Impacts of different pancreatic resection ranges on endocrine function in Suncus murinus

BACKGROUND Surgical intervention involving the pancreas can lead to impaired glucose tolerance and other types of endocrine dysfunction.The scope of pancreatectomy and whether it includes the ventral pancreas are the key factors in the development of postoperative diabetes.The ventral and dorsal pancreases are almost separated in Suncus murinus(S.murinus).AIM To investigate the effects of different extents of pancreatic resection on endocrine function in S.murinus.METHODS Eight-week-old male S.murinus shrews were randomly divided into three experimental groups according to different pancreatic resection ranges as follows:ventral pancreatectomy(VPx)group;partial pancreatectomy(PPx)group;subtotal pancreatectomy(SPx)group;and a sham-operated group.Postprandial serum insulin,glucagon-like peptide-1(GLP-1),pancreatic polypeptide(PP),and somatostatin(SST)levels,as well as food intake,weight,blood glucose,and glucose tolerance were regularly measured for each animal.RESULTS S.murinus treated with PPx and SPx suffered from varying degrees of impaired glucose tolerance,but only a small proportion of the SPx group developed diabetes.Only S.murinus in the SPx group showed a significant decrease in food intake accompanied by severe weight loss,as well as a significant increase in postprandial serum GLP-1 levels.Postprandial serum PP levels decreased in both the VPx and PPx groups,but not in the SPx group.Postprandial serum SST levels decreased in both VPx and PPx groups,but the decrease was marginal.CONCLUSION Severe weight loss after pancreatectomy may be related to loss of appetite caused by compensatory elevation of GLP-1.PP and GLP-1 may play a role in resisting blood glucose imbalance.

TTYH2,a human homologue of the Drosophila melanogaster gene tweety,is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation

AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 signifi cantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the fi rst time, that the TTYH2 gene expression is signifi cantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating andmetastatic potentials of colorectal cancer.

Identification of anticancer drugs to radiosensitise BRAF-wild-type and mutant colorectal cancer

Objective: Patients with BRAF-mutant colorectal cancer(CRC) have a poor prognosis. Molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF status.Methods: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in vivo.Results: Most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1(BRAF-wildtype) cells and 1.8 in RKO(BRAF V600 E) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth(P ≤ 0.01).Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds.

Complementary and alternative medicine use by Japanese children with pediatric surgical diseases

Background: This study aimed to survey the use of complementary and alternative medicine (CAM) therapies in Japanese children with major pediatric surgical diseases. Methods: This survey was mailed to each family of 355 patients. Results: One hundred fifty-three (43%) of 355 mailed questionnaires were completely returned. Forty-one (27%) of 153 parents responded that they used CAM for their child. There was no significant difference in CAM use according to sex, mean age, follow-up duration, family CAM users, and associated disorders between CAM users and non-users. Children with inflammatory bowel disease (IBD) were significantly more likely to use CAM than children without IBD (65% vs 21%, p = 0.0001). Only 20% of parents informed the attending physicians about CAM before its use. Conclusions: It is important for physicians caring for children with pediatric surgical disease, especially IBD, to be familiar with common forms of CAM.

Diffusion-weighted imaging might be useful for reactive lymphoid hyperplasia diagnosis of the liver: A case report

BACKGROUND Reactive lymphoid hyperplasia(RLH)of the liver is a rare liver lesion.It is considered difficult to differentiate radiologically from hepatocellular carcinoma,metastatic liver tumor and other pathologies.CASE SUMMARY A 54-year-old woman presented to our hospital with RLH of the liver.The patient had a diagnosis of metastatic carcinoma of the liver from an unknown origin and subsequently underwent partial hepatectomy.However,histopathological analysis revealed RLH.The lesion showed perinodular enhancement in the arterial phase on contrast-enhanced computed tomography and magnetic resonance imaging.On diffusion-weighted imaging(DWI),we encountered linear hyperintensity along the portal tract consecutive to the liver lesion,which is a new characteristic radiologic finding.This finding corresponded to the lymphoid cell infiltration of the portal tract.Furthermore,there was strongly restricted diffusion on the apparent diffusion coefficient map.We used these characteristic radiologic findings to diagnose the lesion as a lymphoproliferative disease.CONCLUSION The linear hyperintensity consecutive to the liver lesion on DWI provided additional valuable diagnostic information.

