Choledochal cyst in childhood: review of 30 cases

Objective: To analyze and discuss the clinical data, diagnosis and treatment of a number of patients with cystic dilatation of the common bile duct of a Brazilian pediatric hospital.Methods: We analyzed 30 patients treated at the Martagão Gesteira Institute of Pediatrics and Child Care of the Federal University of Rio de Janeiro for 23 years ,with statistical analysis of epidemiological data, clinical manifestations, diagnosis, treatment and postoperative outcome.Results: We observed a marked female predominance (73.4% of cases), the diagnosis being made in the first decade of life in 90% of patients. The most prevalent clinical manifestation was jaundice (70% of cases) and the classic triad of choledochal cyst was not observed. Abdominal ultrasound was the first imaging examination performed, with a sensitivity of 56.6%, with diagnostic definition in 17 children. Two patients (6.6%) had prenatal diagnosis. All patients underwent surgical treatment, cyst resection with Roux-en-Y hepaticojejunostomy being performed in 80% of cases. The incidence of postoperative complications was 13.3% and the mortality rate was 6.6%, ie two patients were diagnosed with Caroli's disease.Conclusion: The non-observance of the classic triad of choledochal cyst suggests that its incidence is lower than that reported in the medical literature. The surgical treatment of choledochal cysts, with resection and bilioenteric anastomosis, is safe even for small children.

Ultrasound evaluation on carpal tunnel syndrome before and after bariatric surgery

Objective:To evaluate the prevalence of carpal tunnel syndrome in candidates for bariatric surgery comparing with the non-obese population and verify the effects on it of bariatric treatment. Methods:We studiedthree groups of individuals: 1) patients waiting for bariatric surgery (preoperative); 2) individuals who had already undergone the procedure (postoperative); and 3) control group. We collected demographic and clinical data of carpal tunnel syndrome. The Ultrasound examination was carried out to diagnose the syndrome by measuring the median nerve area. Results:We included 329 individuals (114 in the preoperative group, 90 in the postoperative group and 125 controls). There was a higher prevalence of paresthesias (p=0.0003), clinical tests (p=0.0083) on the preoperative group when compared with controls (p<0.00001). There were lowe levels of paresthesias (p=0.0002) and median nerve area (p=0.04) in postoperative patients but with no significant difference in general. A significant difference was found between the preoperative and postoperative groups (p=0.05) in those who performed non-manual work.Conclusion: There was a higher prevalence of carpal tunnel syndrome in the preoperative group compared with the control one, but no significant difference was observed between the pre and postoperative groups in general. There was difference between pre and postoperative groups for non-manual workers.

Resection of liver metastasis from neuroendocrine tumors: evaluation of results and prognostic factors

OBJECTIVES: to determine the prognostic factors that may impact on morbidity and mortality and survival of patients undergoing surgical treatment of liver metastases from neuroendocrine tumors. METHODS: We studied 22 patients undergoing liver resection for metastases from neuroendocrine tumors between 1997 and 2007. Epidemiological and clinical data were correlated with morbidity and mortality and overall and disease-free survivals. RESULTS: twelve patients were male and ten female, with a mean age of 48.5 years. Bilobar disease was present in 17 patients (77.3%). In ten patients (45.5%) the primary tumor originated in the pancreas, terminal ileum in eight, duodenum in two, rectum in one and jejunum in one. Complete surgical resection (R0) was achieved in 59.1% of patients. Eight patients (36.3%) developed complications in the immediate postoperative period, one of them dying from septicemia. All patients undergoing re-hepatectomy and/or two-stage hepatectomy had complications in the postoperative period. The overall survival at one and five years was 77.3% and 44.2%. The disease-free survival at five years was 13.6%. The primary pancreatic neuroendocrine tumor (p = 0.006) was associated with reduced overall survival. Patients with number of metastatic nodules < 10 (p = 0.03) and asymptomatic at diagnosis (p = 0.015) had higher disease-free survival. CONCLUSION: liver metastases originating from pancreatic neuroendocrine tumors proved to be a negative prognostic factor. Symptomatic patients with multiple metastatic nodules showed a significant reduction in disease-free survival.

