Size-mediated effects of climate on tree growth and mortality in Mediterranean Brutia pine forests.

The Eastern Mediterranean Basin is experiencing long-term drought conditions that affect the growth and mortality of many forest tree species. We analysed tree rings from 113 Pinus brutia (living and dead) trees of different age (<50, 50-85, >85 years old) and size to study how climatic variation during the 20th century has shaped their radial-growth and mortality patterns. We selected the pine forest on the island of Lesvos (Greece) representing the largest continuous P. brutia forest on the Aegean islands, to develop a chronology that could provide a bridge between the available tree-ring data sets from the Western and Eastern Mediterranean region. The analysis of the novel chronology captured well-known drought events during the 20th century, such as those in 1949, 1990 and 2007, and provided an equation to reconstruct the intensity of droughts (10 month time scale). P. brutia tree-growth indicated a positive trend from the beginning until the 3rd quarter of the 21st century and then flattened for living trees. Trees that eventually died between 2010 and 2019, were characterized by a much lower growth than surviving trees and also illustrated a long-lasting negative growth trend. Precipitation and water availability (inferred from the SPEI drought index) were positively related to the growth of living and dead trees, mainly in the middle and old age classes. Temperature effect on tree growth shifted from negative to positive with increasing age of living trees, but remained always negative across all age classes in trees that eventually died. Our findings verify the positive effect of water availability on tree growth and survival of Mediterranean pines and highlight a size-mediated effect of temperature on tree growth, probably coupled with individual-tree access to underground water resources. Increased air temperatures during various time periods related to tree physiological activity seem to negatively affect tree survival across all age classes, in Mediterranean P. brutia forests, highlighting their potential vulnerability to global warming conditions.

Vaccine third dose and cancer patients: necessity or luxury?

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.

Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

ABREAST: a prospective, real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and quality of life of patients with metastatic breast cancer.

PURPOSE: The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. PATIENTS AND METHODS: The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. RESULTS: Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6-33.7], the median PFS was 6.2 months (95% CI 5.2-7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients' baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. CONCLUSIONS: This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.

Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.

Efficacy and tolerance of frontline bevacizumab-based chemotherapy for advanced non-small cell lung cancer patients: a multicenter, phase IV study of the Hellenic Oncology Research Group (HORG).

INTRODUCTION: The addition of bevacizumab to the first-line chemotherapy of advanced non-small cell lung cancer (NSCLC) of non-squamous histology has been shown to improve survival. A multicenter, single-arm, phase IV study was conducted in order to evaluate the efficacy and toxicity of frontline bevacizumab-based chemotherapy regimens in real life. METHODS: Patients with previously untreated recurrent or metastatic non-squamous, NSCLC, with no contraindications for bevacizumab, were enrolled. Bevacizumab (15 mg/kg every 3 weeks) was administered in combination with both platinum- and non-platinum-based chemotherapy doublets or with single-agent chemotherapy plus bevacizumab. Treatment with bevacizumab was continued until disease progression. The primary end point of the study was the safety profile of bevacizumab regimens, whereas the secondary end points included overall survival, progression-free survival, and overall response rate. RESULTS: From February 2010 to April 2014, a total of 314 patients were enrolled in the study; the median age was 63, 74.8 % were men, 95.9 % had a performance status of 0-1, 90.4 % had metastatic disease, and 94.3 % had adenocarcinoma. Grade ≥3 neutropenia occurred in 11.5 % of the patients, 1.3 % experienced febrile neutropenia, 2.6 % grade ≥3 thrombocytopenia, 2.8 % thromboembolism, and 1.6 % severe bleeding. Treatment discontinuation occurred in 7.0 % of patients because of adverse events. There were three toxic deaths. Median progression-free survival was 7.7 months, and median overall survival was 17.6 months. CONCLUSION: The combination of bevacizumab with chemotherapy in the first-line setting of NSCLC is safe and active when used in appropriately selected patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01934465.

Performance of three small-scale wastewater treatment plants. A challenge for possible re use.

