A retrospective cohort study of intra-corporeal versus extra-corporeal anastomosis for right hemicolectomy with cost-effectiveness analysis.

BACKGROUND: We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. METHODS: Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. RESULTS: A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. CONCLUSION: ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.

Seizure-related complication rate in a residential population with epilepsy and intellectual disability (ECOMRAID-trial).

INTRODUCTION: The aim of the ECOMRAID trial (Epileptic seizure related Complication RAte in residential population of persons with epilepsy and Intellectual Disability) was to study seizure-related complications (status epilepticus, respiratory complications, or other severe complications) in people with epilepsy and intellectual disability living in a residential setting. The results of the present study are a prerequisite for performing a prospective study into the effectiveness of nocturnal surveillance patients with high risk for Sudden unexpected death in epilepsy (SUDEP). MATERIAL AND METHODS: A retrospective study was conducted in three general residential care institutions and one residential specialized epilepsy clinic. In this 5-year cohort, we collected the following data: age (at inclusion and in case of death), sex, type of residential care, different types of complications, rescue/emergency medication administration, transfers to another department (internal midcare / monitoring unit or general hospital) and a self-designed SUDEP risk score. Our primary research questions were to assess the number of patients who experienced seizure-related complications and their individual complication rates. The secondary research questions were to document the relationship of these complications with the SUDEP risk score, with the type of residential living, and with the frequency of interventions by caregivers. RESULTS: We included 370 patients (1790 patient-years) and in 135 of them, we found 717 seizure-related complications. The following complication rates were found: all complications: at 36%, status epilepticus: at 13%, respiratory complications: at 5%, and other complications at 26%. In residential care institutions, we found fewer patients with complications compared to the specialized epilepsy clinic (all complications 24% vs 42%, OR 0.44, p < 0.01; status epilepticus 5% vs 17%, OR 0.27, p < 0.01; other: complications 19% vs 30%, OR 0.56, p < 0.05). In residential care institutions, we found more "other complications" than in the specialized epilepsy clinic (89% vs 71%, OR 3.13, p < 0.0001). The annual frequency of all complications together was higher in residential care institutions (range 0 to 21 vs 0 to 10, p < 0.05). Rescue medication was given to 75% of the patients, but more often in the specialized epilepsy clinic (median 2.6 vs 0.5 times/patient/year, p < 0.001). In the specialized epilepsy clinic, more patients were transferred to a midcare / monitoring unit or general hospital (56% vs 9%, OR 13.44, p < 0.0001) with higher yearly frequencies (median 0.2 vs 0.0, p < 0.001). There were no reported cases of SUDEP. The median SUDEP risk score was higher in the specialized epilepsy clinic (5 vs 4, p < 0.05) and was weakly correlated with the status epilepticus (ρ = 0.20, p < 0.001) and (total) complication rate (ρ = 0.18, p < 0.001). CONCLUSION: We found seizure-related complications in more than one-third of the patients with epilepsy and intellectual disability living in a residential setting over a period of 5 years. The data also quantify seizure-related complications in patients with epilepsy and intellectual disability.

Transanal total mesorectal excision and delayed coloanal anastomosis without stoma for low rectal cancer.

The management of low rectal cancer is a perennial challenge for colorectal surgeons. The benefits of transanal total mesorectal excision (TaTME) in low rectal cancer are to secure the distal margin and avoid surgical space constraints within the deep pelvis. However, anastomotic leak remains an important concern. We report our technique and results combining TaTME with delayed coloanal anastomosis (DCAA) without bowel diversion. First, the splenic flexure, left colon and rectum are laparoscopically mobilized to mid-rectum. TaTME is performed to complete the distal rectal mobilization, and the specimen is delivered transanally and transected. The abdominoperineal colonic pull-through is secured to the anal canal and hypertonic dressing is applied regularly in the ward. The handsewn DCAA is performed one week later. An accompanying video demonstrates this technique. Five consecutive patients with low rectal cancer underwent TaTME with DCAA. All had upfront surgical resection except one who underwent total neoadjuvant therapy. Mean operative duration, blood loss, and length of hospital stay was 290 (250-375) min, 142 (10-200) ml and 11.6 (10-14) days respectively. One patient (20%) suffered a postoperative complication of persistent urinary retention, requiring an indwelling urinary catheter on discharge. There were no cases of open conversion and no instances of anastomotic leakage. Two patients (40%) had minor low anterior resection syndrome (LARS) and one (20%) had major LARS. TaTME and DCAA without stoma are complimentary techniques that augment the minimally invasive effects of laparoscopic sphincter-sparing low rectal cancer surgery, with good perioperative outcomes.

Obstructive sleep apnea in people with intellectual disabilities: adherence to and effect of CPAP.