Visual customer segmentation and behavior analysis : a SOM-based approach

Ett ämne som väckt intresse både inom industrin och forskningen är hantering av kundförhållanden (CRM, eng. Customer Relationship Management), dvs. en kundorienterad affärsstrategi där företagen från att ha varit produktorienterade väljer att bli mera kundcentrerade. Numera kan kundernas beteende och aktiviteter lätt registreras och sparas med hjälp av integrerade affärssystem (ERP, eng. Enterprise Resource Planning) och datalager (DW, eng. Data Warehousing). Kunder med olika preferenser och köpbeteende skapar sin egen ”signatur” i synnerhet via användningen av kundkort, vilket möjliggör mångsidig modellering av kundernas köpbeteende. För att få en översikt av kundernas köpbeteende och deras lönsamhet, används ofta kundsegmentering som en metod för att indela kunderna i grupper utgående från deras likheter. De mest använda metoderna för kundsegmentering är analytiska modeller konstruerade för en viss tidsperiod. Dessa modeller beaktar inte att kundernas beteende kan förändras med tiden. I föreliggande avhandling skapas en holistisk översikt av kundernas karaktär och köpbeteende som utöver de konventionella segmenteringsmodellerna även beaktar dynamiken i köpbeteendet. Dynamiken i en kundsegmenteringsmodell innefattar förändringar i segmentens struktur och innehåll, samt förändringen av individuella kunders tillhörighet i ett segment (s.k migrationsanalyser). Vardera förändringen modelleras, analyseras och exemplifieras med visuella datautvinningstekniker, främst med självorganiserande kartor (SOM, eng. Self-Organizing Maps) och självorganiserande tidskartor (SOTM), en vidareutveckling av SOM. Visualiseringen anteciperas underlätta tolkningen av identifierade mönster och göra processen med kunskapsöverföring mellan den som gör analysen och beslutsfattaren smidigare. Asiakkuudenhallinta (CRM) eli organisaation muuttaminen tuotepainotteisesta asiakaskeskeiseksi on herättänyt mielenkiintoa niin yliopisto- kuin yritysmaailmassakin. Asiakkaiden käyttäytymistä ja toimintaa pystytään nykyään helposti tallentamaan ja varastoimaan toiminnanohjausjärjestelmien ja tietovarastojen avulla; asiakkaat jättävät jatkuvasti piirteistään ja ostokäyttäytymisestään kertovia tietojälkiä, joita voidaan analysoida. On tavallista, että asiakkaat poikkeavat toisistaan eri tavoin, ja heidän mieltymyksensä kuten myös ostokäyttäytymisensä saattavat olla hyvinkin erilaisia. Asiakaskäyttäytymisen monimuotoisuuteen ja tuottavuuteen paneuduttaessa käytetäänkin laajalti asiakassegmentointia eli asiakkaiden jakamista ryhmiin samankaltaisuuden perusteella. Perinteiset asiakassegmentoinnin ratkaisut ovat usein yksittäisiä analyyttisia malleja, jotka on tehty tietyn aikajakson perusteella. Tämän vuoksi ne monesti jättävät huomioimatta sen, että asiakkaiden käyttäytyminen saattaa ajan kuluessa muuttua. Tässä väitöskirjassa pyritäänkin tarjoamaan holistinen kuva asiakkaiden ominaisuuksista ja ostokäyttäytymisestä tarkastelemalla kahta muutosvoimaa tiettyyn aikarajaukseen perustuvien perinteisten segmentointimallien lisäksi. Nämä kaksi asiakassegmentointimallin dynamiikkaa ovat muutokset segmenttien rakenteessa ja muutokset yksittäisten asiakkaiden kuulumisessa ryhmään. Ensimmäistä dynamiikkaa lähestytään ajallisen asiakassegmentoinnin avulla, jossa visualisoidaan ajan kuluessa tapahtuvat muutokset segmenttien rakenteissa ja profiileissa. Toista dynamiikkaa taas lähestytään käyttäen nk. segmenttisiirtymien analyysia, jossa visuaalisin keinoin tunnistetaan samantyyppisesti segmentistä toiseen vaihtavat asiakkaat. Visualisoinnin tehtävänä on tukea havaittujen kaavojen tulkitsemista sekä helpottaa tiedonsiirtoa analysoijan ja päättäjien välillä. Visuaalisia tiedonlouhintamenetelmiä, kuten itseorganisoivia karttoja ja niiden laajennuksia, käytetään osoittamaan näiden menetelmien hyödyllisyys sekä asiakkuudenhallinnassa yleisesti että erityisesti asiakassegmentoinnissa.

