Evaluation of long-term function, complications, quality of life and health status after restorative proctocolectomy with ileo neo rectal and with ileal pouch anal anastomosis for ulcerative colitis.

AIM: Restorative surgery after (procto)colectomy with ileo-neorectal anastomosis (INRA) or restorative proctocolectomy with ileal pouch anal anastomosis (RPC) combines cure of ulcerative colitis (UC) with restoration of intestinal continuity. This study aimed to evaluate these two operations. METHOD: Patients having INRA and RPC were matched according to sex, age at onset of UC, age at restorative surgery and duration of follow-up. Patients were included if they were over 18 years of age, had UC confirmed histopathologically and had undergone either operation. Long-term function, anal and neorectal physiology, complications, quality of life (QoL) and health status (HS) were determined. RESULTS: Seventy-one consecutive patients underwent surgery with the intention of having an INRA procedure. This was successfully carried out in 50, and 21 underwent intra-operative conversion to RPC. Median defaecation frequency was 6/24 h. In 11/71 patients reservoir failure occurred and 13/71 developed pouchitis. QoL and HS were comparable to the healthy population. Median follow-up was 6.2 years. These patients were matched with 71 patients who underwent RPC. RPC was successful in all patients. Median defaecation frequency was 8/24 h. Failure occurred in 7/71 patients and 13/71 developed pouchitis. QoL and HS were comparable with the healthy population. Median follow-up was 6.9 years. CONCLUSION: Comparison of INRA and RPC on an intention to treat basis was not considered to be realistic due to the high intra-operative conversion rate and the failures in the INRA group. RPC remains the procedure of choice for restoring intestinal continuity after proctocolectomy for UC.

The ileo neo-rectal anastomosis in patients with familial adenomatous polyposis: a prospective case series with long-term follow up.

AIM: In patients with familial adenomatous polyposis (FAP), removal of the colonic mucosa is essential to reduce the lifetime risk of developing cancer). For this purpose, ileo-pouch anal anastomosis (IPAA) has been the gold standard, but morbidity related to the dissection of the pelvis remains substantial. In an attempt to reduce the procedure-related complications of pelvic dissection, ileoneo-rectal anastomosis (INRA) has been developed. In this case series of FAP patients, the long-term functional results, morbidity and quality of life (QoL) of the INRA procedure were evaluated and compared with its early outcome. METHOD: Long-term follow up of a consecutive group of eight FAP patients with an INRA procedure (between 1998 and 2005) was undertaken. Data on functional results, complications, manometry and endoscopy were recorded prospectively. RESULTS: Eight patients with FAP underwent the INRA procedure. The median number of defaecations over 24 h was five. No pelvic sepsis or bladder dysfunction occurred. One patient, in whom concomitant Crohn's disease was diagnosed in retrospect, was converted to IPAA. In the INRA patients, no sexual dysfunction occurred. Endoscopic examination showed normal mucosa without any evidence of polyp formation. CONCLUSION: Restorative surgery by means of the INRA procedure yields good functional results in FAP patients, without any pelvic dissection-related morbidity or regrowth of polyps in the neo-rectum.

Quality of life, health-related quality of life and health status in patients having restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis: a systematic review.

