The Potential of Glycyrrhiza from "Medicine Food Homology" in the Fight against Digestive System Tumors.

Glycyrrhiza has a long history of applications and a wide range of pharmacological effects. It is known as the "king of all herbs". Glycyrrhiza is effective in clearing heat, detoxifying, relieving cough, and tonifying qi and has good bioactivity in multiple inflammatory, immune, and tumor diseases. This review aims to summarize the origin, distribution, and anti-digestive system tumor mechanism of glycyrrhiza and its homologous applications in medicine and food. The active compounds include triterpenoids, flavonoids, and coumarins, which are widely used in clinical treatments, disease prevention, and daily foods because of their "enhancement of efficacy" and "reduction of toxicity" against digestive system tumors. This paper reviews the use of glycyrrhiza in digestive system tumors and provides an outlook on future research and clinical applications.

Ziyuglycoside II inhibits the growth of digestive system cancer cells through multiple mechanisms.

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.

[Evaluation of drug interactions in patients treated for a lung or digestive cancer]. / Évaluation des interactions médicamenteuses chez des patients traités pour un cancer pulmonaire ou digestif.

INTRODUCTION: Cancer patients are particularly at risk for drug interactions. However, in oncology, this risk has not been studied in depth in France. The main objective of this study was to describe the proportion of drug interactions in patients with lung or digestive cancer. METHODS: The drug prescriptions of 93 patients were analyzed from may 27th, 2019 to July 07th, 2019 using two software programs (Thériaque™ and DDI Predictor™) in oncology patients hospitalized in our comprehensive cancer center. RESULTS: Of the 88 patients included in the study, 544 drug interactions were identified, in 66 patients (75.0%, 95% CI: 64.6-83.6). For 20/88 patients (22.7% CI: 14.5-32.9) a non-recommended combination or a theoretical contraindication was reported. Etoposide was the anticancer molecule most involved in combinations that are contraindicated or not recommended. No combinations defined as not recommended or contraindicated were observed in any of the 49 patients treated with chemotherapy during their hospitalization. The most common toxicities were alertness and metabolic disorders, including hyperkalemia. The use of three or more drugs was a risk factor for drug interactions (83 vs. 23%, P<0.001). CONCLUSION: Drug interactions remain a major concern in cancer hospitalized patients. It is important to continue and strengthen the collaboration between physicians and pharmacists in order to better prevent their occurrence.

Kanglaite injection plus fluorouracil-based chemotherapy on the reduction of adverse effects and improvement of clinical effectiveness in patients with advanced malignant tumors of the digestive tract: A meta-analysis of 20 RCTs following the PRISMA guidelines.

BACKGROUND: The digestive tract malignancies are a series of malignant tumor with high morbidity and mortality. Traditional Chinese medicine (TCM) combined with chemotherapy drugs interventions have been applied for the treatment of malignant tumors in Asian countries for dacades. This study aimed to assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for treating digestive tract malignancies. PURPOSE: To assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for digestive tract malignancies. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when conducting the meta-analysis. Randomized controlled trials (RCTs) of Kanglaite injection combined with fluorouracil-based chemotherapy in the treatment of digestive tract malignant tumors were selected and assessed for inclusion. RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for meta-analysis. The objective response rate (ORR) was defined as the primary endpoint, and the disease control rate (DCR), quality of life (QoL), and toxicities were the secondary outcomes. RESULTS: 20 RCTs enrolling 1339 patients with advanced digestive tract malignancies were included. The methodological quality of most included trials was low to moderate. Compared with fluorouracil-based chemotherapy alone, Kanglaite injection plus fluorouracil-based chemotherapy can improve DCR (risk ratio (RR) = 1.18, 95% confidence interval (CI) 1.11-1.25, P < .00001), ORR (RR = 1.35, 95% CI 1.18-1.54, P < .00001), QoL (RR = 1.58, 95% CI 1.35-1.85, P < .00001), and can reduce adverse drug reactions (ADRs) such as myelosuppression (RR = 0.33, 95% CI 0.25-0.43, P < .00001), leukopenia (RR = 0.31, 95% CI 0.22-0.43, P < .00001), thrombocytopenia (RR = 0.6, 95% CI 0.38-0.49, P = .03), neutropenia (RR = 0.26, 95% CI 0.12-0.55, P = .0005), anemia (RR = 0.41, 95% CI 0.23-0.75, P = .004), gastrointestinal reaction (RR = 0.35, 95% CI 0.27-0.46, P < .00001), nausea/vomiting (RR = 0.41, 95% CI 0.28-0.61, P < .00001), diarrhea (RR = 0.34, 95% CI 0.18-0.62, P = .0004), hepatotoxicity (RR = 0.28, 95% CI 0.17-0.47, P < .00001), neurotoxicity (RR = 0.58, 95% CI 0.41-0.82, P = .002), mucositis (RR = 0.59, 95% CI 0.29-1.21, P = .15). CONCLUSION: Kanglaite injection combined with fluorouracil-based chemotherapy could remarkably improve the clinical effectiveness and reduce the adverse effects in patients with advanced malignant tumors of the digestive tract which may provide evidence to judge whether TCM is an effective and safe intervention for the digestive tract malignancies.