Outbreaks of canid herpesvirus 1 disease in puppies in southern Brazil

Abstract: Canid herpesvirus 1 (CHV-1) is a widespread pathogen of dogs and produces infertility, abortions and severe systemic disease in young puppies. Clinical data indicate the circulation of CHV-1 among Brazilian dogs yet definitive diagnosis has rarely been accomplished. This article describes the clinicopathological findings of four independent cases/outbreaks of neonatal disease by CHV-1 in Bulldog puppies followed by virus identification and genetic characterization. Three events occurred in a kennel holding dogs of different breeds at reproductive age (March 2013, October 2013 and April 2014). Puppies from three French or English Bulldog litters, aging 9 to 30 days were affected, presenting dyspnea, agonic breathing, pale mucous, abdominal pain and tension, evolving to death within about 24 hours. At necropsy, the puppies presented necrohemorrhagic hepatitis, multifocal and moderate necrohemorrhagic nephritis and fibrinonecrotic interstitial pneumonia. Virus isolation was positive in clinical specimens from one litter and CHV-1 DNA was detected by PCR in tissues from all four cases. Virus-neutralizing assays with samples of the affected kennel revealed 9/12 adult animals with high antibody titers to CHV-1. Nucleotide sequencing of glycoprotein B, C and D genes revealed 99-100% of identity among the viruses and with CHV-1 sequences available in GenBank. Phylogenetic analyses of gC sequences showed a segregation of the samples, even among three isolates from the same kennel. These findings support CHV-1 infection as the cause of disease and death in these dog litters, reinforcing the need for correct etiologic diagnosis, prevention and immunization against CHV-1 in dogs from Southern Brazil.

Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Benzodiazepines and Cognitive Functioning in Older Adults. With Emphasis on Long-Term Use and Withdrawal

Benzodiazepines (BZD) and benzodiazepine related drugs (RD) are the most commonly used psychotropics among the aged. The use of other psychotropics taken concomitantly with BZD/ RD or their cognitive effects with BZD/RD have not been studied frequently. The aim of this academic thesis was to describe and analyse relationships between the use of BZD/RD alone or concomitantly with antipsychotics, antidepressants, opioids, antiepileptics, opioids and anticholinergics in the aged and their health. Especially, the relationships between long-term use of BZD/RD and cognitive decline were studied. Additionally, the effect of melatonin on BZD/RD withdrawal and the cognitive effects of BZD/RD withdrawal were studied. This study used multiple data sets: the first study (I) was based on clinical data containing aged patients (≥65 years; N=164) admitted to Pori City Hospital due to acute disease. The second data set (Studies II and III) was based on population-based data from the Lieto Study, a clinico-epidemiological longitudinal study carried out among the aged (≥65 years) in the municipality of Lieto. Follow-up data was formed by combining the cohort data collected in 1990-1991 (N=1283) and in 1998-1999 (N=1596) from those who participated in both cohorts (N=617). The third data set (Studies IV and V) was based on the Satauni Study’s data. This study was performed in the City of Pori in 2009-2010. In the RCT part of the Satauni Study, ninety-two long-term users of BZD/RD were withdrawn from their drugs using melatonin against placebo. The change of their cognitive abilities was measured during and after BZD/ RD withdrawal. BZD/RD use was related to worse cognitive and functional abilities, and their use may predict worse cognitive outcomes compared with BZD/RD non-users. Hypnotic use of BZD/RD could be withdrawn with psychosocial support in motivated participants, but melatonin did not improve the withdrawal results compared to those with placebo. Cognitive abilities in psychomotor tests did not show, or showed only modest, improvements for up to six months after BZD/RD withdrawal. This suggests that the cognitive effects of BZD/RD may be longlasting or permanent.

