Publications by authors named "Jin-Tung Liang"

110 Publications

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Br J Cancer 2021 Apr 12. Epub 2021 Apr 12.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.

Methods: We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC.

Results: Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m was significantly associated with CIMP-high CRC in younger patients.

Conclusions: We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m and CIMP-high CRC in patients younger than 50 years.
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http://dx.doi.org/10.1038/s41416-021-01300-5DOI Listing
April 2021

Applicability of minimally invasive surgery for clinically T4 colorectal cancer.

Sci Rep 2020 11 23;10(1):20347. Epub 2020 Nov 23.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, ROC.

The role of minimally invasive surgery (MIS) to treat clinically T4 (cT4) colorectal cancer (CRC) remains uncertain and deserves further investigation. A retrospective cohort study was conducted between September 2006 and March 2019 recruiting patients diagnosed as cT4 CRC and undergoing MIS at a university hospital and its branch. Patients' demography, clinicopathology, surgical and oncological outcomes, and radicality were analyzed. A total of 128 patients were recruited with an average follow-up period of 33.8 months. The median time to soft diet was 6 days, and the median postoperative hospitalization periods was 11 days. The conversion and complication (Clavien-Dindo classification ≥ II) rates were 7.8% and 27.3%, respectively. The 30-day mortality was 0.78%. R0 resection rate was 92.2% for cT4M0 and 88.6% for pT4M0 patients. For cT4 CRC patients, the disease-free survival and 3-year overall survival were 86.1% and 86.8% for stage II, 54.1% and 57.9% for stage III, and 10.8% and 17.8% for stage IV. With acceptable conversion, complication and mortality rate, MIS may achieve satisfactory R0 resection rate and thus lead to good oncological outcomes for selected patients with cT4 CRC.
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http://dx.doi.org/10.1038/s41598-020-77317-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683557PMC
November 2020

Study protocol for an International Prospective Observational Cohort Study for Optimal Bowel Resection Extent and Central Radicality for Colon Cancer (T-REX study).

Jpn J Clin Oncol 2021 Jan;51(1):145-155

Tokyo Medical and Dental University, Tokyo, Japan.

This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of 'regional' lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481).
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http://dx.doi.org/10.1093/jjco/hyaa115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767979PMC
January 2021

Metronomic chemotherapy with tegafur-uracil following radical resection in stage II colorectal cancer.

J Formos Med Assoc 2021 May 3;120(5):1194-1201. Epub 2020 Oct 3.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Background: Stage II colorectal cancer has a relatively good prognosis. Adjuvant chemotherapy following surgery is the standard treatment for stage III colorectal cancer but is not routinely recommended for all stage II colorectal cancer patients. We aimed to evaluate the clinical outcomes, treatment results, and prognostic factors in stage II colorectal cancer patients who underwent curative surgery with/without oral tegafur-uracil (UFT).

Methods: We included stage II colorectal cancer patients who underwent curative surgery and were followed up for at least 5 years after surgery at the National Taiwan University Hospital between January 2008 and December 2012. Excluding patients receiving neoadjuvant therapy, adjuvant therapy other than UFT, and those lost follow-up, patients treated with UFT (UFT group) and those without adjuvant therapy (surgery alone group) were analyzed for their clinical outcomes and prognostic factors.

Results: A total of 233 patients were recruited. Of these, 104 (44.64%) underwent only surgery while 129 (55.36%) received adjuvant chemotherapy with oral UFT following surgery. Recurrence or death occurred within 5 years in 60 patients (25.75%), with a significant difference between the surgery alone (36/104, 34.62%) and UFT groups (24/129, 18.61%) (p = 0.007). The UFT group demonstrated significantly superior 5-year disease-free (p = 0.003) and overall survival rates (p = 0.001), respectively. Patient age of ≤35.3 or ˃72.7 years, UFT duration of <486.8 days, 7.1 cm < tumor size ≤13.2 cm, number of harvested lymph nodes ≤13.5, and mucinous adenocarcinoma were associated with poorer 5-year overall survival.

Conclusion: The present data suggest that UFT following curative surgery may be associated with lower recurrence and improved survival in patients with stage II colorectal cancer.
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http://dx.doi.org/10.1016/j.jfma.2020.09.014DOI Listing
May 2021

A Pilot Study of Metabolomic Pathways Associated With Fatigue in Survivors of Colorectal Cancer.

