Clinical and Experimental Studies on Gastrointestinal Anastomoses and Colorectal Cancer

The first section of this thesis discusses the role of stapling techniques in surgical practice. A prospective controlled clinical trial is described, where surgical stapling techniques were compared with conventional manual suturing techniques in the construction of gastrointestinal anastomoses. The following section deals with work on recurrence of colorectal cancer following surgical treatment. Two clinical studies are presented in this section, where "anastomotic techniques" and "anastomotic leaks" are examined respectively in relation to tumour recurrence. The final section of the thesis describes experimental studies in a rodent model, which were designed and conducted to investigate the association between anastomotic leaks and peri-anastomotic tumour growth. Suturing or stapling in gastrointestinal surgery Between April 1985 and April 1989 1,161 consecutive patients undergoing surgery under the care of 13 consultant surgeons throughout the West of Scotland and Highland regions were studied prospectively. All patients had operations that entailed the construction of a gastrointestinal anastomosis. If, at the time of surgery suturing and stapling techniques were considered equally appropriate, the method of anastomotic construction was determined by randomisation. Methods of data collection, bowel preparation, antibiotic prophylaxis, anastomotic materials and anastomotic techniques were standardised by the study protocol. Four hundred and ninety six patients received sutured and 508 received stapled anastomoses. In the remaining 157 patients randomisation was considered inappropriate. All patients were followed until death or discharge from the hospital. The incidence of clinically evident anastomotic dehiscence was 3. 3% in patients with sutured anatomoses, compared with 4.7% in the stapled group (p< 0.22). Sub-clinical (radiologically detected) leaks were encountered with a significantly higher frequency in the sutured group (14.4% versus 5.2%; p < 0.05). Surgical stapling also afforded significantly quicker anastomoses and operations (Mean anastomosis time + SEM: 28.1 +/-0.7 versus 14.3 +/-0.5 minutes, p< 0.001; Mean operating time +/-SEM: 115.5 +/-2.4 versus 103.9 +/-2.2 minutes, p <0.001). With regard to other important outcome measures such as operative mortality, incidence of infective complications, recovery of gastrointestinal function and duration of hospital stay, suturing and stapling techniques produced comparable results. Further detailed analyses are presented, where the randomised and non-randomised patients were stratified according to anastomotic technique and various surgical categories. These data are hoped to provide guidance to surgeons in their selection of anastomotic technique. Anastomotic techniques and recurrence of colorectal cancer Recently some concern has been expressed in the literature regarding a potential adverse influence on the recurrence of rectal cancer associated with the use of stapling techniques. Prompted by these reports, the effect of anastomotic technique on the incidence of recurrence following potentially curative resections was studied in 294 patients. One hundred and forty two of these patients had their anastomoses randomised to suturing and 152 to stapling. By the end of the second postoperative year the incidence of tumour recurrence (+/-SEM) was 29.4% (4.4%) in the sutured group, compared with 19.1% (3.9%) in the stapled group (p< 0.05). Cancer specific mortality was also significantly higher in patients with sutured anatomoses (22.3% +/-4.1% versus 10.9% +/-3.0% at 24 months, p< 0.01). Further analysis revealed that the influence of anastomotic technique on recurrence and mortality rates was independent of tumour stage and other co-variates. These results suggest that in patients undergoing potentially curative resections for colorectal cancer, the use of stapling instruments for anastomotic construction may be associated with a significant reduction in recurrence and cancer specific mortality rates compared with conventional manual suturing techniques. Potential explanations for this previously unreported observation are discussed. (Abstract shortened by ProQuest.)

The prognostic relationship of 18F-FDG PET/CT metabolic and volumetric parameters in metastatic ALK plus NSCLC

ObjectiveThe aim of this study is to determine the role of metabolic and volumetric parameters obtained from 18Fluorine-Fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging on progression-free survival (PFS) and overall survival (OS) in patients with advanced nonsquamous cell lung carcinoma (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement.MethodsPre and post-treatment PET/CT images of the ALK + NSCLC patients between January 2015 and July 2020 were evaluated. The highest standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were obtained from pre-tyrosine kinase inhibitor (TKI) basal PET/CT (PETpre) and post-TKI PET/CT (PETpost) images. Total MTV (tMTV) and total TLG (tTLG) values were calculated by summing MTV and TLG values in all tumor foci. The change (Delta) in pSUVmax, pMTV, pTLG, tMTV and tTLG before and after treatment was calculated.The relationship of these parameters with OS and PFS was analyzed.ResultstTLG(pre), tMTV(pre), pTLG(pre), pMTV(pre), increment SUVmax, increment tMTV and increment tTLG values were found to be associated with OS; increment tMTV, increment tTLG, tTLG(pre), tMTV(pre), pTLG(pre) and pMTV(pre) were associated with PFS. The cutoff values in both predicting OS and PFS were calculated as -31.6 and 391.1 for increment tMTV and tTLG(pre), respectively. In Cox regression analysis, increment tMTV and stage for OS and increment tMTV and tTLGpre for PFS were obtained as prognostic factors.ConclusionsMetabolic and volumetric parameters, especially TLG values in the whole body before treatment and change in whole body MTV value, obtained from PET/CT may be useful in predicting prognosis and determining treatment strategies for patients with advanced ALK + NSCLC