Hb Köln [a2b298(FG5) val-met] identified by DNA analysis in a Brazilian family

Hb Köln was identified by DNA analysis in a Brazilian patient. A four-year old Brazilian female, with jaundice since birth, presented an abnormal band, between A2 and S, in hemoglobin electrophoresis on a cellulose acetate membrane, and a band with electrophoretic migration similar to Hb C on agar gel. Thermic instability and isopropanol precipitation tests were positive. Heinz bodies were observed in the patient’s peripheral blood. Sequencing of the three exons of the b globin gene detected a transition from G to A in the first position of codon 98. This alteration does not create or abolish any known restriction site. In this case, confirmation of the mutation was accomplished by allele-specific oligonucleotide hybridization, which is a simple and fast identification method when the clinical data and hematological and electrophoretic patterns are suggestive of Hb Köln.

Detection and analysis of apoptosis in peripheral blood cells from breast cancer patients

Apoptosis is a well-known specific process of cell death that normally occurs in physiological situations such as tissue or organ development and involution. During tumor growth there is a balance between proliferation and cell death which involves apoptotic mechanisms. In the present study genomic DNAs from 120 breast tumor biopsies were analyzed by agarose gel electrophoresis and none of them presented the fragmentation pattern characteristic of the apoptosis process. However, 33% of the 105 breast cancer patients clearly showed the apoptotic pattern when DNA from blood cells was analyzed. None of the DNAs from healthy volunteer blood cells showed any trace of apoptosis. Since the breast cancer patients were not receiving chemo- or hormone therapy, the possible relationship between blood cortisol levels and the apoptotic pattern found in patient blood cells was investigated. Using a chemoluminescence immunodetection assay, similar cortisol levels were observed in breast cancer patient sera presenting or not apoptotic blood cells and in healthy volunteer sera. Analysis of the clinical data obtained from 60 of these patients showed that patients bearing tumors of smaller size (under 20 mm) were more susceptible to the apoptotic effect in blood cells. According to the Elston grade, it was observed that 7 of 12 patients with grade III tumors (58%) presented apoptotic peripheral blood cells, in contrast to 10 of 48 patients with grade I and grade II tumors. These observations may reflect the immunosuppression characteristic of some breast cancer patients, which may contribute to tumor growth. Therefore, further studies are necessary to elucidate the factor(s) involved in such massive blood cell death.

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma

The etiopathogenesis of vulvar intraepithelial neoplasia (VIN III) and invasive squamous cell carcinoma are largely unknown. Since there are few studies on Brazilian patients, our purpose was to determine the frequency of human papillomavirus (HPV) infection and the expression of p53 in these lesions, and associate them with other factors such as age, morphological subtypes, multicentric and multifocal disease. Thirty-eight cases of VIN III, nine of superficially invasive carcinoma, and 55 of invasive vulvar carcinoma were retrospectively evaluated from 1983 to 1995 for the presence of HPV by immunohistochemistry and in situ hybridization, and for p53 protein expression by immunohistochemistry on paraffin sections. All cases for whom material (slides and paraffin blocks) and clinical data were available were included. HPV and p53 were detected in 57.9 and 21.1% of the VIN III lesions, 33.3 and 66.7% of superficially invasive carcinomas, and 7.3 and 58.2% of invasive squamous cell carcinomas, respectively. HPV infection was associated with younger age in the VIN III and invasive carcinoma groups. In the latter, HPV infection was associated with the basaloid variant. p53 expression rate was higher in superficially invasive and invasive lesions and was not related to HPV infection. Our findings are similar to others and support the hypothesis that there are two separate entities of the disease, one associated with HPV and the other unrelated, with p53 inactivation possibly being implicated in some of the cases.

