Intrahepatic cholestasis of pregnancy:When should you look further?

Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.

Management of recurrent rectal cancer:A population based study in greater Amsterdam

AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.

Childhood constipation as an emerging public health problem

Functional constipation(FC) is a significant health problem in children and contrary to common belief, has serious ramifications on the lives of children and their families. It is defined by the Rome criteria which encourage the use of multiple clinical features for diagnosis. FC in children has a high prevalence(0.7%-29%) worldwide, both in developed and developing countries. Biopsychosocial risk factors such as psychological stress, poor dietary habits, obesity and child maltreatment are commonly identified predisposing factors for FC. FC poses a significant healthcare burden on the already overstretched health budgets of many countries in terms of out-patient care, in-patient care, expenditure for investigations and prescriptions. Complications are common and range from minor psychological disturbances, to lower health-related quality of life. FC in children also has a significant impact on families. Many paediatric clinical trials have poor methodological quality, and drugs proved to be useful in adults, are not effective in relieving symptoms in children. A significant proportion of inadequately treated children have similar symptoms as adults. These factors show that constipation is an increasing public health problem across the world with a significant medical, social and economic impact. This article highlights the potential public health impact of FC and the possibility of overcoming this problem by concentrating on modifiable risk factors rather than expending resources on high cost investigations and therapeutic modalities.

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with MAFLD.METHODS Consecutive patients with histologically confirmed MAFLD were included.The discrimination ability of different non-invasive scores was compared.RESULTS A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,respectively.The area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically significant.The best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.CONCLUSION APRI and BARD scores do not perform well in MAFLD.The FIB-4 and NFS could be more useful,but a new threshold is needed.Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Systematic review: The placebo effect of psychological interventions in the treatment of irritable bowel syndrome

AIM To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS Randomized controlled trials comparing psychological interventions(stress management/relaxation therapy(cognitive) behavioral therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of adult patients with irritable bowel syndrome(IBS) diagnosed with the Manning or Rome criteria with an adequate placebo control treatment and reporting data on IBS symptom severity were identified by searching Pub Med, Embase, the Cochrane Library, CINAHL and Psyc INFO databases. Full-text articles that were written in English and published between 1966 and February 2016 in peer-reviewed journals were selected for the present review. Placebo interventions were considered to be adequate if the number of sessions and the amount of time spent with the therapist were the same as in the active treatment. The placebo response rate(PRR) was computed for IBS symptom severity(primary outcome measure) as well as for anxiety, depression and quality of life(secondary outcome measures). RESULTS Six studies, with a total of 555 patients met the inclusion criteria. Four studies used an educational intervention, whereas two studies used a form of supportive therapy as the placebo intervention. The PRR for IBS symptom severity ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for depression 20% to 125% for quality of life. The PRR associated with pharmacological treatments, treatment with dietary bran and complementary medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in studies on psychological interventions was comparable to that in studies on pharmacological, dietary and alternative medical interventions.CONCLUSION The PRR is probably determined to a larger extent by patient-related factors, such as expectations and desire for the treatment to be effective, than the content of the placebo intervention.

Drug-induced autoimmune hepatitis:A minireview

Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH.

Gastroenterostoma after Billroth antrectomy as a premalignant condition

Gastric stump carcinoma （GSC） following remote gastric surgery is widely recognized as a separate entity within the group of various types of gastric cancer. Gastrecto- my is a well established risk factor for the development of GSC at a long time after the initial surgery. Both exo- as well as endogenous factors appear to be involved in the etiopathogenesis of GSC, such as achlorhydria, hypergastrinemia and biliary reflux, Epstein-Barr virus and Helicobacter pylori infection, atrophic gastritis, and also some polymorphisms in interleukin-l~ and maybe cyclo-oxygenase-2. This review summarizes the litera- ture of GSC, with special reference to reliable early di- agnostics. In particular, dysplasia can be considered as a dependable morphological marker. Therefore, close endoscopic surveillance with multiple biopsies of the gastroenterostomy is recommended. Screening start- ing at 15 years after the initial ulcer surgery can detect tumors at a curable stage. This approach can be ofspecial interest in Eastern European countries, where surgery for benign gastroduodenal ulcers has remained a practice for a much longer time than in Western Eu- rope, and therefore GSC is found with higher frequency.

