Top PDF The outcome of surgical treatment in patients with obstructive colorectal cancer

Toplam 12 (%14) olguda mortalite görüldü. Bu olguların tamamı ağır komorbiditesi olan, ASA sko- ru 3 ve üzeri, 70 yaş üstü hastalardı. Mortalite ile sonuçlanan 12 olguya ait özellikler Tablo 2’de gö- rülmektedir. Çalışmamızda yaşın 70’in üzeri olması (p=0,021), komorbiditenin varlığı (p=0,006), albü- min değerinin 3 g/dl’nin altında olması (p=0,014), ASA skorunun 3 ve üzeri olması (p=0,003), 500 ml’den fazla kan kaybı (p<0,001), ameliyatta kan verilmesi (p=0,008) mortaliteye etkili faktörler ola- rak bulundu.

Besides cancer cells themselves, a tumor comprises stromal cells. The interactions of stromal and cancer cells is thought to be a major determinant of the tumor behavior and response to therapy [3, 4]. Cellular components of the stroma are fibroblasts, endothelial cells, immune cells and pericytes [5]. Cancer-associated fibroblasts (CAF), and especially activated fibroblasts, play a major role in the tumor-stroma network, similar to dermal fibroblasts in wound healing. This contributed to the description of tumors as “wounds that do not heal” by Dvorak et al. in the late 80’s [6]. CAF contribute to various tumor-promoting characteristics like extra-cellular matrix turnover, tumor growth, angiogenesis and metastasis [7, 8]. Due to the expression of α- smooth muscle actin (α-SMA), activated CAF are often described as myofibroblasts. They have also been shown to be positive for fibroblast-activation protein-α/seprase, palladin and vimen- tin [9–12]. Recently, efforts have been made to characterize the “signature” of these fibroblasts by proteome and gene expression profiling [13, 14].

The results of a multicentre, international (West- ern Europe, Central Europe, Eastern Europe, Cana- da, Australia, New Zealand), open-label phase III Ran- domized Controlled Trial (RCT) in which 463 patients with metastatic colorectal cancer with EGFR expres- sion were randomized to receive panitumumab (6 mg/kg per IV infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity) and “best supportive care” (BSC) [n = 231] or “bet- ter supportive care alone” [n = 232]. The study was reported in a major publication 7 (B) and five comple-

The association between miR-664-3p and OS differed signif- icantly between patients treated with bevacizumab and patients treated with chemotherapy alone: Increasing miR-664-3p expres- sion in primary CRC tissue was associated with longer OS in both cohorts of patients treated with bevacizumab combined with CAPEOX but not in the cohort treated with chemotherapy alone. Increasing miR-664-3p expression was also associated with longer TTP in patients treated with bevacizumab, but the interaction test was only significant in the subgroup of patients with sigmoid colon- and rectal primary tumors. We previously hypothesized that this subgroup of patients could be more likely to derive benefit from treatment with bevacizumab than patients with more proximal primary tumors [20]. MiR-664-3p expression was also higher in these patients than in patients with more proximal primary tumors (Figure S4 in File S1). In the small cohort of patients with available second line outcome data, high miR-664- 3p expression was also associated with a longer TTP only in patients continuing bevacizumab, supporting a connection between miR-664-3p expression and bevacizumab effectiveness.

The vast majority of advanced and metastatic cancers are still incurable despite the remarkable advances in translational and clinical research in the last decades. The introduction of molecular-targeted drugs has considerably enhanced the outcome of patients with solid tumours in advanced stages. However, not all molecularly selected patients will demonstrate clinical benefit and some of them will fail to respond to the therapy. Besides, even some patients who initially respond to targeted treatments often relapse due to the emergence of drug resistance.

Immediately after the removal of the surgical specimen were collected fragments of tissue obtained from the mucosa normal colic (at least 10 cm from the proximal margin of the lesion), and the periphery of the neoplastic lesion. After collection, the fragments were identified with the record of the patient name, date and place of where they had been collected. The fragments were placed in tubes suitable for storage in ultra-cooling and immediately stored at -80° C until the time of processing. The data, epidemiological, clinical and pathological findings were obtained from medical records. Histopathological data such as location of the tumor, macroscopic aspect of the tumor, lesion size, histological type, degree of cellular differentiation, depth of invasion in the intestinal wall, presence of lymphatic invasion or perineural, number of lymph nodes resected, number of lymph nodes involved, reason of lymph nodes involved and staging TNM were extracted from the histopathological report prepared by a single pathologist with expertise in colorectal neoplasia. The staging of tumors followed the TNM Classification according to the 6th edition proposed by the UICC (International Union of Cancer Control). All the sick were treated at the outpatient clinic of a colorectal neoplasia of Hospital Universitário São Francisco, Bragança Paulista, SP, Brazil, by the same professional.