AIM: There are numerous studies on quality of life (QoL), health-related quality of life (HRQoL), and health status (HS) in patients undergoing surgery for ulcerative colitis. A systematic review of published literature was conducted to establish the quality of these studies and to determine QoL, HRQoL, and HS in patients after ileal pouch-anal anastomosis for ulcerative colitis. METHOD: All published studies describing QoL, HRQoL, and HS in adult patients in combination with ileal pouch-anal anastomosis for ulcerative colitis were reviewed systematically. No time or language limitations were applied. Relevance was established on the basis of three pre-specified selection criteria: 1) ileal pouch-anal anastomosis was performed for ulcerative colitis, 2) QoL, HRQoL, and HS were reported as outcome of the study and 3) studies reported a minimum follow-up after surgery for 12 months. Outcome variables were results of QoL, HRQoL, and HS, characteristics of the study population, pouch construction, duration of follow-up, and time of assessment in months before and after restorative surgery. Descriptive data synthesis was performed by tabulation displaying the methodological quality, study characteristics and conclusions on QoL, HRQoL, and HS measurements in the studies. RESULTS: The review included 33 studies comprising 4790 patients. Three were graded to be of high quality, 23 of moderate quality and seven of low quality. All reported improved HS and the majority reported improved HRQoL. However, none of the studies reported on QoL. CONCLUSION: The HRQoL and HS of patients with ulcerative colitis improved 12 months after restorative proctocolectomy with an ileal pouch-anal anastomosis and were indistinguishable from the HRQoL and HS of the normal healthy population.

Quality of life and health status before and after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is considered the surgical treatment of choice for patients with ulcerative colitis. Quality of life (QoL) and health status are the most important patient-related outcomes. Studies investigating QoL are often cross-sectional and focus on health status. This longitudinal study evaluated QoL and health status after IPAA for ulcerative colitis and compared these with reference data from a healthy population. METHODS: Patients with ulcerative colitis who underwent a pouch operation between 2003 and 2008 completed validated questionnaires for QoL and health status. Questionnaires were completed before pouch surgery, and 6, 12, 24 and 36 months after operation. The effect of IPAA on QoL and health status was analysed, and data were compared with reference values from the healthy Dutch population. RESULTS: Data were obtained for 30 of the 32 patients. Six months after IPAA, QoL was at least comparable with that of the reference population in four of six domains. Twelve months after IPAA, overall QoL had improved, supported by findings in three QoL domains. Six months after IPAA, health status was comparable to that of the reference population in three of eight dimensions, and after 3 years it was at least comparable in five dimensions. CONCLUSION: QoL and health status increased after IPAA and reached levels comparable with those of the healthy reference population in a majority of domains and dimensions. QoL was restored first after IPAA, followed by health status.

Saphenous vein spiral graft: successful emergency repair of a mycotic aneurysm with aortoduodenal fistula.

Mycotic aneurysms leading to aortoduodenal fistula (ADF) are associated with high morbidity and mortality. We report a patient with a mycotic aneurysm and ADF who required emergency laparotomy. After excision of the aneurysm, vascular reconstruction was performed using an autologous graft. The left long saphenous vein was harvested and constructed into a spiral graft. The graft was inserted using a standard inlay technique. After 12 months the patient is in good health. No inflammation or dilation of the saphenous vein spiral graft has been noted. We suggest that in the emergency treatment of mycotic abdominal aneurysm, aortic reconstruction with saphenous vein spiral graft is a valuable option.

Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood.

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

Metformin and lactic acidosis: cause or coincidence? A review of case reports.

OBJECTIVE: Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis. DESIGN: A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Express (1966-99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin-induced lactic acidosis (MILA) were cross-referenced. SUBJECTS: Cases were included for analysis if they met the following criteria: serum pH < or =7.35, lactate concentration > or =5 mmol L(-1). INTERVENTION: A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2). MAIN OUTCOME MEASURES: Statistical analysis included the paired interobserver agreement (kappa) and multivariate regression analysis. RESULTS: Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2-10). The kappa-value was 0.041 (SD = 0.24, range -0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations. CONCLUSIONS: Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered.

Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease.