Comparison of effects of six main gastrectomy procedures on patients’ quality of life assessed by Postgastrectomy Syndrome Assessment Scale-45

BACKGROUND The effects of various gastrectomy procedures on the patient’s quality of life(QOL)are not well understood.Thus,this nationwide multi-institutional crosssectional study using the Postgastrectomy Syndrome Assessment Scale-45(PGSAS-45),a well-established questionnaire designed to clarify the severity and characteristics of the postgastrectomy syndrome,was conducted.AIM To compare the effects of six main gastrectomy procedures on the postoperative QOL.METHODS Eligible questionnaires retrieved from 2368 patients who underwent either of six gastrectomy procedures[total gastrectomy with Roux-en-Y reconstruction(TGRY;n=393),proximal gastrectomy(PG;n=193),distal gastrectomy with Roux-en-Y reconstruction(DGRY;n=475),distal gastrectomy with Billroth-I reconstruction(DGBI;n=909),pylorus-preserving gastrectomy(PPG;n=313),and local resection of the stomach(LR;n=85)]were analyzed.Among the 19 main outcome measures of PGSAS-45,the severity and characteristics of postgastrectomy syndrome were compared for the aforementioned six gastrectomy procedures using analysis of means.RESULTS TGRY and PG significantly impaired the QOL of postoperative patients.Postoperative QOL was excellent in LR(cardia and pylorus were preserved with minimal resection).In procedures removing the distal stomach,diarrhea subscale(SS)and dumping SS were less frequent in PPG than in DGBI and DGRY.However,there was no difference in the postoperative QOL between DGBI and DGRY.The most noticeable adverse effects caused by gastrectomy were mealrelated distress SS,dissatisfaction at the meal,and weight loss,with significant differences among the surgical procedures.CONCLUSION Postoperative QOL greatly differed among six gastrectomy procedures.The severity and characteristics of postgastrectomy syndrome should be considered to select gastrectomy procedures,overcome surgical shortcomings,and enhance postoperative care.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy

Objective: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival.Methods: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation.Results: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age(year), symptom(no/yes), tumor size at initial diagnostic stage(cm), preoperative serum carbohydrate antigen(CA) 19-9 level after neoadjuvant treatment(<34/≥34 U/m L), and planned surgery [pancreaticoduodenectomy(PD)(pylorus-preserving PD)/distal pancreatectomy(DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration.The calibration plot showed good agreement between actual and predicted survival probabilities;the the Greenwood-Nam-D’Agostino(GND) goodness-of-fit test showed that the model was well calibrated(χ~2=8.24,P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups(P=0.044).Conclusions: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Safety and feasibility of laparoscopic pancreatoduodenectomy

Laparoscopic pancreaticoduodenectomy(LPD)has been safely performed by experts with favorable surgical outcomes.However,the feasibility of LPD remains controversial.LPD is generally considered a challenging operation that requires advanced laparoscopic techniques.In particular,pancreatic reconstruction can be safely performed by only laparoscopic experts.Thus,guidelines created by LPD experts are valuable in indicating the future direction of LPD.Qin et al.developed practical guidelines regarding the safety and feasibility of LPD with 28 international experts from eight countries(1).To create these guidelines,the first summit on minimally invasive pancreatico-biliary surgery was held in Wuhan,China,to promote the development of LPD.Based on a systematic literature review and expert opinions,16 statements were created by the experts.These statements provide useful guidelines not only for surgical trainees who will attempt LPD but also for specialized surgeons.This expert consensus will contribute to the safe implementation of LPDs in the future.

International consensus statement on robotic pancreatic surgery

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of;evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

Difficult procedures,better outcomes

Despite the initial skepticism and challenges,minimally invasive liver surgery especially laparoscopic liver resections(LLR),has become a first-choice surgical treatment for various liver tumors in many specialized centers worldwide(1-3).It is a safe alternative to open surgery thanks to advantages such as reduced blood loss and complication rates,shorter hospital stay,and better quality of life(4-7).However,laparoscopy requires relatively long learning,and complex procedures are limited to high-volume expert centers(8).