Colorectal cancer in young patients: characteristics and outcome

Colorectal cancer is predominantly a disease of the elderly population, but this disease is unusual in patients 40 years of age or under, and controversy persists as to prognosis in this subset of patients. The aim of this study was to determine the clinicopathologic features and their impact on patients survival of colorectal cancer in patients aged 40 years or younger, and to compare them with those of older patients. The records of 466 patients with non-metastatic colorectal adenocarcinoma who were referred between 1991 and 1999 to the University of Istanbul, Institute of Oncology, following curative surgery were retrospectively analysed. The clinicopathologic features of 84 (18%) colorectal cancers (group A; male:female ratio 48:36) which occurred in patients aged 40 years or younger were compared with 382 colorectal cancers in older patients (group B; male:female ratio 194:188). Patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, lymphatic invasion, serum levels of LDH and CEA, and survival rates were compared as prognostic factors. There was no statistically significant difference between group A and group B with respect to patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, serum levels of LDH and CEA, and survival rates of colorectal cancers. The proportion of lymphatic invasion was present in 27% of patients in group A vs. 12% in group B. With median follow-up of 69 months, the overall 5-year survival rate was 61% in group A and 56% in group B. In the univariate survival analysis according to age groups (group A and B), advanced TNM stage, location of rectal tumor, presence of lymphatic invasion, and presence of high serum LDH and CEA levels are predictors of poorer survival in young patients with colorectal cancer. In the Cox-Regression analysis, location of tumor and TNM stage were determined as independent prognostic factors for survival. This study revealed no difference in clinicopathologic characteristics in patients with colorectal cancer aged 40 years or younger compared with those aged above 40 years. However, in patients aged 40 years or younger, distal location of tumor and advanced stage should be considered as poor prognostic factors for overall survival.     

Postoperative atrial fibrillation in patients with left atrial myxoma

Paroxysmal atrial fibrillation (AF) is the most common arrhythmia following cardiac surgery such as coronary artery bypass grafting (CABG), and often occurs between the second and fourth postoperative days.1,2 The reported incidence of paroxysmal AF after CABG surgery varies widely, from five to 40%, which is lower than in cases of valvular cardiac surgery.3,4 Although this arrhythmia is usually benign and self-limiting, it may also be associated with increased risk of embolic events, haemodynamic instability, haemorrhagic complications, prolonged hospital stay and higher rates of re-admissions, increasing the healthcare costs.5-7Several risk factors have been proposed for paroxysmal AF after CABG or valvular cardiac surgery, such as advanced age, genetic predisposition, chronic obstructive pulmonary disease, heart failure or increased peri-operative ischaemia.8-10 In addition, certain echocardiographic parameters such as left atrial (LA) diameter or left ventricular (LV) function, and electrocardiographic parameters including P-wave duration and P-wave dispersion (Pd) have been shown to be associated with postoperative AF.11-13Although postoperative AF and its predictors after CABG and valvular surgery have been well researched, no study has been performed to explore the incidence or predictors of postoperative AF in patients with LA myxoma. The aim of this study was to identify the prevalence and predictors of postoperative AF in a pure cohort of patients with LA myxoma.     

Prognostic factors in patients with aggressive non-Hodgkin’s lymphoma without complete response to first-line therapy

This study was conducted to retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin’s lymphoma who did not achieve a complete response (CR) to first-line therapy. Prognostic factors in terms of survival were analyzed in 76 adult patients with non-Hodgkin’s lymphoma who had failed to achieve CR to first-line chemotherapy (CT) regimens administered at Istanbul University, Institute of Oncology, between February 1989 and October 1998. A total of 41 patients were female, and median age was 60 y (range, 18–87 y). Twenty-seven patients (35%) had primary refractory disease (stable disease + progressive disease). A partial response (PR) was demonstrated in 49 (65%). In all, 92% had been administered anthracycline on the basis of computed tomography findings. Of 27 patients with primary refractory disease, 20 died because of initial CT toxicity or disease progression. A total of 10 patients with primary refractory disease underwent second-line CT. CR was observed in only 1 of those patients. Of the 49 patients who had a PR to first-line therapy, 31 died because of disease progression. Of those patients, 14 underwent second-line CT. Four patients were observed to have a CR. Median overall survival (OS) in all patients was established at 15 mo (range, 11–19 mo), and 5-y OS was 25%. On the other hand, median OS in patients with primary refractory disease was 7.6 mo (range, 5.7–9.4 mo) and was observed to be 17.8 mo (range, 9.4–26.1 mo) in patients with a PR. The difference in survival rates between patients with primary refractory disease and those with a PR was significant (P=.005). Although median OS was 18.1 mo (range, 8.4–27.8 mo) in patients with intermediategrade histology, it was 6.1 mo (range, 1–11.7 mo) in patients with high-grade histology (P=.001). As a result of univariate analysis, significant prognostic factors associated with OS included histologic grade (intermediate/high) (P=.001), response to initial therapy (primary refractory disease/PR) (P=.005), performance status (0–2/2–4) (P=.024), and International Prognostic Index risk groups (low/low intermediate/intermediate-high/high risk) (P=.004). Multivariate analysis revealed that independent prognostic parameters associated with OS included response to initial therapy (P=.009) and histologic grade (P=.001). Although prognosis is rather poor in patients with high histologic grade and primary refractory disease, patients with a PR have a slightly better prognosis.     

Proteasome inhibitors and IMiDs can overcome some high‐risk cytogenetics in multiple myeloma but not gain 1q21

Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population‐based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow‐up of patients still alive at analysis was 40 months for the high‐dose (HDT)‐treated ones and 29 months for the whole population. Three hundred forty‐seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3‐yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO P < 0.001; gain 1q21 vs. OA P = 0.095). If treated with PI or IMiDs, the 3‐yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P = 0.041, P = 0.140). In HDT patients, the 3‐yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (P < 0.008, P = 0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.     

Effect of Seven Different Modalities of Antihypertensive Therapy on Pulse Pressure in Patients with Newly Diagnosed Stage I Hypertension

In this study, we investigated the effect of different antihypertensive agents on pulse pressure (PP). The study was designed in a prospective manner and patients were sequentially allocated to one of the seven different therapy groups, according to the order of enrollment (every first patient to group I, every second patient to group II, and etc). Patients in group I received 10 mg of lisinopril, in group II 10/6.25 mg of lisinopril/hydrochlorothiazide, in group III 80 mg of valsartan, in group IV 80/6.25 mg of valsartan/hydrochlorothiazide, in group V 5 mg of amlodipine, in group VI 1.25 mg of indapamide, and finally those in group VII received 50 mg of atenolol. The reduction in PP was more significant in patients receiving lisinopril, lisinopril hydrochlorothiazide, valsartan, and valsartan hydrochlorothiazide, when compared with patients receiving indapamide, atenolol, and amlodipine (P < 0.05 for each group). Factors such as age, gender, and body mass index were not found to significantly influence the effectiveness of antihypertensive agents on PP. The reduction in PP was more apparent with lisinopril, lisinopril hydrochlorothiazide, valsartan, and valsartan hydrochlorothiazide in diabetic patients, when compared with those without diabetes (P < 0.001, P < 0.05). And also patients on therapy with 3‐hydroxy‐3‐methyl‐glutaryl‐CoA (HMG‐CoA) reductase inhibitors had a greater reduction in PP with lisinopril, lisinopril hydrochlorothiazide, valsartan, and valsartan hydrochlorothiazide (P < 0.001, P < 0.05).     

Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components

Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)-compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.     

Treatment of cubitus varus using the Ilizarov technique of distraction osteogenesis

Seven children with a post-traumatic cubitus varus deformity were treated using the Ilizarov technique of distraction osteogenesis. The outcome was rated as excellent in each case and all were satisfied with the cosmetic appearance. No complications had been encountered by the latest follow-up at a mean of 66.7 months. This technique seems reliable for the treatment of such deformities, provided that it achieves full correction by gradual distraction. Nerve palsy and unsightly scars are avoided, and the range of movement of adjacent joints is preserved.