Pembrolizumab Plus Chemotherapy for Advanced and Recurrent Cervical Cancer: Final Analysis According to Bevacizumab Use in the Randomized KEYNOTE-826 Study.

BACKGROUND: In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. PATIENTS AND METHODS: Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model. RESULTS: 617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43-0.73]) and all-comer (0.57 [0.45-0.73]) populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44-0.85]) and all-comer (0.69 [0.50-0.94]) populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. CONCLUSION: Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

Is docetaxel-free interval a predictive factor for castration-resistant prostate cancer?

OBJECTIVE: Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies. MATERIAL AND METHODS: This clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients' progression time after Dx therapy and the effects on sequential treatment. RESULTS: After Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (p<0.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months. CONCLUSIONS: Our findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study.

BACKGROUND: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented. PATIENTS AND METHODS: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed. RESULTS: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'. CONCLUSIONS: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.

Protective Effects of Caffeic Acid Phenethyl Ester on Isoniazid and Rifampicin-induced Hepatic and Pancreatic Injury

ABSTRACT Objective: To investigate the protective effects of caffeic acid phenethyl ester (CAPE) against isoniazid (INH)- and rifampicin (RFP)-induced hepatic and pancreatic damage. Methods: Eighty adult rats were randomly divided into eight groups: control, INH, RFP, INH+RFP, INH+CAPE, RFP+CAPE, INH+RFP+CAPE, and CAPE. Both INH and RFP were orally administered for 30 days at a dose of 50 mg/kg/day. Caffeic acid phenethyl ester was intraperitoneally injected for 30 days (10 μmol/kg). Blood samples, hepatic and pancreatic tissues were obtained on day 30. Results: Total oxidant status levels were significantly higher in INH and/or RFP-treated groups than those of control and CAPE groups, while total antioxidant status and paraoxonase levels were significantly reduced in INH-RFP groups compared with the group receiving CAPE. Histopathological deterioration was observed in RFP and INH groups in pancreatic and hepatic tissue. However, significant amelioration was observed in CAPE-treated groups. Conclusion: Our findings suggest that CAPE may be a promising agent to prevent the side effects of INH and RFP treatment on hepatic and pancreatic tissues.

Preliminary results with non-centrifuged autologous fat graft and percutaneous aponeurotomy for treating Dupuytren's disease.

The aim of this study was to describe our experience with treating Dupuytren's disease using needle aponeurotomy and non-centrifuged autologous fat grafting. The study included 17 patients (18 hands). Patients were treated with needle aponeurotomy and non-centrifuged autologous fat graft under general anesthesia. The fat grafts were injected into the surgical area so as to stay in contact with the operated site. An extension splint was used for 1 week postoperatively and the patients received hand therapy for 3 weeks. Before the treatment, the contracture in the proximal interphalangeal and metacarpophalangeal joints was a mean of 45.06 ± 13.44 degrees and 36.56 ± 13.09 degrees, respectively. It was 1.61 ± 1.65 and -0.56 ± 3.78 degrees at 3 months, respectively. The difference between these measurements was statistically significant. The mean follow-up period was 12 months. The results were satisfactory and no complications were observed during the follow-up period. Based on the results of the study, percutaneous aponeurotomy with non-centrifuged autologous fat grafting was found to have significantly beneficial effects in the treatment of Dupuytren's disease.

The protective effects of pomegranate on liver and remote organs caused by experimental obstructive jaundice model.

OBJECTIVE: We aimed to investigate the protective potential of pomegranate extract on the liver and remote organs in rats with obstructive jaundice. MATERIALS AND METHODS: The rats were split into 4 groups. In Group 1 (G1) (sham group) rats, the common bile duct was mobilized without any ligation. Group 2 (G2) received a combination of the sham operation and synchronous treatment with pomegranate. Group 3 (G3) received common bile duct ligation (CBDL). Group 4 (G4) were subjected to CBDL and treatment with pomegranate. After 8 days, we measured total oxidative status (TOS) and antioxidant capacity in the rats' liver tissue and remote organs, and evaluated blood levels of malondialdehyde and total antioxidant capacity (TAC). RESULTS: G3 rats showed significantly raised malondialdehyde level as compared to G1 rats (p < 0.001). Following the pomegranate therapy, a decrease in malondialdehyde was observed (p = 0.015). TAC levels were significantly raised in the G3 rats compared to the G1 rats (p = 0.004). TAC levels dropped after pomegranate therapy (p = 0.011). CBDL caused elevated TOS levels in the liver and remote organs, with a statistically significant increase in the lung tissue (p = 0.002). TOS levels in the CBDL groups decreased after pomegranate treatment (p < 0.001). CONCLUSIONS: This study reveals the marked protective effect of pomegranate on the liver and remote organs in obstructive jaundice.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients.