PURPOSE: Obstructive sleep apnea (OSA) is common in people with intellectual disabilities (ID), but in practice continuous positive airway pressure (CPAP) is often deemed unfeasible. We investigated adherence to and effect of CPAP in patients with ID and OSA. METHODS: Patients with ID were started on CPAP using an intensive training program. Acceptable adherence was defined as use of ≥ 4 h/night during ≥ 70% of the nights. Treatment effect was measured with a patient global impression scale and customized questionnaires. Reasons for not starting CPAP, factors influencing treatment, and reasons for terminating CPAP were explored. RESULTS: Of 39 patients with ID, 87% after 8-10 weeks and 70% at 8 months still used CPAP, of whom 74% and 77% showed acceptable adherence. Baseline apnea-hypopnea (AHI) index decreased from 41.2/h to 5.3/h after 8-10 weeks (p < 0.001), and 4.3/h after 8 months (p < 0.001). At 8-10 weeks and after 8 months, there was an improvement in the most restrictive reported complaint (both p < 0.0005), difficulty waking up (p < 0.01; p < 0.0005), handling behavior (p < 0.03; p < 0.02), presence of irritability (p < 0.01), and sleepiness (p < 0.05). The expectation that CPAP would not be tolerated was the main reason for not starting. CPAP use in the first 2 weeks predicted adherence at 8-10 weeks and 8 months (r = 0.51, p < 0.01; r = 0.69, p < 0.01). Of 13 patients who terminated CPAP, the reasons for termination included behavioral problems, comorbid insomnia, anxiety, discomfort, or other side effects. CONCLUSIONS: With adequate guidance, CPAP is both feasible and effective in people with ID and OSA.

Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.

The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location because SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres, with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high-level SHH signaling compared with GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene-expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide insights into intrinsic differences within GCPs that impact on SHH-MB progression.

Bone mineral density and fractures in institutionalised children with epilepsy and intellectual disability.

BACKGROUND: Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). METHODS: A dual-energy X-ray absorptiometry of lumbar spine (L1-L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. RESULTS: Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > - 2.0). Of the 16 children with a low BMD (Z-score ≤ - 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28-2.50 mmol/L) and (supplemented) vitamin D (16-137 nmol/L) were within the normal range. CONCLUSIONS: This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.

MEMRI-based imaging pipeline for guiding preclinical studies in mouse models of sporadic medulloblastoma.

PURPOSE: Genetically engineered mouse models of sporadic cancers are critical for studying tumor biology and for preclinical testing of therapeutics. We present an MRI-based pipeline designed to produce high resolution, quantitative information about tumor progression and response to novel therapies in mouse models of medulloblastoma (MB). METHODS: Sporadic MB was modeled in mice by inducing expression of an activated form of the Smoothened gene (aSmo) in a small number of cerebellar granule cell precursors. aSmo mice were imaged and analyzed at defined time-points using a 3D manganese-enhanced MRI-based pipeline optimized for high-throughput. RESULTS: A semi-automated segmentation protocol was established that estimates tumor volume in a time-frame compatible with a high-throughput pipeline. Both an empirical, volume-based classifier and a linear discriminant analysis-based classifier were tested to distinguish progressing from nonprogressing lesions at early stages of tumorigenesis. Tumor centroids measured at early stages revealed that there is a very specific location of the probable origin of the aSmo MB tumors. The efficacy of the manganese-enhanced MRI pipeline was demonstrated with a small-scale experimental drug trial designed to reduce the number of tumor associated macrophages and microglia. CONCLUSION: Our results revealed a high level of heterogeneity between tumors within and between aSmo MB models, indicating that meaningful studies of sporadic tumor progression and response to therapy could not be conducted without an imaging-based pipeline approach.

Classification of intellectual disability according to domains of adaptive functioning and between-domains discrepancy in adults with epilepsy.

BACKGROUND: In the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5), the diagnostic criteria of intellectual disability (ID) include three domains of adaptive deficits: the conceptual, social and practical. Substantial intra-individual differences between domains can be considered an ID domain discrepancy. METHOD: We explored the associations between ID domains, discrepancies and epilepsy in 189 adults (mean age = 47.9; SD = 15.6). Each DSM-5 ID domain was assessed separately, using subscales of the Vineland II for the social and practical domains, and psychological instruments, including intelligence tests, for the conceptual domain. A set of standardised criteria is proposed to identify an ID domain discrepancy. RESULTS: An ID domain discrepancy seemed to be present in about one-third of subjects and was particularly present in subjects with moderate ID (53.4%). Impairment in the social domain was most often the reason for the discrepancy. The presence of a discrepancy was significantly related to a focal (localised) epilepsy type (OR = 2.3, P = .028) and a mixed seizure type (OR = 1.4, P = .009). Epilepsy characteristics that are indicative of a more severe and refractory epilepsy, including various seizure types, a high seizure frequency, a combined epilepsy type (both focal and generalised epilepsy) and an early age at onset, were significantly related to more severe impairments in conceptual, social and practical adaptive behaviour (all P values <.01). CONCLUSIONS: With a substantial proportion of the subjects who had both ID and epilepsy with an ID discrepancy, professionals should be aware of this and take all domains of ID into account when studying or working with this vulnerable population.