The effect of helicobacter pylori eradication on macrophage migration inhibitory factor, c-reactive protein and fetuin-a levels

OBJECTIVES: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor and fetuin-A in patients with dyspepsia who are concurrently infected with H. pylori. METHODS: H.pylori infection was diagnosed based on the 14C urea breath test (UBT) and histology. Lansoprazole 30 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily were given to all infected patients for 14 days; 14C UBT was then re-measured. In 30 subjects, migration inhibitory factor, fetuin-A and hs-CRP levels were examined before and after the eradication of H. pylori infection and compared to levels in 30 healthy subjects who tested negative for H. pylori infection. RESULTS: Age and sex distribution were comparable between patients and controls. Migration inhibitory factor and hs-CRP levels were higher, and fetuin-A levels were lower, in H. pylori-infected patients (p<0.05). Following eradication of H. pylori, migration inhibitory factor and hs-CRP levels were significantly decreased, whereas fetuin-A levels were increased. However, eradication of the organism did not change lipid levels (p>0.05). CONCLUSION: These findings suggest that H. pylori eradication reduces the levels of pro-inflammatory cytokines such as migration inhibitory factor and hs-CRP and also results in a significant increase in anti-inflammatory markers such as fetuin-A

Neurological soft signs might be endophenotype candidates for patients with deficit syndrome schizophrenia

BACKGROUND: Schizophrenia is a chronic, disabling, disorder that affects approximately 1% of the population. The nature of schizophrenia is heterogeneous, and unsuccessful efforts to subtype this disorder have been made. Deficit syndrome schizophrenia (DS) is a clinical diagnosis that has not been placed in main diagnostic manuals. In this study, we aimed to investigate and compare neurological soft signs (NSS) in DS patients, non-deficit schizophrenia (NDS) patients, and healthy controls (HCs). We suggest that NSS might be an endophenotype candidate for DS patients. METHODS: Sixty-six patients with schizophrenia and 30 HCs were enrolled in accordance with our inclusion and exclusion criteria. The patients were sub-typed as DS (n=24) and NDS (n=42) according to the Schedule for the Deficit Syndrome. The three groups were compared in terms of sociodemographic and clinical variables and total scores and subscores on the Physical and Neurological Examination for Soft Signs (PANESS). Following the comparison, a regression analysis was performed for predictability of total PANESS score and its subscales in the diagnosis of DS and NDS. RESULTS: The groups were similar in terms of age, sex, and smoking status. The results of our study indicated that the total PANESS score was significantly higher in the DS group compared to the NDS and HC groups, and all PANESS subscales were significantly higher in the DS group than in the HC group. The diagnosis of DS was predicted significantly by total PANESS score (P<0.001, odds ratio =9.48, 95% confidence interval: 0.00–4.56); the synergy, graphesthesia, stereognosis, motor tasks, and ability to maintain posture subscales were found to be significant predictors. CONCLUSION: This study confirms that NSS were higher in patients with DS. In addition, we suggest that our results might support the notion of DS as a different and distinct type of schizophrenia. NSS might also be a promising candidate as an endophenotype for DS. However, large sampled, multicentric studies are needed to clarify the place of NSS as an endophenotype in DS

