurgery for colorectal metastases.

Cryosurgery, using liquid nitrogen at -196 degrees C, was explored for treating colorectal liver metastases in an experimental study of rat colon cancer and in a clinical investigation of patients with unresectable liver tumors. The viability of rat colon cancer isografts showed that while two or three freeze-thaw cycles were 100% effective in controlling established isografts and preventing isograft take, one freeze-thaw cycle was suboptimal. In these animals cryosurgery was as effective as surgical resection in controlling established experimental liver metastases. Cryosurgery by operative liver exposure and intraoperative ultrasound monitoring were used to treat liver metastases from colorectal cancer in 24 patients. At a median follow-up of 2 years (range, 5 months to 5 years), seven patients (29%) are disease free, eight (33.5%) are alive with recurrent tumors, and nine (37.5%) have died. The patterns of failure were: remaining liver and extrahepatic sites, ten patients (59%); remaining liver only, six patients (35%); and extrahepatic only, one patient (6%). These data demonstrate that cryosurgery is a useful modality for treating unresectable primary and metastatic liver cancers. Addition of systemic adjuvant therapy may improve the tertiary failure following the control of liver metastases.

Expression of a Mr 32,000 laminin-binding protein messenger RNA in human colon carcinoma correlates with disease progression.

Cell surface receptors for laminin may play an important role in tumor migration and metastasis. To evaluate laminin receptor/laminin-binding protein expression in human colon carcinoma, surgical specimens of primary colon cancers and liver metastases were examined by blot hybridization of total RNA with a complementary DNA clone which encodes a Mr 32,000 human laminin-binding protein. The mRNA level of the laminin-binding protein was higher in primary colon carcinoma than in adjacent normal colonic epithelium in 20 of 21 cases. In all 6 cases of colon cancer liver metastases, the laminin-binding protein mRNA level was more than 3-fold greater in tumor than in adjacent normal liver tissue. The tumor/normal ratio of this laminin-binding protein mRNA expression in primary colon cancer has significant correlation with Dukes' classification (P less than 0.001). Our results suggest that mRNA expression of the laminin-binding protein may be a marker of human colorectal cancer progression and biological aggressiveness.

Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene.

One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma.

Clinical evaluation of a side entry access port: a novel dual-lumen venous access device.

The initial clinical experience with a low-profile side entry access (SEA) dual-lumen implantable venous access port for cancer chemotherapy administration is summarized in this report. The catheter material is polyurethane. The overall experience in 35 patients in this study was a total of 6,224 patient days, with a mean of 178 days per patient. A variety of chemotherapeutic agents, biologic response modifiers, and antibiotics were administered. In 26% of the patients, the device chambers were in simultaneous use during the treatment period. A 6% incidence of clinical subclavian vein thrombosis was noted. There was no infectious complications. Inconsistencies in blood withdrawal and temporary catheter dysfunction were comparable to other access ports in clinical use. The novel design of this side entry port and the catheter material of low thrombogenicity make this device a good option in patients requiring a low-profile system and dual access. Nursing staff should be made aware of the side entry design and that in-service training for accessing the septum is required in centers where such devices are not routinely used.

A new peripherally implanted subcutaneous permanent central venous access device for patients requiring chemotherapy.

PURPOSE: A peripherally implanted central venous access device (P.A.S. Port; Pharmacia Deltec Inc, St Paul, MN) was evaluated for ease of insertion, functionality, acceptance, and complications in patients who required long-term venous access. A hand-held tracking system (Cath-Finder; Pharmacia Deltec Inc) used to determine catheter tip location was also evaluated. PATIENTS AND METHODS: A P.A.S. Port was placed in 47 patients who required long-term intravenous access. The median follow-up duration has been 32 weeks (range, 2 to 112). Total usage has been 2,028 catheter-weeks. The Cath-Finder was used to determine catheter tip location during insertion. Nursing staff and patient satisfaction were polled and functionality and complications were recorded. RESULTS: The device was found to be simple to insert, the procedure well tolerated, and, with one exception, the Cath-Finder accurately predicted catheter tip location. There was a 6.4% incidence of transient phlebitis and a 6.4% incidence of symptomatic axillary or subclavian vein thrombosis. There were no infectious complications. Access was simple in all but two obese patients. The device functioned well in all patients, except three in whom blood aspiration was difficult and two in whom fluid administration was slow. The device was well tolerated by all patients and nursing staff satisfaction was high. CONCLUSION: This device provides a highly acceptable, additional method of implantable, permanent central venous access for chemotherapy patients with a low complication rate. The successful use of the Cath-Finder and minor extent of the procedure may allow this device to be inserted in a clinic procedure room without sedation and fluoroscopy.

Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors.

PURPOSE: This prospective, nonrandomized trial evaluated a percutaneous isolated chemotherapy perfusion approach for treating advanced primary and metastatic liver tumors. Chemotherapy was administered via hepatic artery catheter and hepatic venous blood isolated by a novel percutaneous double-balloon inferior vena cava (IVC) catheter was passed through a detoxification/filtration cartridge in a venovenous bypass circuit. PATIENTS AND METHODS: Among 23 patients enrolled onto the study, 58 procedures were performed on 21 patients. Twelve patients received dose escalations of fluorouracil (5-FU) (1,000 mg/m2 to 5,000 mg/m2), and nine received dose escalations of doxorubicin (50 mg/m2 to 120 mg/m2). Pharmacokinetic studies included drug accumulation in the liver, extraction by detoxification filters, systemic exposure, and alterations of half-life. Each patient received two treatments at 3-week intervals. Those showing stabilization or response received additional treatments. RESULTS: There was a direct relationship between dose and peak concentration of drug entering the hepatic veins. The system functioned efficiently throughout the dose range, with extraction efficiencies ranging from 64% to 91% (P < .001). The hepatic vein drug levels showed a sixfold increase in 5-FU with dose escalation from 1,000 to 5,000 mg/m2, and a twofold increase in dox with dose escalation from 50 to 120 mg/m2 (P < .001, filter-mediated drug extraction). The treatments were accomplished with only an overnight hospital stay and no mortality. The common procedure-related toxicity was transient hypotension (grade I to II), due to catecholamine depletion by the filter. Dose-limiting toxicity (leukopenia) was observed in patients receiving 5-FU at a dose of 5,000 mg/m2 and doxorubicin at a dose of 120 mg/m2. Significant tumor response (> 95% reduction) was obtained in two patients receiving doxorubicin at 90 mg/m2 and 120 mg/m2. CONCLUSION: The use of a double-balloon catheter to isolate and detoxify hepatic venous blood during intraarterial therapy is technically feasible, safe, and allows administration of large doses of intrahepatic chemotherapy at short intervals. This approach should allow new dose-intensification strategies to increase tumor responses in primary and metastatic liver tumors.

Prospective comparison of preoperative imaging and intraoperative ultrasonography in the detection of liver tumors.

A prospective evaluation of the accuracy of preoperative computed tomography (CT), ultrasonography (US), and angiography was performed in 54 patients undergoing resection of hepatic neoplasms. The results were compared with surgical findings and intraoperative ultrasonography (IOUS). A total of 167 lesions was seen by means of IOUS, of which preoperative US enabled detection of 127 (76%). In 48 patients CT allowed detection of 91 of 150 lesions (61%), and in 35 patients angiography showed 56 of 107 lesions (52%). When the detection rate is analyzed according to hepatic segment, the greater overall accuracy of preoperative US may be attributed to a markedly better detection rate in lateral segment of the left lobe of the liver. Lesion size also represented a factor, with preoperative US allowing detection of a greater number of small (less than 2 cm) lesions compared with CT. In patients studied with both CT and US, the combined lesion-detection rate increased to 81% in the right lobe and 76% in the left lobe. Because of this we recommend that preoperative assessment include both CT and US evaluation of the liver. IOUS showed 25% to 35% additional lesions compared with preoperative US and CT. More importantly, 40% of the lesions demonstrated by IOUS were neither visible nor palpable at surgery. We recommend that IOUS be considered in all patients in whom resection of hepatic neoplasm is planned.

Ten-year follow-up of breast carcinoma in situ in Connecticut.

Statistics from the Connecticut Tumor Registry from 1979 to 1988 were examined, and individual medical records from 1979 to 1983 were also reviewed. Three hundred nineteen medical records were available for review, documenting 220 cases of ductal carcinoma in situ and 102 cases of lobular carcinoma in situ. In 1979, there were 33 new cases of ductal carcinoma in situ reported to the Connecticut Tumor Registry, representing 1.8% of all breast cancers. There has been a yearly increase in ductal carcinoma in situ, with 200 new cases, or 7.4% of all breast cancers, reported in 1988. Forty-eight (22%) of 217 patients with ductal carcinoma in situ had bilateral breast involvement with ductal carcinoma in situ or an invasive breast cancer. Ten (83%) of 12 mastectomy specimens from patients with ductal carcinoma in situ who presented with nipple discharge demonstrated residual tumor, suggesting a more diffuse involvement. Two of the three reported recurrences involved nipple discharge. Thirty-seven (16.8%) of the 220 patients with ductal carcinoma in situ and six (5.9%) of the 102 patients with lobular carcinoma in situ were diagnosed as having another unrelated cancer. Ongoing clinical trials will direct optimum therapy for patients increasingly diagnosed as having ductal carcinoma in situ.