AIM: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. MATERIALS AND METHODS: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m(2) twice daily on days 1-14 of the same 21-day schedule. RESULTS: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand-foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. CONCLUSIONS: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

Effect of Intraperitoneal Thymoquinone on Postoperative Peritoneal Adhesions.

BACKGROUND: To determine the effect of thymoquinone on adhesion formation in a rat caecotomy/suture model. MATERIAL AND METHODS: Thirty wistar rats were randomized into three groups: The control group received saline and the thymoquinone group received 10 mg/kg thymoquinone after cecal caecotomy/suture model. In the sham group the abdominal wall was closed without any abrasion to the cecum. On day 15, adhesions were classified, and histopathological samples were taken. RESULTS: There were no incisional hernias or wound dehiscences. In comparing adhesion scores, a significant difference was found between the thymoquinone and the control groups (p < 0.05). The grade of inflammation for the thymoquinone and the sham groups were significantly lower than that of the control group (p < 0.01 and p < 0.001, respectively). Hydroxyproline levels were significantly lower in the sham and thymoquinone groups compared to the control group (p < 0.05). CONCLUSIONS: Based on the results of this study in a rat peritoneal adhesion model, intraperitoneal administered thymoquinone has a strong anti-adhesive effect.

The protective effect of ellagic acid on lung damage caused by experimental obstructive jaundice model.

AIM: This study aimed to investigate protective effects of ellagic acid on lungs in an experimental obstructive jaundice model. METHODS: Four groups were established, each consisting of ten randomly selected rats: Group 1: sham, Group 2: ellagic acid, Group 3: obstructive jaundice, and Group 4: obstructive jaundice + ellagic acid. Ellagic acid was administered orally at a dose of 60 mg/kg/day to group 2 and 4. The animals were sacrificed eight days later. The total oxidative status and the total antioxidant capacity in their lung tissue were determined, and malondialdehyde levels in their blood were measured. Histopathological changes in the lungs were examined. RESULTS: In the obstructive jaundice group treated with ellagic acid, there was a decrease in malondialdehyde levels and a reduction in the total oxidative status and the oxidative stress index, whereas the total antioxidant capacity increased (p < 0.001). The histopathological examination showed that neutrophil leukocyte infiltration and edema formation decreased and destruction of lung parenchyma disappeared following the treatment with the ellagic acid (p < 0.05). CONCLUSION: This study shows that ellagic acid has a protective effect against oxidative damage in lung tissue in obstructive jaundice.

The effects of pomegranate on bacterial translocation in rats with obstructive jaundice.

BACKGROUND: Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased bacterial translocation. AIMS: This study aimed to evaluate potential effects of pomegranate on bacterial translocation after bile duct ligation in rats. MATERIALS AND METHODS: Wistar albino rats were randomized into four groups. Group 1 underwent sham operation; Group 2 underwent sham operation and simultaneous treatment with pomegranate; Group 3 underwent common bile duct ligation, and Group 4 underwent common bile duct ligation and simultaneous treatment with pomegranate. After 8 days, the samples of systemic blood, liver, spleen and mesenteric lymph nodes (MLNs) were obtained under sterile conditions for microbiological culture. The segments of the ileum were removed for histopathological examination. RESULTS: Bacterial translocation significantly decreased in Group 4 compared to Group 3 (p = 0.007). The bacterial counts (Colony forming unit: CFU/g) of Group 3 were significantly higher than those of Groups 1, 2 and 4 (p < 0.05). The mean ileal villus heights in the Groups 1, 2, 3 and 4 were 480.5±20.5 µm, 494.7±17.3 µm, 356.3±25.7 µm and 420.7±23.7 µm, respectively. The mean villus height in Group 4 was higher than that of Group 3 (p = 0.010). CONCLUSIONS: Pomegranate has significant protective effects on intestinal mucosa barrier in obstructive jaundice and reduces bacterial translocation.  

The effects of curcumin on the liver and remote organs after hepatic ischemia reperfusion injury formed with Pringle manoeuvre in rats.

BACKGROUND: We aimed to investigate the effects of curcumin on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. MATERIALS AND METHODS: Totally 40 rats, divided into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and curcumin application, Group III hepatic IR; and Group IV as hepatic IR and curcumin application group. Ischemia was generated by hepatoduedonal ligament clamping for 30 minutes and then reperfusion is started. Curcumin capsules were opened and appropriate dose had been created within weighing scales. After calculations, the powder was diluted with saline. Fifteen minutes before the ischemia, curcumin was applied via oral gavage. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. RESULTS: Plasma malondialdehyde levels were found to be higher (p < 0.001), but total antioxidant activity values were not different in IR group compared with IR + curcumin group (p > 0.05). Biochemical and histopathological evaluation of tissue samples revealed that there were no differences in total antioxidant activity, total oxidant activity and histopathologic scores in IR + curcumin group compared with values of IR group (p > 0.05). CONCLUSIONS: Curcumin did not reduce the effects of hepatic ischemia reperfusion injury on the liver and distant organs including kidneys and lungs significantly.