The study focused on the assessment of the performance of three WWTPs in Greece by the estimation of the microbiological and chemical quality of influent and effluent sewage. Physicochemical parameters were recorded (temperature, pH, COD, BOD, suspended solids, conductivity), and meteorological data were collected (air temperature, rain). Microbiological parameters were analyzed (Escherichia coli, total coliforms, bacteriophages, Salmonella, human adenoviruses, Candida, Pseudallescheria boydii, helminths, parasites Cryptosporidium ssp., and Giardia spp.). Statistically significant correlations among the various aforementioned parameters were investigated, in an attempt to propose appropriate processing performance indicators. Furthermore, the study aimed to assess current joint ministerial decision (JMD) on wastewater reuse, for irrigation purposes; to evaluate its practicability and its potential for public health protection. In the vast majority, outlet samples from all three studied WWTPs were not appropriate for irrigation reuse purposes based on BOD50 and suspended solids limit values, set by the current JMD, for both limited and unrestricted irrigation applications. Reductions for E. coli, total coliforms, and bacteriophages were found to range between 2-3, 1.5-2.5, and 2-4 log10 values, respectively. Salmonella spp. was detected in outlet sewage samples from Patra (PAT), Arachova (ARH), and Livadeia (LEV), at 23% (3/13), 33% (4/12), and 38% (5/13), respectively. Molds were detected at 92.3% (12/13), 100% (13/13), and 91.6% (11/12), respectively, while Candida was found at 85% (11/13), 67% (8/12), and 46% (6/13). A high prevalence of Pseudallescheria boydii, in outlet samples from all studied WWTPs is an important public health issue, which underlines the need for further studies on this emerging fungal pathogen in wastewater reuse applications. Pseudallescheria boydii was found at 85% (11/13), 67% (8/12), and 46% (6/13), respectively. Helminths were found in both inlet and outlet samples, of all studied WWTPs, at 100%. Human adenoviruses, were detected at high percentages in outlet samples at 76.9% (10/13), 92.3% (12/13), 84.6% (11/13), respectively, while no influence of UV irradiation was recorded on the entry and exit loads of human adenoviruses. No influence of meteorological parameters was found on the microbiological and chemical parameters, with the exception of a weak positive correlation between environmental temperature and bacteriophages. A moderate positive correlation was found between BOD and suspended solids, bacteriophages, and total coliforms, bacteriophages and E. coli, and bacteriophages and adenoviruses. A significant positive correlation was found between total coliforms and E. coli, COD and BOD, and suspended solids and COD. No correlations were proved between human pathogens and bacterial indicator parameters. Collectively, our findings underlined the unsuitability of the current JMD on wastewater reuse in Greece, or public health protection. The study is expected to support the development of a public health risk assessment model based on quantitative risk assessment on the use of treated wastewater for irrigation purposes in Greece.

Cisplatin in combination with metronomic vinorelbine as front-line treatment in advanced non-small cell lung cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG).

PURPOSE: To evaluate the safety and efficacy of metronomic vinorelbine in combination with cisplatin as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 41 patients with inoperable stage IIIb or stage IV NSCLC (14 with adenocarcinomas, 19 with squamous cell carcinoma and eight with other types), PS = 0-2, were treated with cisplatin (80 mg/m(2)) in combination with oral metronomic vinorelbine (60 mg total dose, every other day) in cycles of 21 days. RESULTS: A total of 35 patients who received at least one cycle of chemotherapy were evaluable for toxicity and response. Partial response was achieved in 13 patients (ORR 37.1%; CI 21.1-53.1%) and stable disease in 10 (28.6%). After a median follow-up period of 26.2 months (range 0.5-33.4 months), the median progression-free survival was 4.2 months and the median overall survival 12.0 months. The 1-year survival rate was 52.6%. Myelosuppression was the main adverse event with grade 3 and 4 neutropenia occurring in five (14.3%) and six (17.1%) patients, respectively. Three of these patients presented with febrile neutropenia and there was one death due to sepsis. Non-hematologic toxicities were mild. CONCLUSION: Cisplatin in combination with metronomic vinorelbine is an active, although myelotoxic, therapeutic option in the first-line setting for the treatment of patients with locally advanced and metastatic non-small cell lung cancer, which merits further evaluation in randomized trials.

Frontline treatment with gemcitabine, oxaliplatin and erlotinib for the treatment of advanced or metastatic pancreatic cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG).

PURPOSE: Intravenous gemcitabine is the standard of care for patients with metastatic cancer of the pancreas. Gemcitabine-based chemotherapy combinations, either doublets or triplets, have been tested in the past but have offered a small advantage (Brodoefel et al. in Eur J Radiol 73:594-600, 2010). In the present study, we present the results of the triplet gemcitabine-oxaliplatin-erlotinib combination as firstline treatment in this setting. PATIENTS AND METHODS: Seventy-one eligible patients were included in this study. All patients received chemotherapy with gemcitabine (1,100 mg/m(2) on days 1 and 8) plus oxaliplatin (130 mg/m(2) on day 8) and erlotinib (100 mg p.o./day for 21 days). The treatment cycle was 21 days. RESULTS: Partial response was achieved in 15 patients (21%; 95% CI 11.63-30.62) and stable disease in 15 patients (21%). Forty-one patients (57.8%) experienced disease progression. Median progression-free survival was 5.2 months (range 0.6-34.7; 95% CI 3.71-6.76). The median overall survival was 10.5 months (95% CI 7.39-13.61) and the 1-year survival estimate 47.3%. The main adverse events were grade 3/4 anemia occurring in three (4.2%) patients and grade 3 and 4 thrombocytopenia occurring in eight (11.3%) and three (4.2%) patients, respectively. Grade 4 neutropenia was rare (1.4%), and one patient presented febrile neutropenia. CONCLUSION: This study demonstrated that the combination of gemcitabine, oxaliplatin and erlotinib is active, well tolerated and safe for patients with metastatic adenocarcinoma of the pancreas. However, the results do not seem to be better than those reported with chemotherapy alone.