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.

Background: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.

Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

[The role of photodynamic therapy for the treatment of stage I and II carcinoma of the lip]. / De rol van fotodynamische therapie bij de behandeling van het stadium I en II lipcarcinoom.

In this research project the outcomes of photodynamic therapy for the treatment of stage I and II carcinoma of the lip are presented. Retrospectively, 15 patients diagnosed with a primary stage I or II lip carcinoma and treated with meta-tetra hydroxyphenyl chlorin mediated photodynamic therapy were evaluated. The primary outcome measure was disease free survival; the secondary outcome measure was the functional and aesthetic outcome after treatment. A total of 16 primary lip carcinomas were evaluated (75% stage I; 25% stage II). In 94% of the primary lip carcinomas, photodynamic therapy led to a complete remission after a variable follow-up of 14 months to 11 years. The functional and aesthetic long-term outcomes were considered excellent. Photodynamic therapy for the treatment of stage I and II lip carcinoma has a disease free survival rate comparable to surgery or radiotherapy and has outstanding functional and aesthetic outcomes.

The role of Indonesian patients' health behaviors in delaying the diagnosis of nasopharyngeal carcinoma.

BACKGROUND: With an estimated 13,000 newly diagnosed patients per year, nasopharyngeal carcinoma (NPC) is one of the most common types of cancer in males in Indonesia. Moreover, most patients are diagnosed at an advanced stage of the disease. This study aimed to explore the health behaviors of patients diagnosed with NPC and the possible causes of patient delay in NPC diagnosis. METHODS: A qualitative research method was used to gain better insight into patient behaviors. Twelve patients were interviewed using semi-structured interview guidelines. All interviews were recorded, transcribed verbatim and analyzed according to a standard content analysis framework. RESULTS: Most patients had limited knowledge regarding NPC and its causes. Fifty percent of the patients had a delay of six months from the onset of symptoms to diagnosis. The main reason for this delay was the lack of awareness among the patients, which was influenced by their environment, economic status, family, culture, and religion. The perceived barriers to seeking medical help included direct non-medical costs not covered by health insurance, complex and time-consuming insurance and referral systems, and negative experiences in the past. Health insurance did motivate people to seek medical help. CONCLUSION: This study provides additional insight into patients' motivations to delay seeking medical help and can facilitate the design of NPC education programs. To improve awareness of the abovementioned causes for delay, community-based education programs are highly warranted and should focus on the recognition of NPC symptoms and possible solutions to overcome the main barriers at an earlier disease stage.

Palliative surgical intervention in metastatic colorectal carcinoma: a prospective analysis of quality of life.

AIM: Quality of life (QOL) was assessed after palliative surgery for incurable metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with incurable metastatic CRC who were offered elective palliative surgical intervention were included. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL at baseline and at 3 and 6 months after surgery. Generalized estimating equations were used to estimate the mean change in the QOL score from baseline. RESULTS: Twenty-four patients formed the study group. Sixteen underwent resection of the primary tumour and eight had a proximal diversion or bypass. The Global Health (GH) score and Social Functioning (SF) score improved at 3 and 6 months after intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months) and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012). Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable metastatic CRC, surgery improved QOL.

Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group.

This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51-3.5) and 2.3 (95 % CI 1.72-5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment.

Intralesional Injection of OK-432 in Cystic Hygroma.

BACKGROUND: Lymphangiomas are congenital malformations of the lymphatic system with characteristic dilated endothelium-lined spaces. It is vulnerability to infection or chemical irritants cause spontaneous reduction in size and in some cases complete resolution. Intralesional injection of OK-432 or Picibanil (lyophilized incubation mixture of Group A Streptococcus pyogenes of human origin) is slowly gaining recognition as its safety and efficacy standards have shown to avoid complications resulting from surgical interventions. The objective of this study was to evaluate the clinical outcomes of cystic hygroma patients who received OK-432 injections. METHODS: In between 2011 and 2013, six patients with cystic hygroma received intralesional injection of OK-432. All the patients were assessed clinically and radiologically either via ultrasound, computer tomography (CT) or magnetic resonant imaging (MRI) prior to and after receiving the injections. Patients' response towards treatment was classified as total shrinkage, marked shrinkage (greater than 50% reduction in size), slight shrinkage (less than 50% reduction in size) or non-responsive to treatment. RESULTS: Mean duration of follow-up was 12 months. Total shrinkage was achieved in one patient, marked shrinkage in three patients and one patient experienced mild shrinkage. Only one out of the six patients showed no response to treatment. None of the patients in this study experienced serious complications or adverse effects post intralesional injection of OK-432. CONCLUSIONS: Intralesional OK-432 injection is an effective and safe alternative in treating cystic hygroma.