Biol Res Nurs 2021 Jan 22;23(1):42-49. Epub 2020 Jul 22.

School of Nursing, 38005College of Medicine, National Taiwan University, Taipei.

Background: Over 30% of cancer survivors experience chronic fatigue. An alteration in energy metabolism is one of the hypothesized mechanisms for cancer-related fatigue (CRF). No studies have evaluated for changes in metabolic profiles in cancer survivors with CRF. The purpose of this pilot study was to evaluate for differences in metabolic profiles between fatigued and non-fatigued survivors of colorectal cancer (CRC).

Methods: Survivors were recruited from the surgical outpatient department and the oncology clinic of a medical center in northern Taiwan. Fatigue was assessed using the Fatigue Symptom Inventory. Fasting blood samples were collected on the day the fatigue questionnaire was completed. Metabolomic profile analysis was performed using non-targeted, liquid chromatography/time-of-flight mass spectrometry. Fold change analyses, t-tests, and pathway analyses were performed to identify differences in metabolomic profiles between the fatigued and non-fatigued survivors.

Results: Of the 56 CRC survivors in this study, 28.6% (n = 16) were in the fatigue group. Statistically significant differences in carnitine, L-norleucine, pyroglutamic acid, pyrrolidonecarboxylic acid, spermine, hydroxyoctanoic acid, and paraxanthine were found between the two fatigue groups. In addition, two pathways were enriched for these metabolites (i.e., glutathione metabolism, D-glutamine and D-glutamate metabolism).

Conclusions: Findings from this pilot study provide preliminary evidence that two pathways that are involved with the regulation of ATP production and cellular energy (i.e., glutathione metabolism, D-glutamine and D-glutamate metabolism) are associated with fatigue in CRC survivors. If these findings are confirmed, they may provide new therapeutic targets to decrease fatigue in cancer survivors.
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http://dx.doi.org/10.1177/1099800420942586DOI Listing
January 2021

Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer.

Cancers (Basel) 2020 Jun 10;12(6). Epub 2020 Jun 10.

Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.

Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness. We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them. We examined 20 depressed and 13 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 colorectal cancers (CRCs) to clarify the clinical outcome of depressed neoplasms. CNAs in , , and were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with a D-marker panel have significantly shorter progression-free survival compared with those without ( = 0.012), especially in stage I ( = 0.049), stages T ( = 0.027), and proximal cancers ( = 0.002). The positivity of the D-marker panel was an independent risk factor of cancer progression (hazard ratio (95% confidence interval) = 1.52 (1.09-2.11)). Furthermore, the proximal CRCs with D-marker panels had worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those that did not. The D-marker panel may help to optimize treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future.
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http://dx.doi.org/10.3390/cancers12061527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352996PMC
June 2020

Robotic Top-Down Intersphincteric Resection With IPAA for Familial Adenomatous Polyposis With Distal Rectal Cancer.

Dis Colon Rectum 2019 10;62(10):1256-1257

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan.

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http://dx.doi.org/10.1097/DCR.0000000000001303DOI Listing
October 2019

Is single-incision laparoscopic appendectomy suitable for complicated appendicitis? A comparative analysis with standard multiport laparoscopic appendectomy.

Asian J Surg 2020 Jan 23;43(1):282-289. Epub 2019 May 23.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital, College of Medicine, Taiwan, ROC.

Background: Despite emerging evidences on the feasibility and efficacy of single-incision laparoscopic appendectomy (SILA) for managing simple appendicitis, advancing its use for treating complicated appendicitis remains unwarranted. This study aimed to evaluate the surgical outcome of SILA compared with that of standard multiport laparoscopic appendectomy (MPLA) in the management of complicated appendicitis.

Methods: Between July 2013 and September 2017, 40 patients who underwent SILA and 150 patients who underwent MPLA for the treatment of complicated appendicitis, defined as AAST grades II-V, were recruited for this study. The demographic characteristics, intraoperative and recovery parameters were retrospectively recorded. No routine drainage was placed in the SILA group.

Results: SILA was smoothly performed without requiring conversion to MPLA. No significant difference was observed between the 2 groups in demography and preoperative severity. The operation duration was approximately 8 min shorter in the SILA group than in the MPLA group, without a statistical difference (60.03 ± 21.01 vs. 68.04 ± 32.03 min, p = 0.222). The recovery parameters, including soft diet intake and postoperative hospitalization, were more favorable in the SILA group (p < 0.001). Despite the absence of routine drainage in the SILA group, only 1 patient developed an intra-abdominal hematoma necessitating further computed tomography-guided drainage.