Associations between Omega-3 Fatty Acid Supplementation and Anti-Inflammatory Effects in Patients with Digestive System Cancer: A Meta-Analysis.

Purpose: Patients with digestive system cancer frequently over-express inflammatory cytokines after surgical operations or chemotherapy. Omega-3 fatty acids are key nutrients with numerous beneficial anti-inflammatory effects in cancer patients. The anti-inflammatory effect of supplementation with omega-3 fatty acids in patients with digestive system cancer requires further validation.Methods: The meta-analysis includes studies that compared the variations in inflammatory marker (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein (IL-6, TNF-α, and CRP)) concentrations between patients with digestive system cancer who were supplemented with omega-3 fatty acids versus controls who were not supplemented with omega-3 fatty acids.Results: Our findings indicated that the variations in the IL-6 and CRP concentrations in patients with digestive system cancer did not differ between the supplementation groups and the controls. Statistically significant differences in the variations in the TNF-α concentrations were observed between the supplementation groups and the controls. However, there were no significant differences in the variations in the TNF-α concentrations according to the subgroup analysis.Conclusions: Omega-3 fatty acids may have an inhibitory effect on postoperative TNF-α elevation in patients with digestive system tumors, but additional supporting data require a large clinical trial.

Patients' perception and attitude to totally implantable venous access for urologic or digestive cancer: A cross-sectional study.

INTRODUCTION: Totally implanted venous access (TIVA) improves the safety and welfare of patients treated with cancer chemotherapy (CCT). We aimed to evaluate patients' perception of TIVA placement, TIVA use, and information on TIVA, and to assess the association between patients' perception and their attitude regarding a potential TIVA re-implantation. METHODS: We conducted a single center cross-sectional survey in a university hospital in Northern France. Patients included were consecutive urologic or digestive cancer inpatients admitted for a CCT cycle via TIVA between April 9th and May 9th 2014. We analyzed patients' satisfaction, experience, and attitude, especially when requiring potential TIVA re-implantation under local anesthesia (LA), using a standardized questionnaire and medical records. We analyzed risk factors for refusing potential TIVA re-implantation under LA using multivariate logistic regression. RESULTS: Eighty-one patients were interviewed (no refusals), including 57 with a TIVA device placed under LA in our university hospital. Among them, 52/57 (91%) reported satisfactory TIVA placement, but respectively 21/57 (37%) and 18/57 (32%) complained of painful or uncomfortable TIVA placement; 51/57 (89%) were satisfied with care provided during CCT cycles. Risk factors for refusing potential re-implantation under LA were: TIVA placement considered painful (P=0.012) or uncomfortable (P=0.038) and dissatisfaction with care provided during CCT cycles (P=0.028). DISCUSSION: We show that despite good overall satisfaction regarding TIVA, some aspects were less positive and warrant improvement actions. It suggests that these actions could not only improve patients' experience of TIVA use but could also facilitate continuation of treatment in the long term.

Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy.

BACKGROUND: Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60-80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin. METHODS: Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: "cases" developed oxaliplatin-induced grade 3-4 neuropathy (n = 48), and "controls" (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated. RESULTS: We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16-0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673. CONCLUSION: SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.

[Therapeutic drug monitoring of 5-fluorouracil after its administration in high-dose protocols]. / Niveau de preuve du suivi thérapeutique pharmacologique du 5-fluorouracile au décours de son administration dans le traitement des cancers des voies aérodigestives supérieures et du cancer colorectal.