BACKGROUND: Cranial irradiation for children with brain tumors frequently leads to neuroendocrine deficiencies. In this controlled study, the authors investigated risk factors for cardiovascular disease (CVD) for long term survivors of childhood brain cancer. They also tested whether the presence of these risk factors was related to endocrine status. METHODS: In 26 survivors of childhood brain cancer (mean age, 25.8 years; mean posttreatment interval, 16 years) and 29 healthy controls (mean age, 27.7 years), the blood pressure, smoking habits, body mass index (BMI), and waist/hip (W/H) ratio were determined. Lipids and lipoproteins were measured and endocrine function was assessed. Carotid intima-media thickness (IMT) measurements were performed by high resolution ultrasonography. RESULTS: In the survivors of childhood brain cancer, systolic blood pressure and W/H ratio were elevated compared with controls. The cholesterol/high density lipoprotein ratio (4.7 +/- 1.7 vs. 3.4 +/- 0.8 mmol/L, P = 0.0005), low density lipoprotein cholesterol level (3.3 +/- 0.9 vs. 2.8 +/- 0.6 mmol/L, P = 0.027), and apolipoprotein B level (P = 0.001) were higher in survivors of childhood brain cancer, whereas HDL cholesterol was lower (P = 0.005). The IMT was increased in the survivor group, but only in the carotid bulb (0.63 mm +/- 1.6 vs. 0.53 mm +/- 1.1, P = 0.02), not in the internal or common carotid artery. In the absolute growth hormone deficient (GHD) population (n = 9), LDL cholesterol and apolipoprotein B levels were elevated and the W/H ratio was particularly increased compared with the other survivors of childhood brain cancer. CONCLUSIONS: For long term survivors of brain cancer, the risk for CVD is strongly increased due to dyslipidemia, central obesity, and elevated systolic blood pressure, particularly for those with GHD. The first effects of this increased risk for CVD were observed in the carotic bulb, as assessed by IMT measurements. Efforts should be directed at CVD prevention by risk factor control.

Effect of metformin on glycaemic control in type 2 diabetes in daily practice: a retrospective study.

INTRODUCTION: Recently the UKPDS study revealed the potency of metformin therapy in obese type 2 diabetic patients. A retrospective study was performed to assess the efficacy of metformin therapy in improving metabolic control in everyday practice. PATIENTS AND METHODS: Type 2 diabetic patients were included if they met the following criteria: metformin had been added when the previous treatment failed to optimise glycaemic control expressed in HbA1c level; duration of metformin therapy had to be at least six months. Efficacy of metformin therapy, expressed as a decrease in HbA1c, was measured with a median follow-up of 32 (range 6-60) months. Variables were analysed using a paired t-test. RESULTS: One hundred and sixty-three patients were treated with metformin. 98 patients were excluded, because of absence of an HbA1c value prior to treatment with metformin mainly (n = 78). The mean HbA1c of included patients had decreased 1.4% (p < 0.001) after 6 months (n = 65), 1.6% (p < 0.001) after 24 months (n = 45) and 1.5 (p < 0.001) after 36 months (n = 28). During follow-up there was no significant weight gain or loss. CONCLUSION: Metformin can be considered an effective treatment to improve glycaemic control in obese type 2 diabetic patients.

Are clinical parameters valuable prognostic factors in childhood primitive neuroectodermal tumors? A multivariate analysis of 105 cases.

BACKGROUND: Medulloblastoma is one of the most frequent brain tumors in children. Long-term survivors are often confronted with serious late sequelae, caused by the therapy. Therefore, prognostic markers must be identified that allow the children to be assigned to different treatment schedules according to their predicted outcome. PATIENTS AND METHODS: The medical data of 110 children with a medulloblastoma or central primitive neuroectodermal tumor (PNET), that were admitted to the Emma Kinderziekenhuis in Amsterdam were analyzed by univariate and multivariate analyses. RESULTS: In univariate analysis the following characteristics had a significant influence on progression free survival (PFS): (a) presence of meningeal metastases at the time of diagnosis, (b) presence of tumor cells in the cerebrospinal fluid before or after surgery, (c) extent of resection, (d) necessity for permanent cerebrospinal fluid (CSF) shunting and (e) radiation dose to the posterior fossa. On multivariate analysis only the presence of metastases and the radiation dose to the posterior fossa retained significance. CONCLUSION: At the time of diagnosis, no reliable clinical prognostic markers are available for the majority of patients. Further molecular studies must be undertaken to identify such prognostic factors.