Autism and behavior in adult patients with Dravet syndrome (DS).

INTRODUCTION: Autism and behavioral characteristics in adults with Dravet syndrome (DS) have rarely been systematically studied. METHOD: Three scales were used to assess the outcomes of DS in adulthood in terms of autism and behavior. All the adult patients with DS, nine male and four female, aged between 18 and 60 years, living at the Epilepsy Center Kempenhaeghe in The Netherlands were included in the study. In addition, the past medical history of each patient was systematically screened for diagnoses like autism, Pervasive Development Disorder-Not Otherwise Specified (PDD-NOS), autism spectrum disorder (ASD), hyperactivity, Attention Deficit Hyperactivity Disorder (ADHD), and self-mutilation. Information concerning past and current use of psychoactive drugs was also evaluated. RESULTS: Eight patients (61.5%) were classified as having autism spectrum disorder (ASD) according to the AVZ-R or according to the medical record. Self-mutilation was seen in four patients (30.8%), hyperactivity in none. Three patients (23.1%) currently used psychoactive drugs. CONCLUSION: Autism spectrum disorders persist in adult patients with DS, while certain characteristics associated with behavioral problems, such as hyperactivity or use of psychoactive medication, seem to be less prominent than in childhood.

Investigational lymphatic imaging at the bedside in a pediatric postoperative chylothorax patient.

Chylothorax is a rare but serious complication in children who undergo heart surgery. Its pathogenesis is poorly understood, and invasive surgical treatments are considered only after conservative management fails. Current diagnostic imaging techniques, which could aid decision making for earlier surgical intervention, are difficult to apply. Herein, we deployed near-infrared fluorescence (NIRF) lymphatic imaging to allow the visualization of abnormal lymphatic drainage in an infant with postoperative chylothorax to guide the choice of surgical management. A 5-week-old male infant, who developed chylothoraces after undergoing Norwood surgery for hypoplastic left heart syndrome, was intradermally administered trace doses of indocyanine green in both feet and the left hand. NIRF imaging was then performed at the bedside to visualize lymphatic drainage patterns. Imaging results indicated impeded lymphatic drainage from the feet toward the trunk with no fluorescence in the chest indicating no leakage of peripheral lymph at the thoracic duct. Instead, lymph drainage occurred from the axilla directly into the pleural cavity. As a result of imaging, left pleurodesis was performed to stop the pleural effusion with the result of temporary decrease of left chest tube drainage. Although additional studies are required to understand normal and abnormal lymphatic drainage patterns in infants, we showed the potential of using NIRF lymphatic imaging at the bedside to visualize the lymphatic drainage pathway to guide therapy. Timely management of chylothorax may be improved by using NIRF imaging to understand lymphatic drainage pathways.

KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.

mTHPC-mediated photodynamic therapy of early stage oral squamous cell carcinoma: a comparison to surgical treatment.

BACKGROUND: mTHPC-mediated photodynamic therapy (PDT) is used for treatment of early head and neck squamous cell carcinoma. This study is a retrospective comparison of PDT with transoral surgery in the treatment of early primary squamous cell carcinoma of the oral cavity/oropharynx. METHODS: PDT data were retrieved from four study databases; surgical results were retrieved from our institutional database. To select similar primary tumors, infiltration depth was restricted to 5 mm for the surgery group. A total of 126 T1 and 30 T2 tumors were included in the PDT group, and 58 T1 and 33 T2 tumors were included in the surgically treated group. RESULTS: Complete response rates with PDT and surgery were 86 and 76% for T1, respectively, and for T2 63 and 78%. Lower local disease-free survival for PDT compared to surgery was found. However, when comparing the need for local retreatment, no significant difference for T1 tumors was found, while for T2 tumors surgery resulted in significantly less need for local retreatment. No significant differences in overall survival between surgery and PDT were observed. CONCLUSIONS: PDT for T1 tumors results in a similar need for retreatment compared to surgery, while for T2 tumors PDT performs worse. Local disease-free survival for surgery is better than for PDT. This may be influenced by the benefit surgery has of having histology available. This allows an early decision on reintervention, while for PDT one has to follow a wait-and-see policy. Future prospective studies should compare efficacy as well as morbidity.