Sigmoid colon torsion: mortality and relevant risk factors.

INTRODUCTION: Sigmoid volvulus is an important acute intestinal obstruction, leading to high mortality and requiring urgent operation. The purpose of this study is to analyze risk factors for mortality in patients that were operated on due to sigmoid volvulus at our Department. MATERIALS AND METHODS: The retrospective study included 158 patients, who were operated on due to sigmoid volvulus between January 1994-December 2010, in terms of age, gender, complaints at admission, physical signs, period of symptoms before admission, associated diseases, laboratory and radiological parameters, hospital stay, morbidity, and mortality. RESULTS: The study consisted of 135 men (85.4%) and 23 women (14.6%), with a mean age of 62.54 years. Cardiovascular disease and respiratory disease were present in 34 (21.5%) and 42 (26.6%) patients, respectively. Urgent operation was undertaken in 125, while 33 received elective surgery. Abdominal distension and pain was evident in all the patients. Generalized tenderness was detected in 58.2%, while 70.9% had hyperactive bowel sound with tympanism. Plain radiograph revealed an impression of "omega ans" in all patients, while free air was detected in 11.4% of them. Risk factors for mortality included age (p = 0.008), delayed admission (p = 0.001), cardiovascular and respiratory diseases (p = 0.001), fluid-electrolyte imbalance (p =0.001), presence of necrosis (p = 0.001), and major contamination (p = 0.001). Wound infection and intraabdominal abscess were more common in patients that developed mortality (p = 0.001 and p = 0.002). CONCLUSIONS: Complications like wound infection and intraabdominal abscess are more frequent in the patients with the risk of mortality. Delayed admission results in higher risk of mortality. Mortality rates can be reduced by early admission, preoperative intensive resuscitation, suitable antibiotics, and emergent and viable surgery.  

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis.

PURPOSE: Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment. METHODS: We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers. RESULTS: Median age of group was 58. 82 % had an ECOG PS of 0-1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate. CONCLUSION: Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate.

The prevalence and significance of autoantibodies in patients with non-Hodgkin's lymphoma: are they correlated with clinicopathological features?

PURPOSE: It is well known that an association exists between the pathogenesis of lymphomas and autoimmune diseases. Autoantibodies are detected at higher frequency in lymphoproliferative diseases, but neither the precise role of the immune system nor the cause of this is comprehensively understood. In this study we evaluated the presence and significance of some autoantibodies for patients with non- Hodgkin's lymphoma (NHL). METHODS: 150 patients with NHL who had either newly diagnosed disease, or active disease being under chemotherapy or were disease-free during follow-up, were analyzed. The frequency of autoantibodies and the relationship between autoantibodies and several clinicopathological factors were evaluated. RESULTS: The majority of the patients (50%) had diffuse large B-cell lymphoma (DLBCL). Thirty-two patients (21.4%) were newly diagnosed, 81 (54%) had active disease and were receiving chemotherapy and 37 (24.6%) were disease-free and followed-up. Fifty-one patients (34%) had stage IV disease. Antinuclear antibodies (ANA) were found in 7 (4.7%) patients, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in 10 (6.7%), anti dsDNA in 1 (0.7%), anti ssDNA in 16 (10.7%), anti Jo-1 in 3 (2%), anti-scleroderma antibody (anti Scl-70) in 4 (2.7%), and rheumatoid factor (RF) in 85 (56.7%) patients. No c7horbar;ANCA positivity was found. The mean levels of anti Jo-1 (p=0.028), anti ssDNA (p=0.014), c-ANCA (p=0.015), ANA (p=0.026) and RF (p=0.046) were significantly higher in cases with DLBCL compared to patients with non-DLBCL. In addition, in patients with newly diagnosed NHL the mean levels of anti Scl- 70 (p=0.023), anti Jo-1 (p7equals;0.017), and RF (p=0.046) were significantly higher than the other patient groups. No significant correlation was detected between the presence of autoantibodies and other clinicopathological factors. CONCLUSION: Our results show that the frequency of autoantibodies is high in NHL patients, especially in DLBCL and newly diagnosed cases. Autoantibodies may be helpful for the diagnosis of autoimmune diseases, but regular and long follow-up is needed in NHL patients with high levels of autoantibodies.

Elective bladder preservation with multimodality treatment for bladder cancer.