Splenectomy. The treatment of choice for human immunodeficiency virus-related immune thrombocytopenia?

Immune thrombocytopenia is a well-recognized part of the clinical spectrum of infection with the human immunodeficiency virus. From November 1985 to February 1988, 15 patients who were human immunodeficiency virus-positive underwent splenectomy for refractory immune thrombocytopenia. Eight patients had thrombocytopenia only, and 7 others were pancytopenic prior to splenectomy. Three of the 15 patients fulfilled criteria for acquired immunodeficiency syndrome before splenectomy, and acquired immunodeficiency syndrome developed in 5 patients during the follow-up period. The median duration of thrombocytopenia prior to surgical therapy was 6 months. A bone marrow biopsy specimen showed hypercellularity with increased megakaryocytes. All patients had a therapeutic response to splenectomy. Long-term remission from thrombocytopenia/pancytopenia was achieved in 14 of the 15 patients during a follow-up period of 2 to 21 months. Splenectomy can be accomplished with an acceptable morbidity. Pneumonia developed postoperatively in 2 patients, but they did not manifest the characteristic picture of overwhelming postsplenectomy sepsis. They had received vaccinations against encapsulated organisms preoperatively. We conclude that splenectomy provides a durable and lasting response for HIV-related thrombocytopenia. Vaccination for Streptococcus pneumonia and Haemophilus influenzae should be given prior to splenectomy although its efficacy is not clear in this group.

Surgical resection for isolated cardiac metastases.

We performed what we believe to be the second successful resection of metastatic liposarcoma to the heart using cardiopulmonary bypass. Analysis of ten previous resections of cardiac metastases from a variety of tumors from distant primary sites revealed survivals from four months to two years. When patients can tolerate a major operative procedure, resection of solitary cardiac metastases can be successful if the primary tumor is well controlled. Patients with sarcomas and with long disease-free intervals should strongly be considered for aggressive surgical therapy. Computed tomographic scans of the chest were useful in the diagnosis and accurate delineation of the extent of tumor.

A 5-year study of cryosurgery in the treatment of liver tumors.

This report summarizes our 5-year experience with cryosurgery for in situ ablation of liver tumors. The liver was exposed with laparotomy, and the tumors were subjected to two freeze-thaw cycles using liquid nitrogen delivered by insulated probes; cryoablation was monitored with intraoperative ultrasonography. Tumor markers and computed tomography evaluated tumor response during long-term follow-up. From 1985 to 1990, 32 patients (19 men and 13 women) were entered into this study. The histologic characteristics of the tumors were as follows: colorectal, 24 patients; hepatoma, three patients; neuroendocrine, two patients; and others, three patients. After a follow-up period of 5 to 60 months (median follow-up, 24 months), nine patients (28%) remained disease free, 11 patients (34%) were alive with disease, and 12 patients (38%) died. The patterns of failure included liver and extrahepatic disease in 54% of cases, liver disease only in 32% of cases, and extrahepatic disease only in 14% of cases. In patients with "liver only" failure, recurrence at the treatment site occurred in three patients (9%). This study establishes the long-term effectiveness of cryosurgery in the treatment of primary and metastatic liver tumors.

Experimental liver metastasis. Implications of clonal proclivity and organ specificity.

"Spontaneous" lung metastases develop in over 50% of the animals bearing subcutaneous isografts of WB-2054, a rat colon carcinoma. A metastatic variant has been developed by "Fidler" type in vivo selection, yielding 100% lung metastasis. In a five-week assay to test the organ specificity of this lung metastatic variant, however, "experimental" liver and lung metastases could be induced in 100% and 60% of animals on portal venous and intravenous injections, respectively. The results demonstrate selection of a metastatic variant from heterogeneous primary tumor, and suggest at least two interacting mechanisms: (1) mechanical (the anatomy of the blood-borne metastatic pathways) and (2) biologic (factors intrinsic to primary tumor subpopulations that can be selected for metastatic proclivity). In addition, liver metastases were successfully established from colon tumors induced by cecal wall injection of tumor cells. Such a spontaneous liver metastasis model will be useful to study the specific mechanisms involved during metastasis of colon cancer to the liver.