Deciphering Genetic Alterations of Taiwanese Patients with Pancreatic Adenocarcinoma through Targeted Sequencing.

Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related deaths in Taiwan, and its incidence is increasing. The development of PAC involves successive accumulation of multiple genetic alterations. Understanding the molecular pathogenesis and heterogeneity of PAC may facilitate personalized treatment for PAC and identify therapeutic agents. We performed tumor-only next-generation sequencing (NGS) with targeted panels to explore the molecular changes underlying PAC patients in Taiwan. The Ion Torrent Oncomine Comprehensive Panel (OCP) was used for PAC metastatic lesions, and more PAC samples were sequenced with the Ion AmpliSeq Cancer Hot Spot (CHP) v2 panel. Five formalin-fixed paraffin-embedded (FFPE) metastatic PAC specimens were successfully assayed with OCP, and KRAS was the most prevalent alteration, which might contraindicate the use of anti-EGFR therapy. One PAC patient harbored a FGFR2 p. C382R mutation, which might benefit from FGFR tyrosine kinase inhibitors. An additional 38 samples assayed with CHP v2 showed 100 hotspot variants, collapsing to 54 COSMID IDs. The most frequently mutated genes were TP53, KRAS, and PDGFRA (29, 23, 10 hotspot variants), impacting 11, 23, and 10 PAC patients. Highly pathogenic variants, including COSM22413 (PDGFRA, FATHMM predicted score: 0.88), COSM520, COSM521, and COSM518 (KRAS, FATHMM predicted score: 0.98), were reported. By using NGS with targeted panels, somatic mutations with therapeutic potential were identified. The combination of clinical and genetic information is useful for decision making and precise selection of targeted medicine.

Long-term Follow-up of Patients With Hernia Using the Hernia-Specific Quality-of-Life Mobile App: Feasibility Questionnaire Study.

BACKGROUND: Hernia repair is one of the most common surgical procedures; however, the long-term outcomes are seldom reported due to incomplete follow-up. OBJECTIVE: The aim of this study was to examine the use of a mobile app for the long-term follow-up of hernia recurrence, complication, and quality-of-life perception. METHODS: A cloud-based corroborative system drove a mobile app with the HERQL (Hernia-Specific Quality-of-Life) questionnaire built in. Patients who underwent hernia repair were identified from medical records, and an invitation to participate in this study was sent through the post. RESULTS: The response rate was 11.89% (311/2615) during the 1-year study period, whereas the recurrence rate was 1.0% (3/311). Causal relationships between symptomatic and functional domains of the HERQL questionnaire were indicated by satisfactory model fit indices and significant regression coefficients derived from structural equational modeling. Regarding patients' last hernia surgeries, 88.7% (276/311) of the patients reported them to be satisfactory or very satisfactory, 68.5% (213/311) of patients reported no discomfort, and 61.1% (190/311) of patients never experienced mesh foreign body sensation. Subgroup analysis for the most commonly used mesh repairs found that mesh plug repair inevitably resulted in worse symptoms and quality-of-life perception from the group with groin hernias. CONCLUSIONS: The mobile app has the potential to enhance the quality of care for patients with hernia and facilitate outcomes research with more complete follow-up.

An examination of surgical and survival outcomes in the elderly (65-79 years of age) and the very elderly (≥80 years of age) who received surgery for gastric cancer.

Objective: The purpose of this study was to examine surgical and survival outcomes in the elderly (65-79 years of age) and the very elderly (≥80 years of age) who received surgery for gastric cancer.Methods: This study retrospectively reviewed the records of patients ≥65 years old who received a gastrectomy for gastric adenocarcinoma. Demographic, clinical, and pathological data were extracted from the medical records. Patients were divided into two groups: those 65-79 years of age and those ≥80 years of age. Data and survival outcomes were compared between the groups.Results: Sixty-four patients were included, 32 males and 32 females. The mean age in the 65-79 years old group was 73.4 ± 4.5 years, and in the ≥80 years group was 85.2 ± 3.4 years (p < .001). Three patients in the older group had chronic kidney disease, as compared to none in the 65-79 years group (p = .04); all other demographic, clinical, tumor, and surgical characteristics were similar between the groups, except for surgical time (all, p > .05). Patients ≥80 years had a higher incidence of pulmonary complications (24% vs 4.7%, p = .03), but there was no significant difference in in-hospital mortality. The ≥80 years group had a higher overall survival, but the difference between the groups was not statistically significant (42.9% and 34.9%, p = .224).Conclusions: Curative intent resection, gastrectomy with D1+/D2 lymph node dissection is a viable option for elders ≥80 years old with gastric carcinoma.