Therapeutic drug monitoring is currently investigated in patients receiving the drug by prolonged continuous infusion, either alone or associated with other chemotherapy agents. This arises from an increasing body of evidence that relates plasma fluorouracil concentrations to toxicity or effectiveness. Literature data indicate that threshold levels of exposure, as assessed by the area under the concentration-time curve, are associated with an increased risk of toxicity in patients treated for either a colorectal or a head and neck cancer. Kinetically guided dose adjustment may thus be proposed for the ongoing or the next cycle of chemotherapy. Historical comparisons and the results of a phase III multicenter randomized study in patients with metastatic colorectal cancer showed that dose-adapted fluorouracil resulted in significantly improved objective response rate, a trend to higher survival rate and fewer grade III-IV toxicities. Real-time fluorouracil monitoring may also help identifying patients with higher than expected exposure, thus providing a basis for intensifying supportive care in these patients.

Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies.

PURPOSE: The botanical formulation, PHY906, has been used widely in Eastern countries to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. PHY906 may also have anti-tumor properties and may potentiate the action of several chemotherapeutic agents based on pre-clinical studies. We conducted a Phase I study using PHY906 in combination with capecitabine in patients with advanced pancreatic and gastrointestinal malignancies to determine the maximum tolerated dose (MTD) of capecitabine in combination with PHY906. PATIENTS AND METHODS: This study was a single institution, open-label, Phase I study of PHY906 800mg BID on days 1-4 in combination with escalating doses of capecitabine (1000, 1250, 1500, and 1750mg/m(2)) orally twice daily on days 1-7 of a 14-day cycle (7/7 schedule). Capecitabine was increased until the appearance of dose limiting toxicities (DLTs). Measurements of efficacy included tumor response by Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-four patients with a median age of 67 years (range 40-84) with pancreatic cancer (15), colon cancer (6), cholangiocarcinoma (1), esophageal cancer (1) and unknown primary (1) received a total of 116 cycles (median 5 cycles; range 1-17 cycles) over 4 dose levels of capecitabine. One DLT (Grade 4 AST/ALT, Grade 3 hyponatremia) was observed in the 1000mg/m(2) cohort of patients. No further DLT was observed in the subsequent cohorts and doses of capecitabine were escalated to 1750mg/m(2) BID. There were no DLTs at the maximum dose level of 1750mg/m(2), however, the delivered dose-intensity of capecitabine was similar at the 1750mg/m(2) dose level as the 1500mg/m(2) dose level. Therefore, the MTD was defined at 1500mg/m(2) of capecitabine in this dosing schedule with PHY906. One patient achieved a partial response, and 13 patients had stable disease that lasted more than six weeks. CONCLUSION: The MTD of capecitabine was determined to be 1500mg/m(2) BID administered in a 7/7 schedule, in combination with PHY906 800mg BID on days 1-4. This combination was well tolerated and warrants further study.

Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors.

Somatostatin receptor imaging (SRI) with [(111)In-DTPA(0)]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [(68)Ga-DOTA(0),Tyr(3)]octreotate or [(68)Ga-DOTA(0),Tyr(3)]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all (111)In-, (90)Y-, or (177)Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [(90)Y-DOTA(0),Tyr(3)]octreotide and [(177)Lu-DOTA(0),Tyr(3)]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

Supplements for immune enhancement in hematologic malignancies.

This brief review aims to discuss the various cellular immunological aspects and related mechanisms of the use of specific components from traditional herbal medicines. We begin with lessons learned from thalidomide as an effective single drug with multiple mechanisms of action to treat multiple myeloma. Examples of "supplements" or integrative therapy will be drawn from arsenic trioxide, medicinal mushrooms including Coriolus vesicular and Ganoderma lucidum, followed by the discussion of beta-glucans affecting various immunological important cellular subsets. Different classes of compounds may enhance distinct immune cell populations that might contribute to a multi-targeted holistic effects on anti-cancer treatment. Finally, we conclude by highlighting an herbal formulation PHY906 as a potential adjunct to chemotherapy that might become one of the first US Food and Drug Administration (FDA) approved oral herbal medicines for anti-cancer adjunct treatment.

The role of capecitabine in the management of tumors of the digestive system.

