Retrolaminar block for opioid-free anaesthesia and enhanced recovery after posterior lumbar discectomy: A randomised controlled study.

Background and Aims: Intraoperative regional analgesia and enhanced recovery are standard care models aimed at reducing perioperative opioid use following spine surgeries. This study aimed to examine the analgesic effect of retrolaminar block in promoting recovery and pain relief after posterior lumbar discectomy. Methods: The patients undergoing elective posterior lumbar discectomy were randomised into the retrolaminar group (n = 36) (received an intra-operative bilateral retrolaminar block with 15 mL of bupivacaine 0.25%, 2 mL (8 mg) of dexamethasone, and 2 mL of magnesium sulphate 10% (200 mg) on each side) and control group (n = 36) (received standard general anaesthesia). Primary outcomes were recovery time (time from isoflurane discontinuation to the first response to verbal command) and time to discharge (time from admission to the post-anaesthesia care unit (PACU) to discharge from the PACU, when Aldrete score was ≥9). P values < 0.05 were considered statistically significant. Results: The extubation, recovery, and discharge times were significantly shorter in the retrolaminar group compared to the control group (P < 0.001). Postoperative pain scores were significantly lower in the retrolaminar group for up to 8 h compared to only 2 h in the control group (P < 0.001). The time to first administration of ketorolac post-operatively was significantly longer in the retrolaminar group compared to the control group (P < 0.001). The total consumption of ketorolac post-operatively was significantly reduced in the retrolaminar group compared to the control group (P < 0.001). Conclusion: Intra-operative retrolaminar block is an easy and effective opioid-free regional anaesthesia technique that improves recovery after posterior lumbar discectomy.

The Analgesic Effects of Preemptive Ultrasound-Guided Pericapsular Nerve Group Block in Comparison with Erector Spinae Plane Block in Elderly Undergoing Hip Arthroplasty: A Randomized Controlled Trial.

Background: Perioperative pain management strategies in the elderly undergoing hip arthroplasty need special and safe preemptive care. Objectives: The primary aim of this study was to compare the analgesic effects of preemptive ultrasound-guided pericapsular nerve group (PENG) block and lumbar erector spinae plane block (L-ESPB) in the elderly undergoing hip arthroplasty. The time to the first postoperative rescue analgesia was measured. The secondary aim was to assess the ease of spinal positioning (EOSP), onset of sensory block, block performance time, and patient satisfaction. Methods: Before positioning for spinal anesthesia, 69 elderly patients undergoing hip arthroplasty were randomized into three groups (n = 23 per group). The first intervention group received ultrasound-guided PENG block with 20 mL bupivacaine 0.25%; the second intervention group received ultrasound-guided L-ESPB using the same dose of bupivacaine. In the control group, patients received spinal anesthesia without any block. Results: The time to first postoperative rescue analgesic (morphine) was significantly prolonged in the PENG group (13.3 ± 3.5 h) compared to the L-ESPB (9.5 ± 2.3 h) and control (2.6 ± 0.4 h) groups. The EOSP score was significantly higher in the PENG group compared to the L-ESPB and control groups (P < 0.001). The block performance time and oneset of the sensory block were significantly shorter in the PENG group compared to the L-ESPB group. The highest patient satisfaction scores were observed in the PENG group. Conclusions: Preemptive pericapsular nerve group block postponed the need for postoperative analgesia and eased spinal positioning compared to L-ESPB in the elderly undergoing hip arthroplasty.

Ultrasound-guided Retrolaminar Block Versus Thoracic Epidural Analgesia for Pain Control Following Laparoscopic Cholecystectomy.

