Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I-III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection.

BACKGROUND: To establish the impact of re-stratification on the outcomes of patients (stage I-III right-sided colon cancer) based on the presence/absence of occult tumor cells (OTC) and/or metastatic lymph nodes in the different levels of surgical dissection. METHODS: Consecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3. RESULTS: Eighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively. CONCLUSION: This re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival. CLINICAL TRIAL: "Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography" registered at http://clinicaltrials.gov/ct2/show/NCT01351714.

Interactions of occult tumor spread and surgical technique on overall and disease-free survival in patients operated for stage I and II right-sided colon cancer.

PURPOSE: To determine if "medial to lateral" (ML) dissection with devascularization first is superior to "lateral to medial" (LM) dissection regarding numbers of lymph node micro metastases (MM) and isolated tumor cells (ITC) as well as 5-year disease-free (5YDFS) and 5-year overall survival (5YOS) in stage I/II right-sided colon cancer. METHODS: Two datasets are used. ML group consists of consecutive stage I/II patients from a prospective trial. LM group is the original dataset from a previous publication. All harvested lymph nodes are examined with monoclonal antibody CAM 5.2 (immunohistochemically). Lymph node harvest and 5YOS/5YDFS were compared between ML/LM groups, stage I/II tumors and MM/ITC presence/absence. RESULTS: 117 patients included ML:51, LM:66. MM/ITC positive in ML 37.3% (19/51), LM 31.8% (21/66) p = 0.54. The 5YDFS for patients in ML 70.6% and LM 69.7%, p = 0.99, 5YOS: 74.5% ML and 71.2% LM (p = 0.73). No difference in 5YDFS/5YOS between groups for Stage I/II tumors; however, LM group had an excess of early tumors (16) when compared to ML group, while lymph node harvest was significantly higher in ML group (p < 0.01) 15.1 vs 26.7. 5YDFS and 5YOS stratified by MM/ITC presence/absence was 67.5%/71.4%, p = 0.63, and 75.0%/71.4%, p = 0.72, respectively. Death due to recurrence in MM/ITC positive was significantly higher than MM/ITC negative (p = 0.012). CONCLUSION: Surgical technique does not influence numbers of MM/ITC or 5YDFS/5YOS. Presence of MM/ITC does not affect 5YOS/5YDFS but can be a potential prognostic factor for death due to recurrence. CLINICAL TRIAL: Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography" registered at http://clinicaltrials.gov/ct2/show/NCT01351714 .

Associations between schizophrenia polygenic risk and apathy in schizophrenia spectrum disorders and healthy controls.

OBJECTIVE: Apathy is a central predictor of a poor functional outcome in schizophrenia. Schizophrenia polygenic risk scores (PRSs) are used to detect genetic associations to key clinical phenotypes in schizophrenia. We explored the associations between schizophrenia PRS and apathy levels in schizophrenia spectrum disorders (n = 281) and matched healthy controls (n = 298), and further how schizophrenia PRS contributed in predicting apathy when added to premorbid and clinical factors in the patient sample. METHOD: Schizophrenia PRSs were computed for each participant. Apathy was assessed with the Apathy Evaluation Scale. Bivariate correlation analyses were used to investigate associations between schizophrenia PRS and apathy, and between apathy and premorbid and clinical factors. Multiple hierarchical regression analyses were employed to evaluate the contributions of clinical variables and schizophrenia PRS to apathy levels. RESULTS: We found no significant associations between schizophrenia PRS and apathy in patients and healthy controls. Several premorbid and clinical characteristics significantly predicted apathy in patients, but schizophrenia PRS did not. CONCLUSION: Since the PRSs are based on common genetic variants, our results do not preclude associations to other types of genetic factors. The results could also indicate that environmentally based biological or psychological factors contribute to apathy levels in schizophrenia.

Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.

MRI defecography of the ileal pouch-anal anastomosis-contributes little to the understanding of functional outcome.

PURPOSE: Variability in functional outcome after ileal pouch-anal anastomosis (IPAA) is to a large extent unexplained. The aim of this study was to use MRI to evaluate the morphology, emptying pattern and other pathology that may explain differences in functional outcome between well-functioning and poorly functioning pouch patients. A secondary aim was to establish a reference of normal MRI findings in pelvic pouch patients. METHODS: From a previous study, the best and worst functioning patients undergoing IPAA surgery between 2000 and 2013 had been identified and examined with manovolumetric tests (N = 47). The patients were invited to do a pelvic MRI investigating pouch morphology and emptying patterns, followed by a pouch endoscopy. RESULTS: Forty-three patients underwent MRI examination. We found no significant morphological or dynamic differences between the well-functioning and poorly functioning pouch patients. There was no correlation between urge volume and the volume of the bony pelvis, and no correlation between emptying difficulties or leakage and dynamic MRI findings. Morphological MRI signs of inflammation were present in the majority of patients and were not correlated to histological signs of inflammation. Of the radiological signs of inflammation, only pouch wall thickness correlated to endoscopic pouchitis disease activity index scores. CONCLUSION: It seems MRI does not increase the understanding of factors contributing to functional outcome after ileal pouch-anal anastomosis. Unless there is a clinical suspicion of perianal/peripouch disease or pelvic sepsis, MRI does not add value as a diagnostic tool for pelvic pouch patients. Endoscopy remains the golden standard for diagnosing pouch inflammation.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Persistent increase in TNF and IL-1 markers in severe mental disorders suggests trait-related inflammation: a one year follow-up study.