The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study.

PURPOSE: Ovarian cancer is the leading cause of death from gynecological cancer. The current treatment of this type of cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if the hyperthermic intraoperative chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second or third line systemic chemotherapy. METHODS: Forty-eight patients suffering from advanced ovarian cancer (FIGO stages III and IV) who recurred after initial treatment with conservative or debulking surgery and systemic chemotherapy were included in this study. Twenty-four patients (group A) were treated with CRS followed by HIPEC and then systemic chemotherapy. Due to various reasons the remaining 24 patients (group B) were treated with CRS and systemic chemotherapy alone. RESULTS: The median survival for group A was 19.4 months vs. 11.2 months in group B (p <0.05). One-year survival was 85% in group A vs. 35% in group B (p <0.05). The 3-year survival rate was 50% in group A vs. 18%. in group B (p <0.01). The resection status was found to be a significant predictor of overall survival (p <0.05). Patients with peritoneal cancer index (PCI) score < 15 appeared also to have longer survival. CONCLUSION: The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with a recurrence in an initially advanced ovarian cancer.

Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis.

PURPOSE: Peritoneal carcinomatosis (PC), which has been regarded as a lethal condition, may now be treated, achieving a long-term disease-free survival with cytoreductive surgery by treating macroscopic tumor seeding and hyperthermic intraperitoneal chemotherapy (HIPEC) by treating residual microscopic disease. The purpose of this study was to analyse the morbidity and mortality of this procedure. METHODS: A total of 39 consecutive patients were included in this retrospective study. After complete resection of the PC, HIPEC was performed via the coliseum technique. The chemotherapeutic agents used depended on the tumors' histology. RESULTS: Postoperative mortality and morbidity rates were 5.1%% (2/39) and 43.5% (17/39), respectively. The most frequent complications were pulmonary complications (31%), gastrointestinal fistulas (20%), hematologic toxicity (16%) and postoperative bleeding (11%). Statistical correlations were evidenced between morbidity and PC index (p<0.004), duration of surgery (p<0.001) and blood loss (p<0.001). CONCLUSION: This approach has resulted in a relatively high but acceptable percent of adverse events considering the expected advantage for survival.

Colorectal carcinoma: contribution of growth pattern on prognosis.

BACKGROUND: Recent studies have reported poor prognosis in colorectal carcinomas with non-polypoid growth pattern. The aim of the present study is to investigate this issue in the patients referred to "Hatzikostas" General Hospital of Messolonghi, Greece. MATERIALS AND METHODS: A total of 13 patients who were treated for primary colorectal adenocarcinoma in a one-year period were studied. Colorectal carcinomas were classified into two types based on the presence or absence of elevation of tumour as compared with adjacent mucosa: polypoid growth (PG-type) and non-polypoid growth (NPG-type) carcinomas. Clinical and tumour histopathologic parameters were analysed. RESULTS: Unlike PG-type carcinomas, NPG-type carcinomas had a high proportion of poorly differentiated adenocarcinoma cells, a high likelihood of being advanced, and a high frequency of lymph node as well as distant metastases at the time of diagnosis. CONCLUSIONS: Colorectal carcinomas with NPG pattern tend to show more malignant characteristics than those with PG pattern, explaining their poorer outcome.

The presence and significance of iron in neoplasia of the colorectum.

BACKGROUND: To investigate the presence and distribution of tissue iron in colon adenomas of all grades of dysplasia as well as colorectal carcinomas of all grades of differentiation. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue blocks from 8 biopsies of colon adenomas and 13 surgical specimens of colorectal carcinoma were studied. Consecutive sections were stained using Perls' stain that demonstrates the presence of ferric iron by staining it blue. RESULTS: Iron was absent in all cases of colon adenoma. On the other hand, iron was present in 9 of the 13 cases of colorectal carcinoma (69.23%), regardless of the degree of differentiation, the location and the stage of development. The iron was stored in mesenchymal cells in the stroma and various types of inflammatory cells. CONCLUSIONS: Our results suggest association of iron presence in the environment of malignant cells. Thus, iron may be a carcinogenic factor, possibly facilitating tumour growth and modulating local immune response.