BACKGROUND: Anesthesiologists are always looking for a regional analgesic technique which is easy, safe, has a low complication rate, and provides satisfactory analgesia. A retrolaminar block is a recent modified paravertebral technique for analgesia in  thoracoabdominal procedures with a local anesthetic injected at the retrolaminar site. It has the advantage of being safe and easy compared with traditional thoracic epidural analgesia but is still under investigation. OBJECTIVE: This study aimed to compare ultrasound-guided bilateral retrolaminar block with ultrasound-guided thoracic epidural analgesia for pain relief after laparoscopic cholecystectomy. STUDY DESIGN: A prospective randomized double-blinded clinical study. SETTING: Academic University Hospitals. METHODS: Fifty-two adult patients were randomly allocated into 2 equal groups at the end of the surgery: Group R (n = 26) received a bilateral ultrasound-guided retrolaminar block with 20 mL of 0.25% bupivacaine and 5 µg/mL adrenaline (1:200000) in each side. Group T (n = 26) received ultrasound-guided thoracic epidural analgesia with 20 mL of 0.25% bupivacaine and 5 µg/mL adrenaline (1:200000). RESULTS: The Numeric Rating Scale  scores both at rest and during cough were statistically significantly lower in Group R compared with Group T at 30 minutes and one hour postoperatively. The pain scores were statistically significantly lower for about 4 hours in Group R group compared with 6 hours in Group T. The time for the first call of nalbuphine was highly statistically significantly shorter in Group R group (233.04 ± 5.27 minutes) compared with Group T (353.77 ± 5.16 minutes) (mean difference -120.37, (95% CI,  -123.6 to -117.8) P < 0.001. The total amount of nalbuphine consumption in the first 12 hours was statistically significantly decreased in Group T (17.31 ± 5.52 mg) compared with Group R (27.69 ± 5.52 mg) (Mean difference 10.4, 95% CI  7.3-13.5), P < 0.001. The total number of patients who developed nausea and vomiting were statistically significantly greater in Group T (9 patients) compared with Group R group (3 patients), P = 0.04. Moreover, hypotension was statistically significantly more common among patients in Group T group (10 patients) compared with Group R (3 patients), P = 0.025. Both groups were comparable regarding patient satisfaction. LIMITATIONS: There is limited literature in the field of the present study and sensory dermatome assessment, but this does not affect the results as we used an ultrasound-guided technique. CONCLUSIONS: A single injection retrolaminar block provides adequate postoperative pain relief for about 4 hours compared with a single shot thoracic epidural that lasts about 6 hours. Patient satisfaction with both techniques was the same; about two-thirds of the patients were satisfied or very satisfied with either block.

Effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion and postoperative pain in nasal surgery: a randomized controlled trial.

BACKGROUND: Maintenance of adequate peripheral perfusion during controlled hypotension is necessary for patient safety and improved surgical outcomes during controlled hypotension in nasal surgery. The hypothesis of this study was to investigate the effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion and postoperative pain in patients undergoing nasal surgery. METHODS: A total of 50 patients were randomly assigned into two equal groups in this double-blind clinical study: the magnesium sulfate group; received 40 mg/kg loading dose of intravenous (IV) magnesium sulfate followed by 10-15 mg/kg/h continuous IV infusion and the labetalol group; received 0.25 mg/kg loading dose of IV labetalol followed by 0.5-1 mg/kg/h continuous IV infusion to achieve a mean arterial blood pressure (MABP) of = 55-65 mmHg. The primary outcome was to compare the effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion during nasal surgery. The secondary outcomes were the assessment of serum lactate, postoperative pain, time to the first call for pethidine (rescue analgesic) and total pethidine consumption. RESULTS: PPI was comparable between the groups at baseline, intubation, and 5 min. In contrast, magnesium sulfate group had a significantly higher PPI than the labetalol group. The magnesium sulfate group had a significantly higher MABP and heart rate compared to labetalol group. The time to reach the target MABP was significantly prolonged in magnesium sulfate than the labetalol group [21.6 ± 1.7 vs 6.9 ± 1.5] min. VAS scores were significantly lower for 2 hs postoperatively in the magnesium sulfate group than the labetalol group. The time to first call of pethidine was significantly prolonged in the magnesium sulfate group compared to the labetalol group [113.1 ± 5.2 vs 28.2 ± 1.5] min. CONCLUSIONS: Magnesium sulfate maintains wider PPI and offers better postoperative pain relief compared to labetalol during induced hypotension in nasal surgery. TRIAL REGISTRATION: Institutional review board approval (ref: 6601/20-12-2020). CLINICALTRIAL: gov (ref: NCT04688203 , date of registration: 29 -12-2020).