OBJECTIVE: We evaluated if plasma levels of inflammatory markers are persistently altered in severe mental disorders with psychotic symptoms or associated with state characteristics in a longitudinal study. METHODS: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF), and osteoprotegerin (OPG) were measured in schizophrenia (n = 69) and affective (n = 55) spectrum patients at baseline and at one-year follow-up, and compared to healthy controls (HC) (n = 92) with analysis of covariance. Association between change in symptoms and inflammatory markers was analyzed with mixed-effects models. RESULTS: sTNF-R1 was higher in the schizophrenia (P < 0.0001) and affective disorders (P = 0.02) compared to HC, while IL-1Ra was higher in schizophrenia (P = 0.01) compared to HC at one year follow-up. There were no significant differences between schizophrenia and affective groups; however, levels in the affective group were in between schizophrenia and HC for sTNF-R1 and IL-1Ra. There were no significant associations between change in symptoms and inflammatory markers. CONCLUSION: Persistently increased sTNF-R1 and IL-1Ra after one year in patients with severe mental disorders primarily reflecting data from the schizophrenia group may suggest that inflammation is a trait phenomenon, and not only the result of stress-related mechanisms associated with acute episodes.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Restorative proctocolectomy with two different pouch designs: few complications with good function.

AIM: The object of this study was to compare function and quality of life after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) surgery having two different pouch designs. METHOD: Patients having RPC in an academic unit from 2000 who had had the loop-ileostomy closed by June 2013 were identified from the hospital medical records. They were sent a questionnaire regarding quality of life and interviewed using a pouch function score (PFS) described by Oresland (score 0-16, higher scores denote worse function). RESULTS: One hundred and three patients underwent surgery, of whom 56 had a J-pouch design and 47 a K-pouch design, this being a double-folded Kock pouch without the nipple valve. No patients have had the pouch removed or defunctioned due to failure at a mean of 8 years. The reoperation rate was 11.6%. The mean PFS was 5.43 and 5.27 for J- and K-pouches, respectively (P = 0.766). More patients with a J-pouch reported a social handicap due to poor bowel function (P = 0.041). Patients with a PFS ≥ 8 had a poorer quality of life. A score of ≥ 8 was reported by 16% of K-pouch and 25% of J-pouch patients (P = 0.29). CONCLUSION: RPC is a safe procedure with a low complication rate and good functional outcome. Small improvements in function have an impact on a patient's quality of life. Although the J-pouch is the most commonly used, the K-pouch has some advantages. Other pouch designs deserve further evaluation.

The level of illicit drug use is related to symptoms and premorbid functioning in severe mental illness.

OBJECTIVE: There is conflicting data on drug abuse and outcome in severe mental illness. This study aims to investigate if the amount of illicit psychoactive drug use is related to symptom load or premorbid functioning across diagnosis in patients with severe mental illness. METHOD: Symptom load, sociodemographic status, premorbid functioning and the level of use of illicit psychoactive drugs were assessed in 423 subjects with schizophrenia or bipolar disorder in a cross-sectional study. RESULTS: High amount of illicit drug use was associated with poorer premorbid academic functioning. In schizophrenia, there was a significant positive association between amount of drug use and severity of psychiatric symptoms. The association between symptom load and drug use was significant after controlling for premorbid functioning. CONCLUSION: The results suggest a direct association between the quantity of current drug use and more severe symptoms in schizophrenia. Poor premorbid functioning was related to high amount of use, but did not explain the difference in symptom load.

Illicit drug use in patients with psychotic disorders compared with that in the general population: a cross-sectional study.

OBJECTIVE: Prevalence estimates of illicit drug use in psychotic disorders vary between studies, and only a few studies compared prevalence estimates with those in the general population. METHOD: Cross-sectional study comparing 148 stable-phase patients with schizophrenia or bipolar disorder with 329 representative general citizens of Oslo. A total of 849 patients from the same hospital department in the same time period constituted a patient reference group. RESULTS: Lifetime illicit drug use was 44% higher (P < 0.001) in study patients than in the general population sample; while lifetime use of amphetamine/cocaine was 160% higher (P < 0.001). No differences were found between user groups for sociodemographic characteristics. CONCLUSION: Patients with psychotic disorders in stable phase had a markedly higher lifetime use of any illicit substance, especially amphetamine/cocaine, than the general population. They also seemed to use drugs more periodically. The same sociodemographic characteristics were associated with increased illicit drug use in both groups.

Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder have partly overlapping clinical profiles, which include an over-representation of substance-use behaviour. There are few previous studies directly comparing substance-use patterns in the two disorders. The objective of the present study was to compare the prevalence of substance use in schizophrenia and bipolar disorder, and investigate possible differences in pattern and frequency of use. METHOD: A total of 336 patients with schizophrenia or bipolar spectrum disorder from a catchment area-based hospital service were included in a cross-sectional study. In addition to thorough clinical assessments, patients were interviewed about drug-use history, habits and patterns of use. The prevalence and drug-use patterns were compared between groups. RESULTS: Patients with bipolar disorder had higher rates of alcohol consumption, while schizophrenia patients more often used centrally stimulating substances, had more frequent use of non-alcoholic drugs and more often used more than one non-alcoholic drug. Single use of cannabis was more frequent in bipolar disorder. CONCLUSION: The present study showed diagnosis-specific patterns of substance use in severe mental disorder. This suggests a need for more disease-specific treatment strategies, and indicates that substance use may be an important factor in studies of overlapping disease mechanisms.

[Rehabilitation of patients with chronic mental illness]. / Rehabilitering av psykiatriske langtidspasienter.

BACKGROUND: In Norway, the follow-up of patient with severe mental illness was redefined in the early 1990s. The number of inpatient beds in psychiatric hospitals was reduced and new methods for rehabilitation and follow-up tried out. In 1994, Vindern community psychiatric centre set up a special outpatient team for the follow-up of this group of patients. The aim of this study is to give an account of the status of these patients and to evaluate the rehabilitation programme. MATERIAL AND METHODS: All 181 patients admitted for follow-up by the team were included in the study. Data were drawn from yearly questionnaire surveys conducted between 1994 and 1999. RESULTS: 118 (65%) patients were diagnosed with schizophrenia; 32 (18%) had a personality disorder. 93 (51%) were readmitted to hospital during the five years of follow-up. Drug abuse was a problem for 58 (32%). 114 (63%) received a disability pension. Over the period, 39 patients were transferred to follow-up in primary care. INTERPRETATION: Chronic mentally ill patients are a heterogeneous population. Though they have a long history of contact with psychiatric health services, they continue to live with a heavy burden of symptoms and dysfunction. The number of patients with personality disorders was greater than expected. The course, duration and severity of their illness was much like that of the schizophrenics.

Gut perforation caused by biliary endoprosthesis.

Two cases are reported of perforation of the gut caused by biliary endoprosthesies in the three-year period 1993-1995. The first patient was an 81-year-old man who had perforation of the terminal ileum caused by a straight 10 French/7 cm stent which had been dislodged from the bile duct; he underwent laparotomy but did not recover. The second patient was an 86-year-old man who had perforation of the sigmoid colon caused by a straight 7 French/5 cm stent left in the duodenum during a stent exchange procedure; he was successfully treated laparoscopically. Two cases of gut perforation in a three-year period is a rather high rate of this rare complication of placement of biliary endoprostheses.

Laparoscopic and open operation in patients with perforated peptic ulcer.

OBJECTIVES: To compare the results of laparoscopic and open operations in patients with perforated peptic ulcer. DESIGN: Retrospective analysis. SETTING: Central hospital, Norway. SUBJECTS: 74 patients (36 men, 38 women, median age 69.5 years (18-86)) admitted with perforated peptic ulcers from November 1991-May 1996. INTERVENTIONS: Suture of the ulcer, patching with the greater omentum and lavage, in 49 by open operation and 25 laparoscopically. MAIN OUTCOME MEASURES: Duration of postoperative hospital stay, operating time, number of doses of analgesic, postoperative body temperature, complications, and mortality. RESULTS: There was a significant difference (p = 0.0001) in median operating time: 100 minutes (range 48-160) in the laparoscopic group and 50 minutes (range 20-160) in the open group. The median hospital stay was 8 days in both groups: range 3-23 days in the laparoscopic group and 2-28 days in the open group. There were no significant differences between the two groups with regard to median number of doses of analgesic, median body temperature, complications or mortality. CONCLUSION: Laparoscopic operation for perforated peptic ulcer can be considered as safe as open operation.

[Laparoscopic splenectomy]. / Laparoskopisk splenektomi.

From 1995 to 1998, 14 patients have been treated with laparoscopic splenectomy. Seven patients had immune thrombocytopenic purpura (ITP), six hereditary spherocytosis and one chronic myelomonocytic leukaemia with trombocytopenia. 12 of the patients had normal or nearly normal sized spleen. Median duration of surgery was 156 minutes and the median postoperative hospital stay four days. All operations were completed laparoscopically. Three patients had postoperative fever without any sign of infection, one developed urinary retention and one was readmitted with pneumonia. The patient with chronic myelomonocytic leukaemia died 15 days postoperatively from an intracerebral bleeding. Two patients suffer from relapse of trombocytopenia, one is treated with steroids. Laparoscopic splenectomy can be performed safely in patients with normal sized spleen with all the advantages of minimal access surgery. However, problems related to identification of accessory spleens and splenectomy in patients with splenomegali, should be further evaluated.