Social stigmatization in Turkish patients with chronic hepatitis B and C

Background and aim: Viral hepatitis is the most important cause of chronic hepatitis worldwide. Stigmatization is defined as a feeling of rejection and isolation of patients by society due to illness. There are no studies on chronic viral hepatitis in the literature in English, which has its own religious and socio-cultural structure. In our study, we aimed to investigate the presence of social stigmatism and psychosocial effects on patients with different stages of chronic viral hepatitis B and C. Methods: Forty-five patients with chronic hepatitis C and 114 patients with chronic hepatitis B were enrolled in the study. Berger’s scale was used for stigmatization, composed of 40 four-point Likert items that have four subscales: personalized stigma, disclosure, negative self-image, and public attitude. Stigma score ranges between one and four. Stigma is accepted as present if the overall score is above two. Results: Overall the mean stigma scores were 1.97 ± 0.58 and 2.14 ± 0.57 for chronic hepatitis B and C, respectively. There was stigma in 47.4% of the patients with chronic hepatitis B, and 60% of the patients with chronic hepatitis C. Being male was the risk factor on overall stigma, disclosure and public attitude in chronic hepatitis C. Living in an urban setting was the risk factor on negative self-image in chronic hepatitis C and on personalized stigma and disclosure in chronic hepatitis B

Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls. METHODS: After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23) and nondeficit syndrome (N=35) according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels. RESULTS: The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls. CONCLUSION: This study suggests that decreased BDNF levels may play a role in the pathophysiology of schizophrenic patients with deficit syndrome. Nonetheless, additional studies using a larger patient sample size are needed to investigate the serum BDNF levels in schizophrenic patients with deficit syndrome

Coexistence of cervico-thoracic extradural en-plaque meningioma with multiple intracranial meningiomas

Meningioma is one of the most common tumors in the spinal cord. Extradural and en-plaque variety of meningioma occur less frequently. A 47-year-old woman is presented with radiculopathy signs. Magnetic resonance imaging revealed a lesion from C6 through T3 vertebral levels compressing the cord both anteriorly and posteriorly. Subtotally excision was performed and histopathologic signs showed transitional type of meningioma (WHO Grade 1). Post operatively, she had good neurological recovery. Intraoperative findings point out that the en-plaque meningioma was pure extradural. Twelve cases of pure extradural en-plaque meningioma have been reported in the literature. Besides, to the best our knowledge coexistence of “en plaque” spinal epidural meningioma with meningiomas in cranial cavity has not been reported. Complete resection is mandatory to prevent recurrence. Moreover, it is considerably difficult to remove the parts of tumor over anterior of the dura without complication

Mean platelet volume is associated with disease severity in patients with obstructive sleep apnea syndrome

OBJECTIVE: Obstructive sleep apnea syndrome is associated with cardiovascular diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor of cardiovascular thromboembolic events. The aim of the present study is to investigate the association between the MPV and disease severity in patients with obstructive sleep apnea syndrome. METHODS: We prospectively included 194 obstructive sleep apnea syndrome patients without cardiovascular disease (mean age 56.5±12.5 years) who were undergoing sleep tests. An overnight full laboratory polisomnography examination was conducted on each patient. The patients were divided into 3 groups according to the apnea-hypopnea index (AHI): (1) AHIlow group: 5≤AH

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism:a single centre's experience

Objective: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. Design: Retrospective cohort study. Patients: PHPT assessed between 2006 and 2014 (n = 611) in a university hospital. Measurements: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. Results: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). Conclusions: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required

Isoflurane exposure in infant rats acutely increases aquaporin 4 and does not cause neurocognitive impairment

Isoflurane is commonly used in pediatric population, but its mechanism of action in cognition is unclear. Aquaporin 4 (AQP4) regulates water content in blood, brain, and cerebrospinal fluid. Various studies have provided evidence for the role of AQP4 in synaptic plasticity and neurocognition. In this study, we aimed to determine whether a prolonged exposure to isoflurane in infant rats is associated with cognition and what effect this exposure has on AQP4 expression. Ten-day-old [postnatal day (P) 10] Wistar albino rats were randomly allocated to isoflurane group (n = 32; 1.5% isoflurane in 50% oxygen for 6 hours) or control group (n = 32; only 50% oxygen for 6 hours). Acute (P11) and long-term (P33) effects of 6-hour anesthetic isoflurane exposure on AQP4 expression were analyzed in whole brains of P11 and P33 rats by RT-qPCR and Western blot. Spatial learning and memory were assessed on P28 to P33 days by Morris Water Maze (MWM) test. The analysis revealed that isoflurane increased acutely both mRNA (~4.5 fold) and protein (~90%) levels of AQP4 in P11 rats compared with control group. The increasing levels of AQP4 in P11 were not observed in P33 rats. Also, no statistically significant change between isoflurane and control groups was observed in the latency to find the platform during MWM training and probe trial. Our results indicate that a single exposure to isoflurane anesthesia does not influence cognition in infant rats. In this case, acutely increased AQP4 after isoflurane anesthesia may have a protective role in neurocognition