Early-onset gastric cancer:Learning lessons from the young

There is by no means a clear-cut pattern of mutations contributing to gastric cancers,and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer,such as Helicobacter pylori infection,diet,ageing and other environmental factors.Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship.It is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOGC) than in gastric cancers found in older patients as they have less exposure to environmental carcinogens.EOGC,therefore,could provide a key to unravelling the genetic changes in gastric carcinogenesis.Gastric cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric carcinogenesis.This review summarizes the literature regarding EOGC and also presents evidence that these cancers have a unique molecular-genetic phenotype,distinct from conventional gastric cancer.

Differentiation of malignant and benign proximal bile duct strictures: The diagnostic dilemma

AIM: To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These fi ndings were analyzed to obtain the fi nal diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group Ⅰ) whereas 10 patients (15%, groupⅡ) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group Ⅰvs 60% group Ⅱ P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group Ⅰcompared to group Ⅱ The various imaging modalities showed vascular involvement exclusively in the malignant group (36%,P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group Ⅰ whereas none in group Ⅱ showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.

Autoimmune gastritis presenting as iron deficiency anemia in childhood

AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.

Colonoscopic yield of colorectal neoplasia in daily clinical practice

AIM:To assess the prevalence and location of ad-vanced neoplasia in patients undergoing colonoscopy,and to compare the yield per indication.METHODS:In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterdam area (Northern Holland),data of all colonoscopies performed during a three month period in 2005 were analyzed. The location and the histological features of all colonic neoplasia were recorded. The prevalence and the distribution ofadvanced colorectal neoplasia and differences in yield between indication clusters were evaluated. Advanced neoplasm was defi ned as adenoma > 10 mm in size,with > 25% villous features or with high-grade dyspla-sia or cancer.RESULTS:A total of 4623 eligible patients underwent a total colonoscopy. The prevalence of advanced neo-plasia was 13%,with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas. Sixty-seven percent and 33% of advanced neoplasia were located in the distal and proximal colon,respectively. Of all patients with right-sided advanced neoplasia (n = 228),51% had a normal distal colon,whereas 27% had a syn-chronous distal adenoma. Ten percent of all colono-scopies were performed in asymptomatic patients,7% of whom had advanced neoplasia. In the respective procedure indication clusters,the prevalence of right-sided advanced neoplasia ranged from 11%-57%. CONCLUSION:One out of every 7-8 colonoscopies yielded an advanced colorectal neoplasm. Colonoscopy is warranted for the evaluation of both symptomatic and asymptomatic patients.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

Bile leakage after loop closure vs clip closure of the cystic duct during laparoscopic cholecystectomy:A retrospective analysis of a prospective cohort

BACKGROUND Laparoscopic cholecystectomy(LC)is one of the most frequently performed surgical procedures.Cystic stump leakage is an underestimated,potentially life threatening complication that occurs in 1%-6%of the patients.With a secure cystic duct occlusion technique during LC,bile leakage becomes a preventable complication.AIM To investigate the effect of polydioxanone(PDS)loop closure of the cystic duct on bile leakage rate in LC patients.METHODS In this retrospective analysis of a prospective cohort,the effect of PDS loop closure of the cystic duct on bile leakage complication was compared to patients with conventional clip closure.Logistic regression analysis was used to develop a risk score to identify bile leakage risk.Leakage rate was assessed for categories of patients with increasing levels of bile leakage risk.RESULTS Of the 4359 patients who underwent LC,136(3%)underwent cystic duct closure by a PDS loop.Preoperatively,loop closure patients had significantly more complicated biliary disease compared to the clipped closure patients.In the loop closure cohort,zero(0%)bile leakage occurred compared to 59 of 4223(1.4%)clip closure patients.For patients at increased bile leakage risk(risk score≥1)rates were 1.6%and up to 13%(4/30)for clip closure patients with a risk score≥4.This risk increase paralleled a stepwise increase of actual bile leakage complication for clip closure patients,which was not observed for loop closure patients.CONCLUSION Cystic duct closure with a PDS loop during LC may reduce bile leakage in patients at increased risk for bile leakage.

