Signet ring cell carcinoma metastasis in the bone marrow accompanied by cancer related thrombotic microangiopathy as a first presentation.

Cancer related thrombotic microangiopathies usually cause a diagnostic dilemma for hematologists and clinicians. In this case report, we presented a fifty-nine-year-old man who was admitted to our hospital with microangiopathic hemolytic anemia and thrombocytopenia due to the carcinoma metastasis to the bone marrow. As a result of rapid evaluations, it was revealed that the histological subtype of the cancer was signet ring cell carcinoma, and despite all the interventions, the patient died at a very short time after the initial presentation. Regardless of all the innovations in the diagnosis and treatment of thrombotic microangiopathies, cancer-associated thrombotic microangiopathy is still fatal and deadly today.

Factors affecting prognosis and treatment strategies in metastatic soft tissue sarcomas: twenty years of experience.

OBJECTIVE: In this study, we aimed to reveal the general clinicopathological features, treatment features, and factors that could predict overall survival in metastatic soft tissue sarcomas, a very rare and heterogeneous disease group. PATIENTS AND METHODS: This study was a retrospective cohort study. Patients monitored with metastatic soft tissue sarcoma between January 2001 and January 2021 were evaluated retrospectively. Patients aged 18 years and over, histopathologically diagnosed with metastatic STS, and unsuitable for operations, such as local curative surgery or metastasectomy, were included in the study. RESULTS: A total of 179 patients in the metastatic stage and monitored in our center were included in the study. The median follow-up period was 8.4 months (IQR, 3.4-14.4). 58 (32.4%) patients were de-novo metastatic, and 121 (67.6%) patients developed metastasis later. The median age was 53.2 (Range: 18.8-87.6 years), and 101 (56.4%) patients were male. The most common primary location was the lower extremity (87) (48.6%). The most common histological subtypes were synovial sarcoma (38) (21.2%), pleomorphic sarcoma (37) (20.7%), and liposarcoma (26) (14.5%). The majority were grade 3 tumors (n=131, 73.2%). Having ECOG PS 2-3 (HR=2.829, 95% CI 1,667-4.800, p<0.001), having tumor grade as 3 (HR=1.748, 95% CI 1.150-2.656, p<0.009), receiving palliative chemotherapy (HR=0.294, 95% CI 0.144-0.600, p<0.001), and receiving two or more lines of chemotherapy among those palliative receivers (HR=2.505 95% CI 1.696-3.700, p<0.001) were independent predictive factors of mortality. CONCLUSIONS: Survival in metastatic soft tissue sarcoma is better in patients with good ECOG performance status, low tumor grades, and who have received palliative chemotherapy. Receiving more than one line of palliative systemic treatment for progressive disease improves survival.

The inmunohistochemical expression of c-Met is an independent predictor of survival in patients with lioblastoma multiforme

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care (AU)

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The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

Gemcitabine and cisplatin combination chemotherapy in triple negative metastatic breast cancer previously treated with a taxane/anthracycline chemotherapy; multicenter experience.

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.

Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure.

PURPOSE: To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients. METHODS: All patients in this study had previously failed oxaliplatin and irinotecan-based chemotherapy. Patients were treated with MMC (6 mg/m(2) intravenously/i.v.) on day 1 in combination with either oral UFT (500 mg/m(2)) and oral leucovorin (LV) (30 mg) on days 1-14 every 3 weeks (group A) or infusional 5-fluorouracil (5-FU) by deGramont regimen with i.v. LV (200 mg/m(2)) on days 1 and 2, every 2 weeks (group B). RESULTS: Thirty-nine MCRC patients were analyzed. Twenty-two of them were in group A and 17 in group B. Thirty-three were evaluable for clinical efficacy. The clinical benefit in the intent-to-treat (ITT) population was 30.8%. Median progression free survival (PFS) was 6 months (95% confidence interval/ CI 4-8) and median overall survival (OS) 9 months (95% CI 6.5-11.5). Median PFS was 3 months (95% CI 2.4-3.6) in group A and 7 months (95% CI 5.1-8.9) in group B (p=0.009). Median OS was 7 months (95% CI 4.3-9.7) in group A and 12 months (95% CI 5.4-18.6) in group B (p=0.422). The combination of MMC and fluoropyrimidines was generally well tolerated. The most common severe toxicities were nausea and vomiting, neutropenia, hepatotoxicity and diarrhea. CONCLUSION: MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients. This combination remains a viable option in these patients. However, better therapies are urgently needed.

Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.

Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver, lung and gynecological malignancies as synchronous or metachronous cancer. However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a 72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass lesions far away from the primary tumor in cancer patients can be not only the sign of distant metastasis but also another primary malignancy. In the English literature, synchronous gastric adenocarcinoma and HL has been rarely reported, and as far as we know, this is the third case to be reported.

Acute arsenic self-poisoning for suicidal purpose in a dentist: a case report.

Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

Blood viscosity in patients with diffuse large B cell non-Hodgkin's lymphoma.