Capecitabine has been developed as a prodrug of FU, with the goal of improving tolerability and intratumor drug concentration through tumor-specific conversion to the active drug. The purpose of this article is to review the available information on capecitabine with respect to clinical efficacy for tumors of the digestive tract, adverse-effect profile, documented drug interactions, dosage and administration, and future directions of ongoing research. Relevant English-language literature was identified through searches of NCI, PubMed, ASCO.org and ESMO, ECCO meetings proceedings.

Cytotoxic effects of haplamine and its major metabolites on human cancer cell lines.

Haplamine, extracted from Haplophyllum perforatum, is widely used in Central Asia for treating various diseases, including testicular cancer. The purpose of the present study was to investigate in vitro the cytotoxic properties of haplamine and its major metabolites (trans/cis-3,4-dihydroxyhaplamine) on human pancreatic cancer, colorectal cancer and hepatic cancer cell lines. The efficacy of haplamine was compared with those of the respective reference drugs for treating digestive cancers (e. g., 5-FU, gemcitabine). Finally, the implication of apoptosis in haplamine-induced cell death was investigated. The IC50 values of of haplamine were 52.5 +/- 2.6, 24.3 +/- 0.7; 41.5 +/- 2.5, 72 +/- 2, 32 +/- 2.2 and 59.7 +/- 2.1 microM in human pancreatic cancer (Capan1 and Capan2), colorectal cancer (LS174T, HT29, and SW620) and hepatic cancer (HepG2) cells, respectively. The IC50 values of trans/cis-3,4-dihydroxyhaplamine were both > 200 microM, thus suggesting that the previously reported cytotoxic efficacy of haplamine was supported by the parent drug only. Besides, our data showed that haplamine leads to cell death through the induction of early/late apoptosis in the target cells. Interestingly, we found that haplamine showed significant antiproliferative efficacy on resistant SW620 colorectal cells, whereas the reference drug 5-FU was ineffective (32 vs. 73 microM, p < 0.01 t- test), thus suggesting that haplamine could be of interest for treating digestive cancers resistant to standard fluoropyrimidines. Similarly, haplamine proved to be significantly more potent in pancreatic cells than gemcitabine, the reference cytotoxic drug for treating pancreatic carcinomas. Overall, these results confirm the anticancer properties of haplamine suggested by its traditional use, and indicate that it could be further considered in various other solid tumours frequently encountered in adults, including those resistant to standard chemotherapy.

Sirolimus and intraoperative hyperthermic peritoneal chemoperfusion with mitomycin-C do not impair healing of bowel anastomoses.

Surgeons will increasingly have to address the development of gastrointestinal disease in transplant patients or deal with extended bowel resection and bowel anastomosis in advanced cancer patients. Immunosuppressants as well as intraoperative hyperthermic peritoneal chemoperfusion (IHPC) may alter intestinal anastomotic healing. We evaluated the effects of the immunosuppressant sirolimus and of IHPC on healing and stability of bowel anastomoses in pigs. Twenty-four pigs were divided into four groups (SIR: sirolimus was administered orally; IHPC: animals received IHPC with mitomycin-C; COMP: combination of sirolimus and IHPC was administered; CON: sham-treated control group). Animals underwent hand-sutured small bowel and left colon anastomoses and were killed on postoperative day 4. Anastomoses were evaluated by morphometric analysis and immunohistochemistry (IHC) and by measuring the bursting pressure (BP). In all experimental groups (SIR, IHPC, COMP), anastomotic BPs remained unaltered and were not statistically different compared with control (CON). In addition, ileum villous height and colonic crypt depth analysis revealed no significant difference in mucosal thickness, and IHC showed no difference among groups in proliferation, as assessed by the number of KI-67- and bromodeoxyuridine-labeled cells. Immunosuppression with sirolimus as well as IHPC with mitomycin-C do not alter healing of intestinal anastomosis in pigs.

Induction of apoptosis in HepG2 cells by solanine and Bcl-2 protein.