Application of correlation techniques in the analysis of corpus cavernosum electromyographic signals

Aim： To establish an objective, easy-to-use and comprehensive method to analyze corpus cavernosum electromyo- graphic signals （CC-potentials）. Methods： CC-potentials were recorded during flaccidity in 23 young healthy volunteers, with surface electrodes placed on the penile shaft bilaterally. Based on the correlation function of Matlab software, an application program for the analysis of CC-potentials was developed. Individual CC-potentials and their autocorrelation function were evaluated, yielding parameters amplitude （A）, duration （D）, and dominant frequency （DF）. The crosscorrelation function of both longitudinal and bilateral pairs of adjacent electrodes was calculated to assess the similar- ity and mutual delay of CC-potentials recorded simultaneously from different parts of the CC. The parameters derived were squared maximum cross-correlation coefficient （Rmax） and delay （τ）. Based on the absolute value of τ and the corresponding inter-electrode distance, propagation velocity （PV） was calculated. Results. The values of the parameters were determined automatically. No significant difference related to the locations of the electrodes for parameters A, D, and DF was detected. The cross-correlation showed that both longitudinal and bilateral CC-potential pairs had highly similar waveforms （the absolute values of Rmax were 0.80 ± 0.05 and 0.87 ± 0.06, respectively）. PV of longitudinal pairs was estimated as 6.15 ± 3.98 cm/s. Conclusion： The application program for correlation analysis of CC-potentials is a comprehensive and versatile method to analyze corpus cavernosum electromyographic recordings. Its objectiveness makes multi-center application possible.

Juvenile polyposis syndrome

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically,juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum,juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis.In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found.Both genes play a role in the BMP/TGF-beta signalling pathway.It has been suggested that cancer in juvenile polyposis may develop through the socalled "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma.Recognition of this rare disorder is important for patients and their families with regard to treatment,follow-up and screening of at risk individuals.Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome.In addition,juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer.This review discusses clinical manifestations,genetics,pathogenesis and management of juvenile polyposis syndrome.

Biliary drainage of the common bile duct with an enteral metal stent

In this case report we present an elderly patient who was referred to our hospital with recurrent episodes of cholangitis that persisted after placement of fi ve metal stents for a distal common bile duct(CBD) stenosis.All metal stents were endoscopically removed from the CBD by forceps after balloon dilatation of the papilla.A profoundly dilated CBD with sludge and concrements was seen.To ensure adequate bile drainage an enteral metal stent was inserted in the CBD.This case shows that proximally migrated uncovered metal stents in the CBD can be safely removed endoscopically under certain circumstances.We suggest that in the case of a CBD drainage problem due to an extremely dilated CBD,placement of an enteral metal stent in the CBD could be considered,especially in patients who are unfi t for surgery.

Giant cell arteritis: Current treatment and management

Glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers(C-reactive protein and erythrocyte sedimentation rate). Imaging techniques(e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with largevessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.

Femoroacetabular offset restoration in total hip arthroplasty;Digital templating a short stem vs a conventional stem

BACKGROUND Failure in restoring individual anatomy could be a reason for persistent functional limitations post total hip arthroplasty.Femoroacetabular offset(FAO)plays an important role in anatomic restoration,as loss of offset≥5 mm is associated with altered gait and decreased functional outcome.Preoperative assessment by use of digital templating has shown to be a reliable method for sizing the components in total hip arthroplasty,and can show if anatomic restoration is achieved.In recent years,short stems are growing in popularity as it could allow better restoration due to more variety in placement.AIM To assess whether restoration of the FAO differs between a short or a conventional stem by use of digital templating.Additionally,association of the preoperative offset and caput-colllum-diaphyseal angle(CCD-angle)within restoration of both stems was investigated,and the reliability of measurements was assessed.METHODS A total of 100 standardized hip radiographs were used for digital templating.Restoration of FAO was classified into“restored”or“not restored”,when a<5 mm or≥5 mm difference from baseline value presented,respectively.Differences between the two stems concerning proportions of correct restoration of the FAO were analyzed by use of McNemar tests.To assess association between CCDangle and preoperative FAO with absolute FAO restoration,multi-level analysis was performed by use of a linear mixed model to account for paired measurements.Through determination of the optimal point under the curve in operating curve-analysis,bootstrapping of thousand sets was performed to determine the optimal cutoff point of the preoperative FAO for restoration within the limits of 5 mm.Three observers participated for inter-observer reliability,with two observers measuring the radiographs twice for intra-observer reliability.RESULTS The mean preoperative FAO was 79.7 mm(range 62.5-113 mm),with a mean CCD-angle of 128.6°(range 114.5°-145°).The conventional stem could only restore the FAO in 72 of the cases,whereas the short stem restored the FAO in all cases.CCD-angle was not a predictor,but the preoperative FAO was.A cut-off point of 81.25 mm(95%confidence interval of 80.75-84.75 mm)in preoperative FAO was found where the conventional stem was unable to restore the FAO.Reliability of measurements was excellent,with an intra-observer reliability of 0.99 and inter-observer reliability in baseline measurements higher than 0.9 between the three observers.CONCLUSION In preoperative planning of FAO restoration in total hip arthroplasty,digital templating shows that short stems with a curve following the medial calcar are potentially better at restoring the FAO compared to conventional stems if the preoperative offset is≥80.0 mm.