Chemotherapy in metastatic colorectal cancer.

The treatment of patients with metastatic colorectal cancer (MCRC) has changed dramatically over the years. 5-Fluorouracil (5FU)-based therapies have been routinely included in treatment regimens for colorectal cancer for the past 40 years. A number of options are available to clinicians for the treatment of patients relapsing after surgical excision of their primary tumour, such as 5FU in association with FA, the new drugs such as irinotecan and oxaliplatin and the oral fluoropyrimidines: capecitabine and uracil/tegafur (UFT). It has been shown that combination therapy with 5FU/FA and irinotecan or oxaliplatin is more active than 5FU/FA in the first line of treatment in MCRC. New agents acting on novel targets are under development such as epidermal growth factor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase 2 inhibitors.

Sandostatin as a "hormonal" temporary protective ileostomy in patients with total or subtotal colectomy.

BACKGROUND/AIMS: We describe our experience with the use of a new method of so-called "hormonal" ileostomy by using Octreotide, a long-acting analog of the inhibitory peptide Somatostatin (Sandostatin Novartis), aiming to advocate protective ileostomy or colostomy, in patients who underwent total or subtotal colectomy for ulcerative colitis or obstruction of left colon, due to carcinoma or diverticulitis. METHODOLOGY: "Hormonal" protective ileostomy by using Sandostatin (Novartis) was performed in 10 patients after subtotal colectomy for ulcerative or left colon obstruction without a protective ileostomy or colostomy. Sandostatin 0.5 mg/mL was given from the day of operation to the 10th postoperative day, in a dose of 2 x 3 per day subcutaneously. The time of return of peristalsis, number of bouts of diarrhea and postoperative complications were evaluated. RESULTS: The patients were classified in two groups: First group (40% of all patients) with bowel obstruction and second group (60% of all patients) with ulcerative colitis. In the first group the mean time of return of peristalsis was 4.5 days and the mean number of bouts of diarrhea was 4.2 per day. One patient was reoperated for intraabdominal abscess and the morbidity was 50% with minor postoperative complications. In the second group the mean time of peristalsis return was 5 days and the mean number of bouts of diarrhea was 5.4 per day. One patient was reoperated for intestinal bleeding and the morbidity was 60% with minor postoperative complications. CONCLUSIONS: The use of Octreotide appears to serve as a useful adjunctive and important role in controlling intestinal output, so that it is an available method of "hormonal" protective ileostomy in very low rectal or anal anastomosis, by avoiding a second operation for ileostomy or colostomy closure and reducing the median hospital stay and total socioeconomic cost.

Octreotide Acetate in the Treatment of Fluorouracil-Induced Diarrhea.

Cytotoxic chemotherapy, particularly the regimens that contain 5-fluorouracil (5-FU), can produce diarrhea. Octreotide acetate appears to have a major therapeutic effect in the management of 5-FU-induced diarrhea. A prospective study was conducted to investigate the efficacy of two different doses of octreotide acetate, 100 µg and 500 µg three times daily, for the treatment of severe 5-FU-induced diarrhea refractory to loperamide, and also to evaluate whether the higher dose is more effective in the management of this complication. Fifty-nine patients with tissue-documented colorectal and head and neck carcinoma were enrolled in this study, 28 in the 100 µg arm and 31 in the 500 µg arm of octreotide acetate which was administered s.c. three times daily. Patients were required to have National Cancer Institute Common Toxicity Criteria

The role of hormonal and dietary factors in pancreatic carcinogenesis.

The pancreatic cancer continues to represent an important problem, as a cancer with extremely poor prognosis. To date more than 16 chemicals have been shown to induce pancreatic tumors, in animal models. The tumors developed in rats are essentially of acinar type and those in hamsters mostly of ductal type. Many studies proved the direct or indirect role of hormonal and dietary factors in pancreatic cancer. The development of alternative treatments according to biological and biochemical steps of carcinogenesis is available as adjuvant treatment. We present herein an overview of current experimental and clinical results in order to understand the evolution, histogenesis and biological behaviour of pancreatic cancer.

New role of a medical documentation system.

Architecture of a new medical documentation system (MDS) is proposed. First, we studied the traditional MDS in terms of organizational structure, main functions, means (resources) and personnel. Special emphasis is given to the information retrieval (IR) system which is the kernel of a MDS. Then, some achievements of information technology is summarized, and concept of a mixed IR system which is the kernel of the new system is presented. New architecture is then presented. Units which compose the entire system are: host documentation centre, local documentation centres, and documentation units. Eventually, objective and features of every part are discussed.