A total of 76 GBC patients were treated with curative intent in our treatment goup at department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, between January 2003 and January 2011. Their clinical characteristics, laboratory data, treatment including surgical procedure, operative findings, tumor pathological histology, operative outcome, and length of hospital stay were obtained from the database. Fourteen clinicopatholog- ical variables (age, sex, gallstones, preoperative jaundice, operative curability, location of tumors, AJCC [International Union Against Cancer, 7th edition] [13] pT factor, lymph node metastasis, UICC stage, histologic differentiation, hepatic invasion, pathologic extrahepatic bile duct invasion, intraoperative blood loss and djuvant therapy) were selected for univariate and multivariate analysis to evaluate their influence on the outcome.

synchronous liver metastases treated with the “Reverse Approach”, nine cases of primary adenocarcinoma of the colon and 11 of the rectum (all cases of non-obstructive tumors). Patients were initially treated with two to six cycles of chemotherapy consisting of oxaliplatin, irinotecan, 5-FU and leucovorin. Response to chemotherapy was evaluated after three cycles and additional cycles were indicated if surgical resection of liver disease was not yet possible. Fourteen patients (70%) had liver disease and 60% had bilobar lesions larger than 5 cm. Staged hepatectomy was necessary for treatment of the bilobar injuries and portal embolization was carried out in cases where the expected remnant liver volume was inadequate. The primary tumor resection was planned in three to eight weeks after liver surgery or after completion of radiotherapy in the cases of rectal cancer. Sixteen patients (80%) had liver surgery with

Eighteen patients treated with oxaliplatin for colorectal cancer were prospectively assessed before and immediately following oxaliplatin infusion. Three of these patients were included in a prior study [15]. Patients received standard oxaliplatin containing treatment regimens with initial oxaliplatin doses ranging from 85–130 mg/m 2 given every 2 to 3 weeks for a total of 6–12 treatment cycles. Oxaliplatin (FOLFOX 4 regimen: 85 mg/m 2 , FOLFOX 6 regimen: 100 mg/m 2 ) was infused every 2 weeks in conjunction with leucovorin (200 mg/m 2 ) and followed by bolus 5-fluorouracil (5-FU; 400 mg/m 2 ). For the next 48 hours, a continuous infusion of 5-FU (600 mg/m 2 ) was given, followed by leucovorin (200 mg/m 2 ) and 5-FU bolus (400 mg/m 2 ) on the 2 nd day [2,16]. In patients receiving XELOX regimens, oxaliplatin (130 mg/m 2 ) was given intravenously every 3 weeks with oral capecitabine (1000 mg/m 2 ) twice daily for 2 weeks [17].

Even though some patients with mCRC present with a deteriorated PS in clinical practice, the best treatment for these patients remains unknown. In a previous retrospective study performed by our group, 27% of mCRC patients treated in a large public cancer center had ECOG PS 3-4 at the time the first-line treatment decision was made (7). Here, we present our findings of a systematic review of the litera- ture to answer the pragmatic clinical question of how to treat these patients with poor PS. Despite the relevance of this topic, only a few studies, with most being retrospective cohort studies or case series, have evaluated the treatment outcomes of mCRC patients with poor ECOG PS. However, some studies have suggested treatment-associated benefits, such as radiological and/or symptomatic improvement, prolonged OS and low risk of grade 3/4 toxicities with dose-reduced therapies.

ABSTRACT – Context - Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives - To investigate the ad- hesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods - Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the irst visit and 8-12 weeks after treatment. Results - Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically signiicant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusion - Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance.