Ethanol Lock Therapy as additional treatment of catheter-related bloodstream infections in pediatric patients receiving home parenteral nutrition

Background: Catheter related bloodstream infections (CRIs) are a major cause of morbidity, mortality and prolonged hospitalization in pediatric patients with home parenteral nutrition (HPN). In recent years, new prophylactic and treatment options have been evaluated to reduce the incidence of CRIs and infection related catheter removals. In children, two retrospective studies have shown the efficacy of ethanol lock treatment (ELT) in reducing the incidence of CRIs in pediatric oncology patients. However, prospective data are missing. Our aim of the present study was to evaluate prospectively the effect of ELT on the cure and recurrence rate of CRIs, duration of hospitalization and antibiotic use in HPN pediatric patients. Methods: HPN children older than three months with a clinical suspicion of a CRI were included and randomised to ELT or standard flushing treatment (heparin or taurolidine). The primary outcomes were persistence and recurrence of the bacteraemia and Central Venous Access Device (CVAD) removal. Secondary outcomes included duration of antibiotic use, duration of hospitalization and side effects. Results: Data from eight HPN children experiencing 14 suspected CRI were analysed. Seven patients had proven CRIs by positive blood cultures. Four were treated with ELT and three with their standard flushing treatment. One CRI persisted in the control group. In one single patient, bacteraemia recurred three times within 24 weeks. This patient had been enrolled in both study arms. A CVAD removal was needed in one patient because of occlusion. Conclusions: This small study showed no additional efficacy of the use of ELT on cure rate or recurrences of CRIs compared to standard therapy in HPN treated children. There were also no differences in duration of hospitalization, the use of antibiotics or CVAD removal between both groups.

Predictive Potential of FDG-PET/CT for Histological Transformation in Patients with Indolent Lymphoma

Backgrounds and Purpose—In indolent non-Hodgkin lymphoma, histological transformation is a dramatic event which reduces the prognosis significantly. SUVmax values from FDG-PET/CT help differentiate between aggressive and indolent lymphomas, and transformed indolent lymphomas also show an increased FDG uptake. Possibly FDG uptake increases early in the clinical course and could predict histological transformation. Our objective was to predict histological transformation in indolent lymphomas from initial staging FDG-PET/CT. Patients and Methods—A retrospective study was performed. Patients with biopsy-proven indolent lymphoma who had had initial staging FDG-PET/CT were included. Qualitative (foci compared with FDG uptake liver) and semiquantitative (SUVmax-value per focus) analyses were performed of all abnormal foci. Patient characteristics and outcome were evaluated. Results—We included 88 patients, 5 of whom developed a histological transformation. Semiquantitative analysis showed a relation between maximum standardized uptake value and histological transformation (odds ratio 1.25, 95% CI 1.024 - 1.513). Qualitative analysis showed a negative predictive relation of FDG uptake less than or equal to liver in the occurrence of histological transformation. Transformation-free survival was 100% over 30 months in those with FDG uptake lower than or equal to liver. More FDG uptake than liver showed transformation-free survival of 88% over 30 months. Conclusion—Qualitative analysis of staging FDG-PET/CT in indolent lymphomas could be useful to rule out transformation in the next 30 months. In our study, semiquantitative analysis was statistically significantly associated with histological transformation and maximum standardized uptake value. However, because of the small number of patients, cautious interpretation of the results is warranted. More studies are needed to investigate the role of staging PET/CT in patient with indolent non-Hodkin lymphoma in the prediction of transformation.