The nightshade (Solanum nigrum Linn.) has been widely used in Chinese traditional medicine as a remedy for the treatment of digestive system cancer. The anti-tumor activity of solanine, a steroid alkaloid isolated from the nightshade has been demonstrated. To observe the effect of anti-tumor and mechanism of solanine. The MTT assay was used to evaluate the IC(50) on the three digestive system tumor cell lines. The effect on the morphology was observed with a laser confocal microscopy; the rate of apoptosis and the cell cycle were measured using flow cytometry (FCM); the expression of Bcl-2 protein was measured by Western blot. The results show that the IC(50) for HepG(2), SGC-7901, and LS-174 were 14.47, >50, and >50 microg/ml, respectively; the morphology of cells in the negative control was normal; for the treated groups, typical signs for apoptosis were found. The rate of apoptosis in HepG(2) cells induced by solanine was found to be 6.0, 14.4, 17.3, 18.9, and 32.2%, respectively. Observation of the cell cycle showed that cells in the G(2)/M phases disappeared while the number of cells in the S phase increased significantly for treated groups. Western blot showed that solanine decreased the expression of Bcl-2 protein. Therefore, the target of solanine in inducing apoptosis in HepG(2) cells seems to be mediated by the inhibition in the expression of Bcl-2 protein.

Progress in research on applying Sijunzi Decoction in treating digestive malignant tumor.

Patients with digestive malignant tumor always have their immune function, especially the cellular immunity, suppressed to a certain extent. Traditional Chinese medicine (TCM) holds that Pi-Wei is the essence of postnatal life, and the genesis and development of digestive tumor are chiefly due to the insufficiency of vital-qi, which makes the body open to the invasion of evil pathogens. Starting from regulating the immune function of organisms, researchers recently obtained some therapeutic effects by applying the Chinese recipe, Sijunzi Decoction, in the treatment of digestive malignant tumors. In this paper, the related studies on the concerned basic theory and clinical application were reviewed.

In vitro anticancer activity of aqueous extracts and ethanol extracts of fifteen traditional Chinese medicines on human digestive tumor cell lines.

The purpose of this study was to investigate the anticancer activity of 15 traditional Chinese medicines which are usually used for tumor patients in China. The MTT (methylthiazolyldiphenyl-tetrazolium bromide) method was applied to compare the antitumoral activity of the aqueous crude extracts and the ethanol crude extracts of these drugs on six human digestive tumor cell lines: human liver carcinoma cell lines (HepG-2 and SMMC-7721), human gastric cancer cell line (BGC-823), human colon adenocarcinoma cell lines (LoVo and SW-116) and esophagus adenocarcinoma cell line (CaEs-17). Most ethanol extracts demonstrated a more powerful inhibitory effect than aqueous extracts. Their IC50 values were between 10 microg/mL and 500 microg/mL. Among these drugs, Paris polyphylla Smith showed a predominant inhibitory effect on all the cell lines with IC50 values ranging from 10 microg/mL to 30 microg/mL. The findings in this study suggested that traditional Chinese medicines, especially Paris polyphylla Smith, might have potential anticancer activity on digestive cancer and its mechanism needs further study.

Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients.

BACKGROUND: It is assumed that perioperative immunomodulation of cancer patients can attenuate cellular and humoral deficiencies thus improving their overall health status. Mistletoe (Viscum album L.) anticancer drugs are likely candidates for such adjuvant therapy, because they do not have major adverse side-effects but have dual desirable activities; immune-modulating effects and relatively selective cytotoxicity for cancer cells. MATERIALS AND METHODS: We used the aqueous extract Isorel, which is produced from the entire plant and is validated for batch consistency. The study involved 70 cancer patients, divided into two groups: Isorel-treated group of 40 patients who received Isorel for 2 pre- and 2 post-operative weeks (1 esophageal, 16 gastric, 2 pancreatic and 21 colorectal carcinomas) and the age- and sex-matched control group of 30 patients that did not receive Isorel (2 esophageal, 9 gastric, 3 pancreatic, 1 ileac and 15 colorectal carcinomas). Blood samples were obtained to study parameters of the immune system before the surgery and the drug administration (DO) and on the postoperative days 1 and 14 (D1, D14). The overall health status was evaluated after 60 days by the Kamofsky Performance Index and by the Analogic Scale of Anxiety. The results were compared by Student's t-test and one-way ANOVA test. RESULTS: Isorel significantly attenuated the immuno-suppressive effects of surgery observed for the Isorel-treated group, increasing the number of NK cells, the T and B cells, in particular T-helper cells, complement, IgA, IgG and IgM values also in comparison to the respective D0 values. Both the Kamofsky status and the Anxiety Scale improved remarkably in Isorel-treated patients in comparison to the control. CONCLUSION: The results of this study indicate that perioperative use of the mistletoe drug Isorel can improve immune competence and the overall health status of cancer patients undergoing surgery.