Warfarin Overdose Associated Inferior Mesentery Artery Aneurysm Rupture Mimicking Spontaneous Bowel Hematoma.

Inferior mesentery artery (IMA) aneurysm rupture is easily overlooked in patients with abdominal pain due to its uncommon occurrence. It may result in catastrophic consequence once misdiagnosed as spontaneous bowel hematoma in patients with anticoagulant overdose and intra-abdominal hematoma, as treatment strategy for both diseases varies differently. We present a case of a 70-year-old male who came to our emergency department with the chief complaint of abdominal pain over periumbilical area, eventually diagnosed as anticoagulant overdose associated IMA aneurysm rupture without occlusion of superior mesentery artery (SMA) and celiac artery (CA). This case report alerts us to consider the rare other source of bleeding, for instance ruptured inferior mesentery aneurysm, while encountering such an extraordinary large intra-abdominal hematoma in patients on anticoagulant.

System approach to prevent common bile duct injury and enhance performance of laparoscopic cholecystectomy.

Experience collected from 5200 cases of laparoscopic cholecystectomy (LC) and 29 patients (6 ours, 23 referred) with major common bile duct (CBD) injury during LC in our institute between December 1990 and July 2004 was reported to demonstrate that the system approach we applied in performing LC prevents CBD injury and enhances surgical performance. Each case of CBD injury was meticulously analyzed to identify causative factors. We developed preventive strategies focusing on 4 dimensions: patient, environment, procedure, and operator. Surgical performance was then evaluated to demonstrate improvements. Incidence of CBD injury was calculated for early and latter halves of the series to compare 5 parameters of surgical performance: patient selection, operation time, indwelling drainage tube, surgeon, and conversion rate. Results of accident analysis demonstrated that CBD injury followed definite mechanisms; several warning signs appearing before and during injury were identified and classified. According to these results, we designed strategies to prevent injury, including: setting up patient-selection program, controlling surgical environment, developing error-proof procedures, and constructing training programs. Incidence of CBD injury in the whole series was 0.12% (6/5200), 0.27% in early half (6/2224), and zero (0/2967) in latter half. Attending doctors had significantly shorter operation times in latter period for both elective and emergent LC. Rate of using drainage tubes for elective surgery by attending doctors was significantly decreased in latter period. Operation time for elective surgery by residents was similar in both early and latter periods. However, residents in latter period had longer operation times (around 23 min long, P<0.001) for emergent LC. Steps of our system approach include: (1) detailed accident analysis focusing on patient, environment, procedure, and surgeon; (2) developing 4 strategies directly responding to accident analysis results, including proper patient selection, control of environment, error-proof procedures, and a well-designed training program; and (3) demonstrating improved patient safety and surgical performance. Consistent use of systems approach promises continuing quality improvement. We believe our working model will help perform safer LC and also benefit other medical disciplines.

Quality of life of inguinal hernia patients in Taiwan: The application of the hernia-specific quality of life assessment instrument.

BACKGROUND: With the development of prosthetic mesh and tension free techniques, the recurrence rate following inguinal hernia repair has been reduced, and hernia outcomes research should focus on post-operative quality of life and potential complications. STUDY DESIGN: A novel hernia quality of life assessment instrument, HERQL, was developed. The HERQL questionnaire comprises a 4-item summative pain score measuring pain and discomfort resulting from various strenuous activities. Symptomatic and functional domains, as well as post-operative satisfaction are evaluated as well. RESULTS: A total of 386 HERQL surveys were completed by 183 patients with inguinal hernias. Internal consistency reliability of the summative pain score was satisfactory, with a Cronbach's alpha of 0.85. Criterion validity was examined by concomitant assessment of the pain/discomfort and health impact subscales of the EQ-5D questionnaire, with substantial to moderate correlations. Pre-operative patients reported more severe hernia protrusion, more pain during mild to heavy exercise, and worse activity restriction and health impairment than the follow-up patients, indicating clinical validity. The conceptual structure of the HERQL demostrated the causal relationship between the formative symptomatic subscales and the reflective functional status indicators. Repeated measurement of the summative pain scores revealed an estimated time effect of -1.63, which was the rate of change in the summative pain score across the pre-operative, immediately post-operative, and follow-up 3-month periods suggesting the clinical responsiveness of the HERQL. CONCLUSIONS: This study will facilitate inguinal hernia outcomes research and enhance the quality of care for this common disease by providing a validated HERQL instrument with enhanced sensitivity.

Laparoscopic common bile duct exploration with T-tube choledochotomy for the management of choledocholithiasis.