UNLABELLED: The aim of the study was to evaluate blood viscosity as possible marker of disease progression in patients with newly diagnosed non-Hodgkin's lymphoma (NHL). METHODS: The viscosity of blood samples from 20 patients with newly diagnosed aggressive NHL (stage I, n=7; stage II, n=4; stage III, n=7; stage IV, n=2) was analyzed using Brookfield DV-II + (USA) machine. RESULTS: Blood viscosity in NHL patients (median: 5.5+/-1.46 miliPascal) inversely correlated with lactatdehydrogenase (LDH) level, international prognostic index (IPI) score, and stage (p=0.02, r=-0.51; p=0.03, r=-0.63; and p=0.04, r=-0.45, respectively) and positively correlated with hemoglobin level (p=0.02, r=0.65)). CONCLUSION: According to our data, blood viscosity may be considered as a follow up marker in NHL patients along with LDH level or sedimentation rate.

Comparison of bupivacaine 0.2% and ropivacaine 0.2% combined with fentanyl for epidural analgesia during labour.

BACKGROUND AND OBJECTIVE: Recent clinical studies comparing ropivacaine 0.25% with bupivacaine 0.25% reported not only comparable analgesia, but also comparable motor block for epidural analgesia during labour. An opioid can be combined with local anaesthetic to reduce the incidence of side-effects and to improve analgesia for the relief of labour pain. The purpose of the study was to evaluate the effects of epidural bupivacaine 0.2% compared with ropivacaine 0.2% combined with fentanyl for the initiation and maintenance of analgesia during labour and delivery. METHODS: Sixty labouring nulliparous women were randomly allocated to receive either bupivacaine 0.2% with fentanyl 2 microg mL(-1) (B/F), or ropivacaine 0.2% with fentanyl 2 microg mL(-1) (R/F). For the initiation of epidural analgesia, 8 mL of the study solution was administered. Supplemental analgesia was obtained with 4 mL of the study solution according to parturients' needs when their pain was > or = 4 on a visual analogue scale. Analgesia, hourly local anaesthetic use, motor block, patient satisfaction and side-effects between groups were evaluated during labour and at delivery. RESULTS: Sixty patients were enrolled and 53 completed the study. No differences in verbal pain scores, hourly local anaesthetic use or patient satisfaction between groups were observed. However, motor block was observed in 10 patients in the B/F group whereas only two patients had motor block in the R/F group (P < 0.05). The incidence of instrumental delivery was also higher in the B/F group than in the R/F group (P < 0.05). CONCLUSIONS: The results suggest that epidural bupivacaine 0.2% and ropivacaine 0.2% combined with fentanyl produced equivalent analgesia for pain relief during labour and delivery. It is concluded that ropivacaine 0.2% combined with fentanyl 2 microg mL(-1) provided effective analgesia with significantly less motor block and need for an instrumental delivery than a bupivacaine/fentanyl combination at the same concentrations during labour and delivery.

Comparison of granisetron, ondansetron and tropisetron for control of vomiting and nausea induced by cisplatin.

Severe nausea and vomiting are common and one of the most feared side effects of cisplatin-based chemotherapy. A total of 106 patients were randomized to receive a single dose of 8 mg ondansetron or 3 mg granisetron or 5 mg tropisetron intravenously as prevention of cisplatin-induced acute nausea and vomiting. Antiemetic therapy was done within 30 minutes before initiating chemotherapy. A questionnaire evaluating nausea, vomiting and retches was administered to patients and the responses were categorized as complete, partial or failure. The response determination was repeated in the first 24 hours, and within 24-72 hours following cisplatin administration. The complete response rates for ondansetron, granisetron and tropisetron in the first 24 hours were 51.4%, 65.7% and 61.1% respectively. All three agents were highly effective against cisplatin-induced acute and late vomiting and the results were statistically significant. This study demonstrated no significant difference in effectiveness of these three antiemetics. 5-HT3 (5-hydroxytryptamine 3) receptor antagonists have similar efficacy in the prevention of nausea and vomiting due to cisplatin. Thus, we recommend that drug choice be based on cost-benefit and patient tolerance.

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors.

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.

High-dose ifosfamide by infusion with Mesna in advanced refractory sarcomas.

Twenty patients with advanced sarcomas entered a pilot study with ifosfamide (IF) and mercaptoethane sulfonate sodium (Mesna) as a second-line treatment for six planned cycles. All patients had received prior doxorubicin- and cyclophosphamide-based chemotherapies. IF was administered at a dose of 3 g/m2 given as continuous intravenous infusion for 24 hr on day 1-5 with Mesna. In the absence of disease progression, chemotherapy was planned to be repeated every 4 weeks for six consecutive cycles. Following chemotherapy, only 2 patients (11%) achieved partial response with response durations of 6 and 9 months. There was no complete response. When considered for only high-grade tumors, the response rate reached up to 22%. Toxicity was reported for 48 cycles and the dose-limiting toxicities were myelosuppression (22%) and encephalopathy (17%). Chemotherapy protocol was changed after two or three courses in 16 patients with stable or progressive disease. IF/Mesna chemotherapy at this dose and schedule was not found to be very promising in refractory sarcomas as a second-line chemotherapy.