[Late sequelae of oncologic treatment in children]. / Late gevolgen van oncologische behandeling bij kinderen.

The risk of late effects of cancer treatment in children is higher than that after treatment during adulthood. The late effects of chemotherapy are proportional to the dosage and those of irradiation to the size of the radiation field, fractionation and dose. Irradiation may lead to impaired growth of bone and soft tissues, cranial irradiation to pituitary deficiencies, alopecia and impaired cognitive function, irradiation of the neck to altered thyroid function, thoracic irradiation to diminished pulmonary function and cardiovascular morbidity, radiation therapy of the abdomen to infertility in females, impaired renal function and chronic enteritis. Chemotherapy-induced damage is more organ-specific. Well-known cardiotoxic agents are the anthracycline derivatives. Restricted pulmonary function is seen after treatment with bleomycin and nitrourea derivatives. Several antineoplastic agents are gonadotoxic in men. Nephrotoxic agents are cisplatin and ifosfamide. The cumulative relative risk of developing a second primary neoplasm is 3,8-6,9 after a follow-up period of 25 years. Alkylating agents and the topoisomerase inhibitors are known to increase the risk of haematologic malignancy, while radiation therapy is associated with bone, soft tissue, thyroid, breast, brain and gastrointestinal malignancies.

Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma.

The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25 years (median 16 years) after therapy. The radiation dose to the whole cranium and spinal axis was 35 +/- 2.6 Gray (mean +/- standard deviation) with a boost to the posterior fossa of 18 +/- 3.7 Gray. 13 subjects had received additional chemotherapy. In 15 of 20 (75%) subjects, endocrine abnormalities were observed. In 14 (70%), growth hormone (GH) secretion was impaired; 7 (35%) subjects had an absolute GH deficiency, while 7 (35%) showed subnormal responses to insulin-induced hypoglycaemia. In contrast, only 20% (4) of these subjects showed impairment of the hypothalamus-pituitary-thyroid (HPT) axis, while 15% (3) showed central impairment of hypothalamus-pituitary-gonadal (HPG) function. Central impairment of the HPG axis was associated with impaired GH secretion in all cases. Central adrenal insufficiency was not observed. Basal levels of prolactin were normal in all subjects. Young age at treatment was a determinant of GH deficiency in adulthood (P = 0.014). Neither post-treatment interval, nor the use of chemotherapy were determinants of central endocrine impairment in adulthood. In long-term survivors of medulloblastoma, GH deficiency has a high prevalence. In contrast, impairment of the HPG and HPT axis is less common, while central adrenal insufficiency was not observed.

Irreversible gonadal damage in male survivors of pediatric Hodgkin's disease.

BACKGROUND: Gonadal damage in adult patients after chemotherapy for Hodgkin's disease is well documented, but data of patients treated before adulthood are scarce. METHODS: Gonadal and hormonal function were studied in 19 male long term survivors of Hodgkin's disease who were treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP chemotherapy) before (n = 15) or during puberty (n = 4). The studies were performed a median of 10 years after treatment and repeated in the majority of the patients at the time of yearly visits. RESULTS: Germ cell damage was present in all patients. Semen analysis revealed azoospermia in 12 patients and oligospermia in 6; no recovery of spermatogenesis was seen at follow-up. Testicular size was small in all but one patient. Follicle-stimulating hormone levels were elevated (mean, 14.4 +/- 7.8 U/l) and increased over time (mean, 21.1 +/- 10.5 U/l, P < 0.001). In seven patients, luteinizing hormone (LH) was elevated, indicating Leydig cell dysfunction; also in four of those patients, plasma testosterone was decreased. In three other patients, the response of LH to gonadotropin-releasing hormone was exaggerated with a normal basal LH and testosterone. Comparing testicular function of prepubescent versus pubescent state at time of treatment appears to show a trend for improved outcome in the younger patients. CONCLUSIONS: Gonadal function of long term survivors of pediatric Hodgkin's disease treated with MOPP chemotherapy is severely impaired permanently.