Although laparoscopic cholecystectomy (LC) has become the gold standard for the management of gallstone disease, the application of laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis has been slower. The aim of this study is to determine the feasibility and effectiveness of LCBDE. A retrospective cohort study was conducted to compare LCBDE (n = 82) with conventional common bile duct exploration (CCBDE) (n = 75) and endoscopic sphincterotomy (EST) (n = 80) in the management of choledocholithiasis. All our LCBDEs were performed through choledochotomy with T-tube placement. The mean operative time of the LCBDE group (124 +/- 48 minutes) was not significantly longer then the CCBDE group (118 +/- 35 minutes), while the postoperative hospitalization was shorter in both the LCBDE (8 +/- 5 days) and EST (9 +/- 4 days) groups than in the CCBDE (13 +/- 6 days) group. In the LCBDE group, 14 patients (17.1%) required postoperative choledochoscopy to clear residual stones through the T-tube tract. The only mortality occurred in the CCBDE group. The morbidity rate was 3.7% (3/82) in the LCBDE group, including bile leakage in 1 case and bile peritonitis in 2 cases; 6.7% (5/75) in the CCBDE group, including atlectasis in 2 cases, sepsis in 1, and wound infection in 2. There were 2 cases of postoperative pancreatitis (2.5%; 2/80) in the EST group. The difference in the average number of sessions needed for complete clearance of choledocholithiasis in each group was statistically significant (EST, 1.46 +/- 0.67; LCBDE, 1.23 +/- 0.42; and CCBDE, 1.09 +/- 0.28; P < 0.0001). Our results suggested that EST and LCBDE tended to require more therapeutic sessions then CCBDE, although these sessions were less invasive. The benefits of LCBDE include minimal invasiveness, concurrent treatment of gallbladder stone and CBD stones in a single session, and a shorter postoperative hospital stay. However a longer learning curve is needed. Selection of the most suitable therapeutic option for individual patients by an experienced surgeon gives the most benefits to patients.

Surgical site infection and timing of prophylactic antibiotics for appendectomy.

BACKGROUND: Pre-operative prophylactic antibiotics may decrease the frequency of surgical site infection after appendectomy. However, the optimal timing for administration of pre-operative prophylactic antibiotics is unknown. The purpose of this study was to evaluate the effect of timing of prophylactic antibiotics on the frequency of surgical site infection after appendectomy. METHODS: Medical records were reviewed retrospectively for 577 consecutive patients who had appendectomy for acute appendicitis from 2006 to 2009. Quality assurance guidelines for timing of prophylactic antibiotics before the skin incision were changed from 0 to 30 min before the skin incision (before June 2008) to 30 to 60 min before the skin incision (after June 2008). RESULTS: Surgical site infection occurred in 28 patients (4.9%). There was no difference in frequency of surgical site infection with different timing of pre-operative prophylactic antibiotic (pre-operative time 0 to 30 min: 9 infections [3.6%]; 31 to 60 min: 13 infections [5.4%]; 61 to 120 min: 5 infections [7.0%]; >120 min: 1 infection [6.6%]). Multivariable analysis showed that surgical site infection was associated significantly with medical comorbidity but not perforated appendicitis. CONCLUSIONS: The frequency of surgical site infection was independent of timing of preoperative prophylactic antibiotics but was associated with the presence of medical comorbidity.

Management of bile leakage after laparoscopic cholecystectomy based on etiological classification.

PURPOSE: To analyze and classify bile leakage after laparoscopic cholecystectomy (LC) according to its etiology. This classification will help to determine the most appropriate management strategy, whereby unnecessary intervention can be avoided. METHODS: We examined the medical records of 16 patients in whom bile leakage occurred as a complication of LC. RESULTS: Bile leakage was classified according to its cause into the following groups: insecure closure of the cystic duct stump (n = 3); retention of a common bile duct (CBD) stone (n = 1); CBD injury (n = 10); unsuspected accessory bile ducts (n = 1); and unknown origin (n = 1). The management strategies included observation (n = 3), laparoscopic intervention with drainage (n = 4), laparotomy with drainage (n = 3), and laparotomy with Roux-en-Y choledochojejunostomy for CBD transection (n = 6). All 16 patients recovered uneventfully with similar hospitalization. CONCLUSIONS: Bile leakage is not always caused by bile duct injury, and it would be inappropriate to attribute leakage to bile duct injury if there is a retained CBD stone, an unsuspected accessory duct, or an unsecured cystic duct stump. Thus, the management of each condition should vary accordingly. Reviewing a videotape of the surgery and early cholangiogram can help to establish the etiological diagnosis and select the most appropriate course of action.