Noninvasive classification of liver disease in asymptomatic and oligosymptomatic male alcoholics

The predominant type of liver alteration in asymptomatic or oligosymptomatic chronic male alcoholics (N = 169) admitted to a psychiatric hospital for detoxification was classified by two independent methods: liver palpation and multiple quadratic discriminant analysis (QDA), the latter applied to two parameters reported by the patient (duration of alcoholism and daily amount ingested) and to the data obtained from eight biochemical blood determinations (total bilirubin, alkaline phosphatase, glycemia, potassium, aspartate aminotransferase, albumin, globulin, and sodium). All 11 soft and sensitive, and 13 firm and sensitive livers formed fully concordant groups as determined by QDA. Among the 22 soft and not sensitive livers, 95% were concordant by QDA grouping. Concordance rates were low (55%) in the 73 firm and not sensitive livers, and intermediate (76%) in the 50 not palpable livers. Prediction of the liver palpation characteristics by QDA was 95% correct for the firm and not sensitive livers and moderate for the other groups. On a preliminary basis, the variables considered to be most informative by QDA were the two anamnestic data and bilirubin levels, followed by alkaline phosphatase, glycemia and potassium, and then by aspartate aminotransferase and albumin. We conclude that, when biopsies would be too costly or potentially injurious to the patients to varying extents, clinical data could be considered valid to guide patient care, at least in the three groups (soft, not sensitive; soft, sensitive; firm, sensitive livers) in which the two noninvasive procedures were highly concordant in the present study.

Visual analytics for behavioral and niche market segmentation

Companies require information in order to gain an improved understanding of their customers. Data concerning customers, their interests and behavior are collected through different loyalty programs. The amount of data stored in company data bases has increased exponentially over the years and become difficult to handle. This research area is the subject of much current interest, not only in academia but also in practice, as is shown by several magazines and blogs that are covering topics on how to get to know your customers, Big Data, information visualization, and data warehousing. In this Ph.D. thesis, the Self-Organizing Map and two extensions of it – the Weighted Self-Organizing Map (WSOM) and the Self-Organizing Time Map (SOTM) – are used as data mining methods for extracting information from large amounts of customer data. The thesis focuses on how data mining methods can be used to model and analyze customer data in order to gain an overview of the customer base, as well as, for analyzing niche-markets. The thesis uses real world customer data to create models for customer profiling. Evaluation of the built models is performed by CRM experts from the retailing industry. The experts considered the information gained with help of the models to be valuable and useful for decision making and for making strategic planning for the future.

Furosemide is associated with acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients. Diuretics are used without any evidence demonstrating a beneficial effect on renal function. The objective of the present study is to determine the incidence of AKI in an intensive care unit (ICU) and if there is an association between the use of furosemide and the development of AKI. The study involved a hospital cohort in which 344 patients were consecutively enrolled from January 2010 to January 2011. A total of 132 patients (75 females and 57 males, average age 64 years) remained for analysis. Most exclusions were related to ICU discharge in the first 24 h. Laboratory, sociodemographic and clinical data were collected until the development of AKI, medical discharge or patient death. The incidence of AKI was 55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI = 1.57-6.80, and age: OR = 1.02 (95%CI = 1.00-1.04). Analysis of the subgroup of patients with septic shock showed that the odds ratio of furosemide was 5.5 (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic shock were predictors of AKI in critically ill patients. Use of furosemide in the subgroup of patients with sepsis/septic shock increased (68.4%) the chance of development of AKI when compared to the sample as a whole (43.9%).

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT) after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT) maintenance therapy. We compared time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45); the median TTP (MTTP) for the complete treatment was 9.43 months (95%CI=8.38-10.48 months) for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004) for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months) for the CMT group and 2.0 months (95%CI=1.63-2.38 months) for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile.