Trends in presentation, treatment and survival of 1777 patients with colorectal cancer over a decade: a Biobank study.

BACKGROUND: Most survival data in colorectal cancer (CRC) is derived from clinical trials or register-based studies. Hospital Biobanks, linked with hospital electronic records, could serve as a data-gathering method based on consecutively collected tumor samples. The aim of this Biobank study was to analyze survival of colorectal patients diagnosed and treated in a single-center university hospital over a period of 12 years, and to evaluate factors contributing to outcome. MATERIAL AND METHODS: A total of 1777 patients with CRC treated during 2001-2012 were identified from the Auria Biobank, Turku, Finland. Longitudinal clinical information was collected from various hospital electronic records and date and cause of death obtained from Statistics Finland. RESULTS: Cancer-specific, overall and disease-free survival was higher in patients diagnosed during 2004-2008 as compared with patients diagnosed in 2001-2003. Further improvement was not seen during years 2009-2012. Potential factors contributing to the improvement were introduction of multidisciplinary meetings, centralization of rectal cancer surgery, use of adjuvant chemotherapy and systematic preoperative radiotherapy of rectal cancer. The proportion of patients with stage I-IV CRC remained similar over the study period, but a marked decrease in non-metastatic rectal cancer with biopsy only (locally advanced disease) was observed. In stage I-III rectal cancer, Cox multivariate analysis suggested age, comorbidity, R1 resection, T staging and tumor grade as prognostic factors. In colon cancer, prognostic factors were age, comorbidity, gender and presence of lymph node metastases. CONCLUSIONS: Organizational changes in the treatment of CRC patients made since 2004 coincide with improved survival in CRC and a marked reduction in locally advanced rectal cancers. The clinical presentation of CRC has remained similar between 2001 and 2012.

[Streamlined treatment pathway for a colorectal cancer patient]. / Suolistosyöpäpotilaan hoitopolku sujuvaksi.

The organization of colorectal cancer patient treatment, the pathway, is an important component of the quality of care of a large patient group as nearly 3000 colorectal cancer patients are diagnosed and treated annually in Finland. By designing and describing the whole pathway, the more streamlined approach can be made and thus improve patient care. Multidisciplinary team work between colorectal surgeons, oncologists, pathologists and radiologists is flexible team work, having been proven to improve overall treatment results. This method of working together is also a good tool for the development of the pathway to a better organized treatment.

Elective laparoscopic cholecystectomy for symptomatic uncomplicated gallstone disease: do the symptoms disappear?

BACKGROUND: Symptomatic gallstone disease is considered an indication for cholecystectomy. A considerable proportion of patients may experience persistent symptoms after surgery. The purpose of the present study was to find out the rate of symptom persistence after elective laparoscopic cholecystectomy (LC) performed for symptomatic uncomplicated gallstone disease and, in particular, to clarify whether the recurrence rate differs according to the severity of preoperative symptoms. METHODS: During a 10-year period (1992-2001), 1,101 patients underwent elective LC at Turku City Hospital for Surgery. A questionnaire concerning the intensity of preoperative symptoms, persistence of symptoms postoperatively, and overall satisfaction with the outcome of the procedure was sent to patients. A total of 677 patients [mean age (range) 59 (21-94) years; 554 (83.1%) females] with uncomplicated gallstone disease returned the completed form. RESULTS: Overall, 380 (57%) patients reported attacks of intense upper abdominal pain, and 287 (43%) reported episodic mild abdominal symptoms as the prevailing preoperative symptom. Two hundred and forty-eight (37%) patients continued to have abdominal symptoms after the operation. Among those with predominantly mild abdominal symptoms preoperatively, 119 (41%) reported the persistence of symptoms after the operation, while in the group with mainly severe upper abdominal pain attacks, 129 (33%) patients had recurrences (p = 0.052). CONCLUSIONS: According to our data, more than one-third of patients with symptomatic uncomplicated gallstone disease experienced persistent symptoms after elective LC. Patients with mild preoperative symptoms seemed to have more recurrences than those with severe symptoms, although the difference was not statistically significant.

Late complications related to palliative stenting in patients with obstructing colorectal cancer.

INTRODUCTION: Self-expanding metal stents (SEMSs) are increasingly used for the palliative treatment of incurable obstructing colorectal cancer. The aim of the current study was to evaluate clinical outcome, including technical and clinical success of stenting, and to identify factors associated with late complications of SEMS in palliation of incurable obstructing colorectal cancer. MATERIAL AND METHODS: Between 2003 and 2010 details of 56 patients who underwent an attempt of SEMS insertion for obstructive incurable colorectal cancer at Turku University Hospital were recorded to our database prospectively and analyzed retrospectively. RESULTS: Technical success was achieved in 42 patients (75%) and clinical success in 39 patients (70%). Late complications related to SEMS occurred in 13 patients (31%). Ten patients (24%) needed re-intervention because of a complication: Eight ostomies, one Hartmann´s procedure due to late perforation and one re-stenting because of stent migration. Three patients with stent-related complications were treated conservatively. Chemotherapy and prolonged survival were risk factors for SEMS-related late complications and re-intervention. CONCLUSION: SEMS insertion is a feasible procedure for the palliative treatment of obstructing colorectal cancer in patients with severe comorbidities and short life expectancy. However, for patients who are candidates for chemotherapy and have a longer life expectancy, other treatment options such as palliative tumor resection should also be considered.

Wafer-Scale Graphene Field-Effect Transistor Biosensor Arrays with Monolithic CMOS Readout.

The reliability of analysis is becoming increasingly important as point-of-care diagnostics are transitioning from single-analyte detection toward multiplexed multianalyte detection. Multianalyte detection benefits greatly from complementary metal-oxide semiconductor (CMOS) integrated sensing solutions, offering miniaturized multiplexed sensing arrays with integrated readout electronics and extremely large sensor counts. The development of CMOS back end of line integration compatible graphene field-effect transistor (GFET)-based biosensing has been rapid during the past few years, in terms of both the fabrication scale-up and functionalization toward biorecognition from real sample matrices. The next steps in industrialization relate to improving reliability and require increased statistics. Regarding functionalization toward truly quantitative sensors, on-chip bioassays with improved statistics require sensor arrays with reduced variability in functionalization. Such multiplexed bioassays, whether based on graphene or on other sensitive nanomaterials, are among the most promising technologies for label-free electrical biosensing. As an important step toward that, we report wafer-scale fabrication of CMOS-integrated GFET arrays with high yield and uniformity, designed especially for biosensing applications. We demonstrate the operation of the sensing platform array with 512 GFETs in simultaneous detection for the sodium chloride concentration series. This platform offers a truly statistical approach on GFET-based biosensing and further to quantitative and multianalyte sensing. The reported techniques can also be applied to other fields relying on functionalized GFETs, such as gas or chemical sensing or infrared imaging.

[Rationale for antimicrobial prophylaxis in surgery and its implementation in Finnish patient care]. / Kirurgisen mikrobilääkeprofylaksin perusteet ja toteutuminen suomalaisessa sairaanhoidossa.

Country-specific differences in bacterial antibiotic resistances cause variability in recommendations given in different countries. Mutually approved national expert and hospital-specific practices are therefore beneficial. Selection of the best prophylactic antimicrobial drug and correct timing of drug dosing are of high significance. In the light of our questionnaire survey prophylactic practices are relatively consistent in Finland. Hospitals have operation-specific recommendations on prophylaxis, but adherence to them is scarcely monitored. In fact, hospitals should invest in such monitoring systems.

Elective laparoscopic cholecystectomy: the effect of age on conversions, complications and long-term results.

BACKGROUND/AIMS: The purpose of the present study was to analyze the appropriateness and long-term results of elective laparoscopic cholecystectomy in the treatment of gallstone disease in the elderly. METHODS: We studied all elderly (≥75 years) patients (n = 80) who underwent laparoscopic cholecystectomy at our institution during the years 1992-2001. Two control groups (65-74 years and <65 years) included the same amount of patients. For determining the long-term results, we asked the patients to specify their overall satisfaction with the results of the procedure (very satisfied, satisfied, no effect, worse). RESULTS: There were no statistically significant differences in mean operative time (61, 65, 72 min) or conversions to open surgery (6, 11, 16%) between the age groups (<65, 65-74, ≥75 years). The mean hospitalization time (2.1, 3.3, 4.4 days) and complications (0, 11, 13%) increased with the age of the patients. Neither severe complications nor mortality were encountered. The vast majority of the patients were very satisfied or satisfied with the long-term results of the procedure in all age groups (97% <65 years, 83% 65-74 years, 80% ≥75 years). CONCLUSION: Elective laparoscopic cholecystectomy is also a safe and feasible operation with good long-term results in the elderly.

CMOS-integrated film bulk acoustic resonators for label-free biosensing.

The throughput is an important parameter for label-free biosensors. Acoustic resonators like the quartz crystal microbalance have a low throughput because the number of sensors which can be used at the same time is limited. Here we present an array of 64 CMOS-integrated film bulk acoustic resonators. We compare the performance with surface plasmon resonance and the quartz crystal microbalance and demonstrate the performance of the sensor for multiplexed detection of DNA.

[The bowel should not be emptied before colon surgery]. / Suolta ei pidä tyhjentää ennen paksusuolileikkausta.

Mechanical aspiration of intestinal contents has been utilized in colon surgery for decades without scientific proof of the benefits of the procedure. According to randomized studies performed on the subject, mechanical cleaning of the bowel before surgical operations of the colon is unnecessary and even harmful to the patient. Intestinal operations must be carried out applying careful surgical aseptic techniques and appropriate antibiotic prophylaxis, and it is recommendable to abandon the routine emptying in surgical operations of the large intestine.

Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT).

BACKGROUND: Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting. METHODS AND RESULTS: Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58+/-6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 microg of DNA with 2000 microL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer's lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups. CONCLUSIONS: Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.

Concomitant impairment of left ventricular systolic and diastolic function during doxorubicin therapy: a prospective radionuclide ventriculographic and echocardiographic study.

Thirty adult lymphoma patients were studied prospectively with serial radionuclide ventriculography (RVG) and echocardiography (ECHO) to investigate whether changes in left ventricular (LV) diastolic function precede the impairment of LV systolic function during doxorubicin therapy. The patients received 8-10 cycles of CHOP to a cumulative doxorubicin dose of 400-500 mg/m2. RVG and ECHO were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m2. Left ventricular ejection fraction (LVEF) decreased from 58 +/- 1.3 to 49.6 +/- 1.7% (p < 0.001) and from 58 +/- 1.7 to 52.5 +/- 1.3% (p = 0.036) as assessed with RVG and 2D ECHO, respectively. Of the diastolic ECHO doppler indices peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm/s (p = 0.008) and LV filling during the first 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (p < 0.001). The decrease in LVEF was statistically significant after the cumulative doxorubicin dose of 200 mg/m2 as assessed with RVG and after 400 mg/m2 as assessed with 2D ECHO. The decrease in 1/3FF reached the statistical significance after the cumulative doxorubicin dose of 400 mg/m2 and the decrease in peak E wave velocity after 500 mg/m2. This study shows that during doxorubicin therapy there are significant changes both in systolic and diastolic LV function. In addition, these changes manifest at relatively low cumulative doxorubicin doses and occur concomitantly. Thus, the assessment of diastolic function provides no advantage over monitoring systolic function during doxorubicin therapy.

Patient's age should not play a key role in clinical decisions on surgical treatment of rectal cancer.

BACKGROUND AND AIMS: Recent advances in surgical techniques and adjuvant treatments have decreased morbidity and mortality in patients with rectal cancer. The aim of this study was to clarify the effects of aging on the choice, feasibility and safety of various treatment modalities in patients with rectal cancer. PATIENTS AND METHODS: During 2003-2006, a total of 274 rectal cancers were diagnosed at Turku University Central Hospital. Patient and tumor characteristics, treatment modalities chosen, and complications were recorded, and patients were followed up prospectively for 1-3 years after treatment. Patients were then divided into two groups: under 75 (n=181) and 75 years or older (n=93) at the moment of diagnosis. Patient data in the two age groups were analysed and compared with each other. RESULTS: Of the total of 274 patients with rectal cancer, 243 (89%) underwent surgery. The percentage of patients operated was higher (p=0.03) in the younger (92%) than in the older group (83%). The main reasons for non-operative or palliative treatment were severe concomitant diseases and metastasized cancer. Preoperative radiation therapy was given more often (p<0.01) to young (72%) than old (27%) patients. With these selections, there was no difference in 30-day postoperative mortality (1% vs 1%, ns) or postoperative complications (22% vs 34%, ns) between two groups. CONCLUSION: With preoperative selection, patients over 75 with rectal cancer are suitable for major surgery, as morbidity and mortality rates are comparable to those in younger patients.

Adoption of self-expanding metallic stents in the palliative treatment of obstructive colorectal cancer-look out for perforations!

Self-expanding metallic stents (SEMSs) are increasingly used for the palliative treatment of inoperable colorectal cancer. The aim of the current study was to analyze the safety and efficacy of SEMS in the palliative treatment of obstructive colorectal cancer. Between 2003 and 2006, SEMS placement was attempted in 26 patients suffering from inoperable obstructive colorectal cancer. The recovery of the patients and the outcome of this treatment modality were analyzed prospectively. SEMS was successfully inserted in 19 (73%) of 26 patients. In 16 (84%) of these 19 cases, the placement of SEMS was the definitive treatment of colorectal obstruction and no additional surgical palliation was needed. There were 3 (16%) colonic perforations related to stent application. SEMS insertion seems to be an effective alternative in the palliative treatment of patients with malignant colorectal obstruction. However, perforation is a dangerous complication of the procedure.

Comparison of long-term outcome of laparoscopic and conventional nissen fundoplication: a prospective randomized study with an 11-year follow-up.

OBJECTIVE: The aim of this study was to compare the long-term objective and subjective outcomes of laparoscopic and open Nissen fundoplication in a randomized clinical trial with an 11-year follow-up. SUMMARY BACKGROUND DATA: Laparoscopic Nissen fundoplication has become the method of choice in antireflux surgery, replacing its open counterpart despite the lack of long-term results from controlled clinical studies. METHODS: Between April 1992 and June 1995, 110 consecutive patients were randomized to either laparoscopic (LAP) or conventional (open) Nissen fundoplication. The objective long-term follow-up consisted of an upper gastrointestinal endoscopy and a clinical assessment; the subjective long-term outcome was investigated by personal interviews using a structured questionnaire. RESULTS: Forty-nine patients in the LAP group and 37 patients in the open group were available for evaluation. Late subjective results, including postoperative symptoms and evaluation of the surgical result, were similar in both groups. With the benefit of hindsight, 73.7% of the patients in the open group and 81.8% in the LAP group would again choose surgical treatment (P = 0.3042). In the LAP group, there were 5 (13.2%) partially or totally disrupted plications compared with the 14 (40.0%) disrupted plications in the open group (P = 0.0152). There were 10 incisional hernias in the open group compared with none in the LAP group (P < 0.001). CONCLUSIONS: At long-term follow-up, the open and LAP approaches for the Nissen fundoplication have similar long-term subjective symptomatic outcome despite the significantly higher incidence of incisional hernias and defective fundic wraps at endoscopy in the open group defining laparoscopic Nissen fundoplication as the procedure of choice in surgical management of gastroesophageal reflux disease.

Increased levels of Candida albicans mannan-specific T-cell-derived antigen binding molecules in patients with invasive candidiasis.

In addition to cytokines, CD4+ T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs). These antigen-specific immunoproteins are thought to have immunoregulatory properties in the suppression of cell-mediated immunity (CMI) because they often associate with interleukin-10 (IL-10) and transforming growth factor beta. Decreased CMI causes susceptibility to infections caused by organisms which are normally nonpathogenic. In this situation, e.g., Candida albicans saprophytism may develop into invasive candidiasis. The difficult diagnosis of invasive candidiasis is based on the findings obtained from blood cultures and with tissue biopsy specimens, with some additional diagnostic value gained by the detection of Candida albicans mannan antigenemia and antimannan antibodies. In the present study, Candida albicans mannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive candidiasis (n = 11), Candida colonization (n = 11) and noncolonization (n = 10), recurrent vulvovaginal candidiasis (n = 30), and atopic eczema dermatitis syndrome (n = 59) and healthy controls (n = 30) were analyzed. For 14 participants, the effect of mannan stimulation on TABM production and gamma interferon (IFN-gamma) and IL-4 mRNA expression by peripheral blood lymphocytes was also studied. It was demonstrated that CAM-TABM production was the highest in patients with invasive candidiasis and that CAM-TABM levels could distinguish Candida-colonized patients from noncolonized patients. In addition, the CAM-TABM level was directly related to mRNA expression for IL-4 but not IFN-gamma. These results reinforce the view that TABMs are associated with decreased CMI, immunoregulation, and the T-helper cell 2-type immune response.