Nanobiotechnological Approaches to Enhance Drought Tolerance in Catharanthus roseus Plants Using Salicylic Acid in Bulk and Nanoform.

Drought has a detrimental effect on crop production, affecting economically important plants' growth rates and development. Catharanthus roseus is an important medicinal plant that produces many pharmacologically active compounds, some of which have significant antitumor activity. The effect of bulk salicylic acid (SA) and salicylic acid nanoparticles (SA-NPs) were evaluated on water-stressed Catharanthus roseus plants. The results showed that SA and SA-NPs alleviated the negative effects of drought in the treated plants by increasing their shoot and root weights, relative water content, leaf area index, chlorophyll content, and total alkaloids percentage. From the results, a low concentration (0.05 mM) of SA-NPs exerted positive effects on the treated plants, while the best results of the bulk SA were recorded after using the highest concentration (0.1 mM). Both treatments increased the expression level of WRKY1, WRKY2, WRKY40, LEA, and MYC2 genes, while the mRNA level of MPKK1 and MPK6 did not show a significant change. This study discussed the importance of SA-NPs in the induction of drought stress tolerance even when used in low concentrations, in contrast to bulk SA, which exerts significant results only at higher concentrations.

Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale.

PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

Comparative Study Between Dexmedetomidine and Fentanyl as an Adjuvant to Intraarticular Bupivacaine for Postoperative Analgesia after Knee Arthroscopy.

BACKGROUND: Intraarticular bupivacaine produces sufficient analgesia after arthroscopic knee surgery, but its analgesic duration is short. There is a need to search for an adjuvant with a longer duration of analgesia. OBJECTIVES: This study aimed to compare the duration of analgesia, total rescue analgesic consumptions, pain intensity, adverse effects, and patient satisfaction of dexmedetomidine and fentanyl as adjuvants to intraarticular bupivacaine for analgesia after knee arthroscopy. STUDY DESIGN: A prospective double-blind randomized controlled study. SETTING: Zagazig University Hospitals. METHODS: After ending arthroscopy and 15 minutes before deflation of the tourniquet, 45 patients were randomly allocated into 3 equal groups: Group B (n = 15) received an intraarticular injection of 50 mg (20 mL) bupivacaine 0.25% plus 1 mL saline; group BD (n = 15): received an intraarticular injection of 20 mL bupivacaine 0.25% plus 100 µg (1 mL) dexmedetomidine; and group BF (n = 15) received an intraarticular injection of 20 mL bupivacaine 0.25% plus 50 µg (1 mL) fentanyl. RESULTS: The BF group had a statistically significant longest duration of analgesia (693.3 ± 22.6 minutes) compared to group the BD (505.8 ± 23.5 minutes) and group B (244.1 ± 17.5 minutes) (P < 0.0001). The total meperidine consumption was statistically significantly decreased in group BF (35 ± 12.6 mg) compared to the BD and B groups (60 ± 12.6 mg and 83.3 ± 15.4 mg respectively) (P < 0.0001). Groups BF and BD showed a highly statistically significant lower postoperative static and dynamic pain scores at 30 minutes, 1, 2, 4, and 6 hours compared to group B. However, group BF was comparable to group BD at the same time intervals. Postoperative static and dynamic pain scores showed a highly statistically significant higher values at 4 hours in group B, 8 hours in group BD, and 12 hours in group BF (P < 0.0001). No significant side effects were observed in the groups. The duration of analgesia was the most important parameter that determined patient satisfaction. LIMITATIONS: Small sample size and lack of studies that compare both adjuvants. CONCLUSIONS: Fifty µg of fentanyl as an adjuvant to intraarticular bupivacaine produces effective and safe analgesia after knee arthroscopy as 100 µg of dexmedetomidine and has a longer analgesia duration in the first postoperative 24 hours.

Prevalence and Prognostic Implications of PD-L1 Expression in Soft Tissue Sarcomas.