OBJECTIVES: To develop two separate cost-effectiveness analyses, evaluating costs and outcomes of lapatinib associated to capecitabine (LAP/CAP) versus capecitabine alone (CAP) or trastuzumab associated to capecitabine (TRAST/CAP) versus capecitabine alone in the treatment of HER2 positive, metastatic breast cancer patients, previously treated with trastuzumab, under the Brazilian private health care system perspective. METHODS: In the absence of a trial comparing directly treat- ments with LAP/CAP versus TRAST/CAP, two separate studies were identified, each evaluating the efficacy of the combination treatment versus capecitabine alone. Population severity and dosage of capecitabine in the combined arm differed between trials, so an indirect comparison was not possible. Therefore, two independent cost- effectiveness analyses were developed. Only direct medical costs were considered, including medications, follow-up, disease progression and treatment of adverse events. Outcomes were expressed as time-to-progression (TTP). Maximum Prices to Con- sumer were considered for drug costs and procedure costs were obtained from pub- lished tariffs. RESULTS: In one year, the analysis comparing LAP/CAP to CAP resulted in 7.01 progression free months for LAP/CAP and 5.74 to CAP. Average costs were BRL130,908 for LAP/CAP and BRL62.960 for CAP, resulting in an ICER of BRL53,484 per additional month without progression. In the same time horizon, the analysis comparing TRAST/CAP to CAP resulted in 7.86 progression free months for TRAST/CAP and 6.64 to CAP. Average costs were BRL179.522 for TRAST/CAP and BRL70,012 for CAP, resulting in an ICER of BRL89,852 (USD64,180) per additional month without progression. (2005 PPP index 1USD 1.4BRL) CONCLUSIONS: Associating lapatinib to treatment with capecitabine leads to gains in time- to -progression of 1.27 months, with an average cost per additional month without progression of BRL53,484. In similar conditions, although evaluated in a different population, trastuzumab associated to capecitabine leads to 1.22 month gains in TTP with an average cost per additional month without progression of BRL89,852.

For establishing the genotype/phenotype correlation, the association between K ras mutational status and clinical-pathological characteristics (age, gender, tumor stage, grade, etc.) was studied. There was only a significant association of K ras mutational status to gender and metastatic state. No significant differences in the prevalence of K ras mutations were observed for patient age, gender, and tumor type. Of a total of 54 female subjects included in the study, 11 (20%) showed mutations in K ras, whereas of a total of 96 male subjects, only 9 (9%) harbored K ras mutations, which is in concordance with some recent studies (12). These mutations were found predominantly in tumors without metastasis. Only 20% of the mutant tumors had the distant metastatic stage. It has been observed that almost 37% of metastatic CRC cases have been found to harbor K ras mutations, and none of them showed a response to Cetuximab, a chemotherapy currently being used for CRC treatment (30).

Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortal- ity. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics, the development of new drugs against specific targets, including the pathway of an- giogenesis, has witnessed a remarkable increase. So, targets therapies through epidermal growth factor and its receptor and also KRAS pathways modulation acquired a main role whether in association with stan- dard chemotherapy and radiotherapy. With the current

as having interests in common though, It is a journey of discovery to learn of his true abilities, expand his view of the world around them and clarify what gives meaning life to him, current and future. In this group, people feel that they can be together deeply in meaningful ways of living (Corey, 2005 translated by Seyyed Mohammadi, 2006).Depression is one of the most common mood disorders that is associated with lack of pleasure, lack of motivation, increase or decrease of appetite and weight, sexual disorders, sleep and depression disorders. Depression is one of the most common complications of colorectal cancer, particularly can be seen due to reduced social activities and disability in these patients (Kaplan and Sadok, 2007 Translated by Rafie and Rezai, 1999).Depression is a risk factor in reducing survival in patients with colorectal cancer and an important factor in the treatment rejection by these patients. Regard to the high prevalence of depression in cancer patients, researchers knows embed sessions of psychotherapy and antidepressant medications as one of the main components of treatment of the patients and physicians has recommended to all professionals. On the other hand, from the view of Frankel Logo therapy, frustration, loss of meaning in life and undervalued feeling, condemn the person to choose the depression (Frankel, 1963).Group therapy has high efficiency in the health and medical situations because the group can be used to short therapy. Scot Sleek regard to this issue, studied studies in which the evidence was presented that in total, group therapy is effective as well as individual therapy to reform and change. And fundamental aspects of social skills especially role playing, exercises and feedback occurs strongly in group situations (Curry and Schneider, 2005). Also, logo therapy is a method that its use can help a person to find the meaning of life (Prochaska and Norcross, 2009 Translated by Seyyed Mohammadi, 2012).