PURPOSE: To observe the outcome of maximal transurethral resection of bladder tumor (TURBT) followed by induction chemotherapy and concurrent chemoradiotherapy in medically inoperable patients with bladder cancer. METHODS: This study included 30 patients with stage T 2-4 bladder cancer. The patients were first treated with TURBT, and then received 2 cycles of induction chemotherapy with gemcitabine and cisplatin, followed by concurrent chemoradiotherapy with gemcitabine. RESULTS: Median follow up was 28.9 months. Radiologically, complete and partial response rates were 60 and 36.7%, while cystoscopically they were 40 and 30%, respectively. Local progression (4 cases) and distant metastasis (11 cases) were noted. Median overall survival and progressionfree survival were 32 and 21 months, respectively. One -and 2-year overall survival and progression-free survival rates were 97.60% and 83.49%, respectively. CONCLUSION: The multimodal treatment performed in this study was well tolerated and achieved a high rate of bladder preservation in selected patients with bladder cancer.

The effects of ellagic acid on the liver and remote organs' oxidative stress and structure after hepatic ischemia reperfusion injury caused by pringle maneuver in rats.

INTRODUCTION: We aimed to investigate the possible protective effects of ellagic acid (EA) on the liver and remote organs against the hepatic ischemia-reperfusion injury. METHODS: Forty Wistar-Albino rats were divided into four groups each containing 10 rats. Group I with laparotomy only, Group II with laparatomy and ellagic acid application, Group III with hepatic ischemia-reperfusion and Group IV with hepatic ischemia-reperfusion and ellagic acid application. Hepatic ischemia was induced by pringle's manoeuvre for 30 minutes followed by 30 minutes reperfusion period. After induction of ischemia, EA was applied via oral gavage at a dose of 85 mg/kg. Blood samples were taken from the animals for biochemical analysis at 60th minute of the experiment in all groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical analyses and histopathological examinations. RESULTS: The administration of EA reduced serum malonyldialdehid levels (p<0.05) and liver's oxidative stress index compared with the non-use EA groups (p0.05). The use of EA did not exert significant protective effects against the effects of liver ischemia-reperfusion injury on the kidney and lung. CONCLUSION: In our experiments ellagic acid reduced the liver oxidative stress induced by ischemia-reperfusion injury. However, no significant histological improvement was found with EA. There were no significant protective effects on the remote organ injuries induced by ischemia-reperfusion (Tab. 3, Fig. 7, Ref. 37).

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Splenic injuries: factors affecting the outcome of non-operative management.

PURPOSE: The aim of this study was to evaluate the outcome of non-operative management (NOM) in patients with splenic injuries and to determine the predictive factors of NOM failure. METHODS: Two hundred and six patients with splenic injury were admitted between January 2005 and April 2011. Of the 206 patients with splenic injury, 47 patients met the inclusion criteria of NOM. The mechanism of injury, grade of splenic injury, other intra- and extra-abdominal injuries, systolic blood pressure on admission, hemoglobin levels, number of transfusions, Injury Severity Score (ISS), Glasgow Coma Scale score, and hospitalization period were recorded. The patients were divided into two groups: those with NOM and those in whom the failure of NOM led to laparotomy. The patients were monitored for vital signs, abdominal findings, and laboratory data. NOM was abandoned in cases of hemodynamic instability, ongoing bleeding, or development of peritonitis. Independent predictive factors of NOM failure were identified. The patients managed non-operatively were compared with the patients for whom NOM failed. RESULTS: NOM was successful in 40 of 47 patients. There were differences between the two groups for ISS, hemoglobin levels, need for blood transfusion, and the number of associated extra-abdominal injuries. The grade of splenic injury was determined to be an important and significant independent predictive factor for the success of NOM of splenic injuries. CONCLUSIONS: The grade of splenic injury is an important and significant independent predictor factor for the success of NOM. NOM is not recommended in patients with high-grade splenic injury.

Unusual extraperitoneal rectal injuries: a retrospective study.

PURPOSE: Rectal injuries, which are rarely encountered because of the anatomic characteristics, occur due to penetrating traumas. In the current study, we aimed to present experiences gleaned from our clinic concerning rarely encountered unusual rectal injuries, including those cases presented for the first time. METHODS: Eleven patients who had been treated for unusual rectal injuries in the General Surgery Clinic of Dicle University between 2004 and 2011 were retrospectively reviewed. RESULTS: The reasons for rectal injuries included foreign bodies in four cases, sexual intercourse in three cases, iatrogenic injuries in two cases, electric shock in one case, and animal horns in one case. All cases had extraperitoneal rectal injuries and all injuries were grade 2 injuries, except for the electrical burn. Primary repair was adequate for the treatment of six patients. Four patients underwent primary repair and ostomy, whereas one of the patients underwent debridement and an ostomy. The patients recovered without complications, except for one patient with sphincter insufficiency. CONCLUSION: The results of the current study suggested that primary repair is adequate in the patients with low-energy injuries and early presentation, whereas an ostomy is required for those with late presentation and for those with high-energy and destructive injuries.