Background: PD-L1 expression differs from 19 to 92% in various cancer subtypes. Its expression carries a worse prognostic value in various malignancies and could also be used as a predictive marker for immune checkpoint inhibitor response. This study aimed to explore the prevalence of PD-L1 expression in soft tissue sarcomas and the correlation of PD-L1 expression with clinicopathological features. Patients and Methods: The tissue samples of 50 patients with STS were tested for PD-L1 expression using immunohistochemistry (IHC). We followed a 6-step proportional scoring system. The patients were treated at Ain Shams University Hospital from 2011 to 2017. We also explored the correlation of PD-L1 expression with different clinical features of the patients. The chi-square test was used to calculate the differences among variables. Results: Twelve cases (24%) showed positive PD-L1 expression with the highest prevalence in rhabdomyosarcoma and desmoid tumors (2/2 and 2/3 cases, respectively), followed by GIST in 2/4 cases and liposarcoma in 3/11 cases. Patients with positive PD-L1 expression showed a trend for worse survival, with a median overall survival of 11 months vs. 19 months for patients with negative PD-L1 expression (p-value = 0.1) and a mean PFS of 6 months vs. 11 months for patients with negative PD-L1 expression (p-value = 0.1). However, these findings did not reach statistical significance. Conclusion: Although the results did not reach statistical significance due to the small number of cases, PD-L1 expression could represent a prognostic factor for poor outcome. Larger clinical trials are recommended for the validation of PD-L1 as a poor prognostic biomarker.

Quality of Life in Patients With Hypoparathyroidism After Treatment for Thyroid Cancer.

PURPOSE: Surgical complications such as hypoparathyroidism (HPT) or vocal cord palsy are seldom assessed when the quality of life (QOL) in thyroid cancer patients is investigated. The aim of this study was to measure the QOL difference in thyroid cancer survivors with and without HPT. METHODS: Participants for this analysis were enrolled in 13 countries from a study that pilot-tested a thyroid cancer-specific QOL instrument. They were included if they had been diagnosed with thyroid cancer at least 9 months previously. QOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) and some items on HPT symptoms (eg, tingling in fingers or toes). HPT status and other clinical data were extracted from the patients' medical charts. Comparisons of QOL domains between patients with and without HPT were performed using Mann-Whitney U test. The occurrence of HPT-related symptoms was compared using chi-square tests. Multiple ordinal regression analysis was performed to evaluate factors that might affect QOL. RESULTS: Eighty-nine patients participated in this study, 17 of whom were considered to have HPT. Patients in the HPT group reported significantly reduced QOL in 9 of the 15 scales of the EORTC QLQ-C30 compared to patients without HPT. Regression analysis showed that HPT was independently negatively associated with various scales of the QLQ-C30. Both groups showed a high prevalence of typical HPT symptoms. CONCLUSION: Thyroid cancer patients with HPT report significantly impaired QOL compared to thyroid cancer survivors without HPT. The assessment of HPT should be considered when measuring QOL in thyroid cancer patients.

Nalbuphine versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section.

BACKGROUND AND PURPOSE: Adding adjuvants to intrathecal hyperbaric bupivacaine provides long analgesic duration with less adverse effects. The aim of this study was to compare intrathecal nalbuphine versus midazolam in patients undergoing cesarean section. CLINICAL TRIAL ID: NCT03918187. PATIENTS AND METHODS: This was a prospective randomized controlled study conducted on 90 females undergoing cesarean section under spinal anesthesia who were randomly allocated to three equal groups of 30 patients each: group C received hyperbaric bupivacaine 12.5 mg plus 0.5 mL saline, group N received hyperbaric bupivacaine 12.5 mg plus 1 mg nalbuphine, group M received hyperbaric bupivacaine 12.5 mg plus 2.5 mg midazolam. The onset and duration of sensory and motor block, effective analgesic time, analgesic requirements, adverse effects, sedation, and Apgar scores were recorded. RESULTS: There was significant rapid onset of sensory and motor block (1.95±.44 and 3.50±0.43 min) with slower regression of sensory block and time to bromage I (211.6±13.2 and 219.8±20.2 min) in group N compared to groups M, C (p < 0.001), with statistically significant rapid onset and long duration of both blocks in group M compared to C (p<0.001). The effective analgesic time was significantly prolonged in group N (263.7±16.3) compared to groups M and C (224.2 ± 18.6, 185.5±17.45), respectively, (p<0.001) and prolonged in group M compared to C (p<0.001), with increase in analgesic requirement in group C compared to groups N and M (p<0.001) and no significant difference between groups N and M. There was higher sedation score in groups N, M (1.78±0.63, 2.75±0.54), respectively, compared to group C (0.61±0.12) (p<0.001) with lower Apgar score in group M (6.9±0.73) at one minute than in groups N, C (7.1±0.91, 7.7±0.84) (p<0.001). There was no significant difference between groups regarding the adverse effects. CONCLUSION: Adding 1 mg nalbuphine to 12.5 mg hyperbaric bupivacaine provided more effective postoperative analgesia than adding 2.5 mg midazolam, with less non-significant adverse effects in midazolam group in patients undergoing elective cesarean section.

Improved chemo-photothermal therapy of hepatocellular carcinoma using chitosan-coated gold nanoparticles.

A green method was used for producing gold nanoparticles (Au NPs) using chitosan as a natural cationic, biodegradable and biocompatible polymer. In this method, chitosan acts as a reducing and stabilizing agent for the synthesis of Au NPs. Different concentrations of chitosan solutions (0.01%, 0.05%, 0.1%, 0.2%, 0.5% and 1%) were applied. In an attempt to mitigate the side effects of anti-cancer drug, 5-fluorouracil (5-FU), through reducing drug doses in photothermal therapy, the formed positively-charged chitosan-wrapped Au NPs were used as a drug delivery system for negatively charged 5-FU to hepatocellular carcinoma cells (HepG2). Au NPs as well as 5-FU@Au nanocomposites were characterized with UV-VIS spectroscopy, particle size, zeta potential, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and High-Performance Liquid Chromatography (HPLC). The chitosan concentration was shown to be an important parameter for optimizing the dispersion of Au NPs and 5-FU@Au nanocomposites over long time. This stability offers the 5-FU@Au nanocomposites as good candidate for cancer treatment with reduced drug doses in photothermal therapy. A 72% loading-efficiency of 5-FU was obtained. Cytotoxic assay was carried out on HepG2 cell line and it reveals the effectiveness of 5-FU@Au nanocomposites in the presence and absence of laser irradiation compared with the free 5-FU. The cytotoxicity effect of free 5-FU and 5-FU@AuNPs nanocomposites was studied, and it was found that the concentration of 5-FU@Au nanocomposites required to attain 50% of inhibition growth rate was lower than that of free 5-FU in absence of laser radiation and was much lower in presence of laser radiation.

The EORTC module for quality of life in patients with thyroid cancer: phase III.

The purpose of the study was to pilot-test a questionnaire measuring health-related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire, and whether they found the items understandable, confusing or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not confusing, few missing values, neither floor nor ceiling effects, and high variance. A total of 182 thyroid cancer patients in 15 countries participated (n = 115 with papillary, n = 31 with follicular, n = 22 with medullary, n = 6 with anaplastic, and n = 8 with other types of thyroid cancer). Sixty-six percent of the patients needed 15 min or less to complete the questionnaire. Of the 47 items, 31 fulfilled the predefined criteria and were kept unchanged, 14 were removed, and 2 were changed. Shoulder dysfunction was mentioned by 5 patients as missing and an item covering this issue was added. To conclude, the EORTC quality of life module for thyroid cancer (EORTC QLQ-THY34) is ready for the final validation phase IV.

Do cancer cells in human and meristematic cells in plant exhibit similar responses toward plant extracts with cytotoxic activities?