99mTc-CD19 monoclonal antibody is not useful for imaging of B cell non-Hodgkin's lymphoma.

In this study we investigated the applicability of 99mTc-labeled CD19 monoclonal antibody (mAb) for tumor imaging in patients with B cell non-Hodgkin's lymphoma. A 1-mg sample of murine CD19 mAb was labeled with approximately 550 MBq [99mTc]pertechnetate. The labeled mAb was administered i.v. to seven patients, four without and three with pretreatment with 10 mg unlabeled CD19 mAb. The number of circulating B cells was decreased by 44 +/- 5% 1 h after injection of the radiolabeled mAb. Peripheral B cells were coated with CD19, resulting in partial modulation of CD19, most pronounced in the three pretreated patients. Whole-body images were obtained with a gamma camera and compared with results obtained by conventional imaging techniques. Initially, blood-pool activity dominated, whereas 24 h after injection the radioactivity was mainly located in the spleen, kidneys and liver. In two patients, a lesion in the spleen appeared as an unlabeled spot. In one patient, a lesion in the femur, which was detected by computed tomography (CT) and gallium-67 scans, was also seen on the CD19 scan from 1 h after administration of the radioimmunoconjugate onwards. Good imaging of bone marrow infiltration was observed in one of three patients. Lymph node involvement was not observed in any of the patients in whom affected lymph nodes were detected by CT or gallium-67 scan. In conclusion, in the present study radioimmunodetection with 99mTc-labeled CD19 mAb was found to be inferior to CT and gallium-67 scanning in the diagnosis of patients with B cell non-Hodgkin's lymphoma.

Liquorice-induced hypertension--a new understanding of an old disease: case report and brief review.

The case is described of a 40-year-old female with severe hypertension and hypokalaemic metabolic alkalosis, due to prolonged liquorice ingestion. The pseudo-aldosterone-like effects of liquorice have always been attributed to glycyrrhizic acid, but its biochemical substrate has remained elusive. It is now known that glycyrrhetenic acid, the hydrolytic metabolite of glycerrhizic acid, is the active component of liquorice which causes inhibition of the peripheral metabolism of cortisol. Cortisol binds with the same affinity as aldosterone to the mineralocorticoid receptor resulting in a hypermineralocorticoid condition. Ingestion of liquorice may therefore result in retention of sodium and water, hypertension, hypokalaemia, alkalosis and suppression of the renin-aldosterone system. The literature on liquorice-induced hypertension is briefly reviewed with emphasis on the biochemical features of this mineralocorticoid excess syndrome.

Kikuchi's lymphadenitis: report of a Yersinia enterocolitica-associated case and an overview of aetiology and clinical outcome.

Kikuchi's lymphadenitis (KL; histiocytic necrotizing lymphadenitis without granulocytic infiltration) is a generally benign, febrile disorder of unknown aetiology with distinct histological features. To date, a minority of cases reported have been associated with infectious agents. A typical pathological case of KL is described where involvement of Yersinia enterocolitica was shown by an indirect immunofluorescent assay applied to lymphatic tissue. The case is discussed with emphasis on recent insight into the course and aetiology of KL.

[Progressive multifocal leukoencephalopathy in a female patient with chronic lymphatic leukemia]. / Progressieve multifocale leuko-encefalopathie bij een patiënte met chronische lymfatische leukemie.

This case report describes a 78-year old female patient with chronic lymphocytic leukaemia and neurological symptoms due to progressive multifocal leukoencephalopathy (PML). At autopsy the histopathology was characteristic, the involvement of JC virus was established. PML occurs in immunocompromised patients and is caused by infection with JC papova virus. Epidemiology, clinical course, diagnostic procedures with special reference to the use of the polymerase chain reaction, and therapy are briefly reviewed.