Etiologically, colorectal perforations cause by enema ad- ministration can be divided into those that are iatrogenic and those that are secondary to weakness of the colorectal wall. Iat- rogenic perforations can occur as a result of forced introduction of the catheter into the anterior rectum wall, balloon hyperin- lation, or excessive hydrostatic pressure during contrast injec- tion. Perforations secondary to colorectal wall weakness occur in patients with a history of inlammatory bowel disease, acute diverticulitis, or obstructive colorectal processes, as well as in those who have recently undergone a surgical procedure, are of advanced age, or are on corticosteroid therapy, any of which make these patients more susceptible to perforation during the administration of the enema (3) . In such high-risk cases, the use

to surgery alone [6,7]. Subsequently, trial participants receiving 5-FU/leucovorin combined with oxaliplatin were found to have significantly improved progression-free survival of 9.0 months compared with 6.2 months in those receiving 5-FU/leucovorin alone (p<0.001) [8]. However, neutropenia and diarrhoea were important adverse effects noted in this trial. The need to manage toxicity is important because unintended effects may result in the patient having to receive a lower dose or shorter course of chemotherapy, with adverse consequences on the benefit/harm balance. Hence, there are potential clinical advantages from the development of predictive markers to guide clinicians in selecting individuals who are most likely to benefit (or least likely to be harmed) from a particular drug regimen. If individuals with high susceptibility for adverse effects could be identified before treatment, strategies to reduce the risk such as using alternative chemotherapy regimens (based on different agents or dose modification) and closer monitoring with greater use of supportive therapeutics, could be applied. Many studies have explored the predictive value of genotyping for beneficial response to chemotherapy and the likelihood of chemotherapy related adverse events [9-20] and heterogeneous conclusions were drawn about the association of individual markers with treatment outcomes. A recent genome-wide association study identified one variant that had not been previously implicated in 5-FU pharmacokinetic or pharmacodynamic pathways and failed to identify association signals in previously identified markers or their imputed proxys [21].

In Taiwan, and most other countries, cancer treatment is conducted by a team. In fact, high-volume physicians represent high-volume teams. It is possible that high-volume physicians, who coordinate large experienced teams, including radiation oncolo- gists, hematology oncologists, radiologists, and specialized nurses, are of paramount importance for the treatment of cancer. Several hypotheses for the volume-outcome relationship have been proposed. The ‘‘practice makes perfect’’ concept suggests that increased caseloads may help physicians or hospital staff develop skills and execute treatment procedures more effectively, as is the case with surgical procedures, chemotherapy, irradiation, and manipulation of radiation oncology teletherapy units. Achieving complete excision with a tumor-free margin with regional lymph node dissection is crucial in the treatment of most cancers. A positive surgical margin and regional lymph node metastasis are the most significant predictive factors for breast cancer, lung cancer, colorectal cancer, and oral cancer [33,34,35], [36,37]. Adequate and well-performed regional lymph node dissection and a successful complete excision of the primary tumor may be the crucial procedures for success in cancer treatment. High-volume surgeons may have the surgical skills and experience necessary to perform these procedures. In treating early-stage breast cancer, Gilligan et al. [38]. reported that high-volume surgeons were significantly more likely to provide care which adheres to National Institutes of Health recommendations because of the higher

A prospective surveillance program with centralized nurse-led data collection was implemented at our institution in 2008; physically fit patients with surgically resected CRC, stages II and III were eligible. The aim of this study was to evaluate the rate of surgical treatment of recurrence with curative intent in our program; secondary outcomes were: colorectal cancer mortality, time to detection of recurrence, survival after treatment of recurrence with curative intent, evaluation of clinical characteristics associated with non- resectable recurrence and diagnostic accuracy of the surveillance model.

Etiologically, colorectal perforations cause by enema ad- ministration can be divided into those that are iatrogenic and those that are secondary to weakness of the colorectal wall. Iat- rogenic perforations can occur as a result of forced introduction of the catheter into the anterior rectum wall, balloon hyperin- lation, or excessive hydrostatic pressure during contrast injec- tion. Perforations secondary to colorectal wall weakness occur in patients with a history of inlammatory bowel disease, acute diverticulitis, or obstructive colorectal processes, as well as in those who have recently undergone a surgical procedure, are of advanced age, or are on corticosteroid therapy, any of which make these patients more susceptible to perforation during the administration of the enema (3) . In such high-risk cases, the use