We examined the effect of water extracts of Persea americana fruit, and of the leaves of Tabernamontana divericata, Nerium oleander and Annona cherimolia (positive control) on Vicia faba root cells. We had confirmed in our previously published data the cytotoxicity of these plant extracts on four human cancer cell lines: liver (HepG-2), lung (A549), colon (HT-29) and breast (MCF-7). Vicia faba roots were soaked in plant extracts at dilutions of 100, 1,250, 2,500, 5,000, 10,000, 20,000 ppm for 4 and 24 h. All treatments resulted in a significant reduction in the mitotic index in a dose dependant manner. Root cells treated with T. divericata, N. oleander and A. cherimolia exhibited a decrease in prophase cell percentage, increase in micronuclei and chromosomal abnormalities as concentration increased. The P. americana treatment showed the highest cytotoxic effect on cancer cells, prophase cell percentage increased linearly with the applied concentration and no micronuclei were detected. This study shows that root tip assay of beans can be used in initial screening for new plant extracts to validate their use as candidates for containing active cytotoxic agents against malignant cells. This will greatly help in exploring new plant extracts as drugs for cancer treatment.

Phase II trial of metronomic chemotherapy as salvage therapy for patients with metastatic breast cancer.

AIM OF WORK: To evaluate the efficacy and tolerability of metronomic chemotherapy (which is the continuous administration of chemotherapy at relatively low minimally toxic doses on a frequent schedule of administration at close regular intervals with no prolonged drug-free breaks) in metastatic breast cancer patients as salvage therapy. PATIENTS AND METHODS: In this phase II study we evaluated the clinical efficacy and tolerability of low dose, oral Methotrexate (MTX) and Cyclophosphamide (CTX) in patients with metastatic breast cancer. Between January 2004 and December 2005, 42 patients received MTX 2.5mg bid on day 1 and 2 each week and CTX 50mg/day administered continuously. RESULTS: Forty two patients were evaluable. The overall clinical benefit was 31% complete response, partial response and stable disease (CR+PR+SD >or=24 weeks), while the overall response rate was 16.7% (none of the patients attained CR). Toxicity was generally mild. The most common non hematological toxicity was elevation in transaminases level, it was reported in 40.4% of patients and was reversible, while mild grade 1 or 2 neutropenia was the most common hematological toxicity, (28.5% of patients). Median time to response was 3+/-0.18 while progression free survival (PFS) among patients with clinical benefit was 10 months (95% CI 6.65-13.44). CONCLUSIONS: This phase II study shows that, the combination of continuously low dose MTX and CTX is an active minimally toxic and significantly cost effective regimen for the treatment of metastatic breast cancer patients.

Assessment of Survival and Clinical Benefit in Malignant Pleural Mesothelioma (MPM) Patients Treated with Gemcitabine and Carboplatin.

PURPOSE: To evaluate the efficacy, safety, and clinical benefit of combined gemcitabine and carboplatin in patients with previously untreated malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: This prospective phase II study was performed on 42 eligible patients with histologically or cytologically proven MPM presenting to Ain Shams University hospitals and Sohag Cancer Center between January 2002 and April 2006. They were assigned to receive combined gemcitabine (1250mg/m2) on days, 1 and 8 and carboplatin (AUC 6) on day 1. The regimen was repeated every 21 days. The treatment continued until disease progression or intolerable drug toxicity. RESULTS: The patients received a total of 227 cycles of chemotherapy (median 5.4 cycles and range from 2 to 9 cycles). The chemotherapy was generally well tolerated. Neutropenia, thrombocytopenia and anemia were the most severe (Grade 3 or 4) toxicities recorded during therapy and were reported in (14%), (9.5%), and (9.5%), respectively. Twelve patients (29%) achieved partial response, 18 patients (42%) had stable disease and the disease progressed in the remaining 12 patients (29%). The median follow-up duration was 11 months (range 5 from 20 months). The overall survival (OS) and progression free survival (PFS) at one year was 44.5% and 33.2%, respectively. The median survival and time to disease progression were 11 months and 8.5 months respectively. Of 32 patients assessed for clinical benefit, 20 patients (62.5%) were considered clinical benefit responders. CONCLUSION: The combination of gemcitabine and carboplatin is a safe and tolerable treatment with reasonable response rate, OS, and PFS compared with the historical phase II single agents and combined chemotherapy studies in patients with MPM. Key Words: Mesothelioma , Gemcitbine , Carboplatin.