Conclusion: SILA is safe and feasible for the management of complicated appendicitis. SILA had non-inferior results to MPLA in terms of time to resume oral intake and postoperative hospital stay. Furthermore, this study posted a question on the concept of routine postoperative drainage in complicated appendicitis.
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http://dx.doi.org/10.1016/j.asjsur.2019.04.014DOI Listing
January 2020

Is robotic hepatectomy cost-effective? In view of patient-reported outcomes.

Asian J Surg 2019 Apr 29;42(4):543-550. Epub 2019 Jan 29.

Department of Surgery, National Taiwan University Hospital, Taiwan. Electronic address:

Background: Robotic hepatectomy has been accepted as an alternative for patients needing surgery. However, few reports addressed the patient-reported outcomes and long-term quality of life (QoL) of patients having undergone robotic liver surgery.

Methods: This study presented the QoL and cost-effectiveness associated with robotic and open hepatectomy by performing a comparative survey using two standardized questionnaires (Short Form-36 and Gastrointestinal Quality of Life Index).

Results: One hundred patients completed the study. The robotic group tended to experienced longer operation time but shorter length of hospital stay compared to open group. Moreover, the robotic group had faster return to daily activities, less need of patient-controlled anesthesia, and less wound-related complaints in long-term follow-up. The robotic group incurred higher peri-operative expenses; however, the cost of inpatient care was lower.

Conclusions: Our study suggested that robotic hepatectomy provided good post-operative QoL and recovery of daily activity. However, efforts for lowering the financial burden of medical care by reducing the cost of robotic surgery is necessary for further application.
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http://dx.doi.org/10.1016/j.asjsur.2018.12.010DOI Listing
April 2019

Toward a fully robotic surgery: Performing robotic major liver resection with no table-side surgeon.

Int J Med Robot 2019 Apr 17;15(2):e1985. Epub 2019 Feb 17.

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.

Background: Evidence has suggested that robotic system helps perform more major liver resections. However, the required table-side surgeon has remained a concern because of the uncertain performance and the incomplete control of console surgeon.

Methods: Data were reviewed for consecutive 333 robotic liver resections, of which 56 patients underwent left liver resection with the usual setting, and 35 with no table-side surgeon.

Results: No conversion was required in the setting with no table-side surgeon. The group without the table-side surgeon had similar complication rates, blood loss, and operative time compared with that of the normal settings, as well as focused analysis on major left hemihepatectomy.

Conclusion: Our data suggest that performing robotic major liver resection without the presence of the table-side surgeon is safe and feasible. The concise performance of robotic platforms might accelerate the machine learning process along with the ability to predict patterns of future autonomous surgery.
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http://dx.doi.org/10.1002/rcs.1985DOI Listing
April 2019

Standardize the Surgical Technique and Clarify the Relevant Anatomic Concept for Complete Mobilization of Colonic Splenic Flexure Using da Vinci Xi Robotic System.

World J Surg 2019 Apr;43(4):1129-1136

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, Taiwan, ROC.

Background: The present study is to set up a standardized approach for complete mobilization of colonic splenic flexure using da Vinci Xi robotic system, based on clarification of the mesenteric structures of distal transverse colon.

Methods: The surgical outcomes and relevant anatomic structures of 104 consecutive patients undergoing robotic resection of primary colorectal cancer with the intent of complete mobilization of colonic splenic flexure using da Vinci Xi robotic system were retrospectively reviewed.

Results: Complete mobilization of colonic splenic flexure can be efficiently performed by the Xi robotic system, as demonstrated by short operation time, minimal intra-operative blood loss, and few surgical complications. Xi robotic system has overcome the drawbacks of Si robotic system for the mobilization of colonic splenic flexure. The present study defined the following anatomic hallmarks for the colonic splenic flexure: (1) The transverse mesocolon distal to the inferior mesenteric vein adheres to the low border of pancreas by the avascular fibrous connective tissues, which have been inappropriately named as "mesenteric root"; (2) The colonic splenic flexure abuts closely to spleen with an acute angle in 78.85% (n = 82/104); (3) Only a minority of patients presented with the Riolan branch (15.38%, n = 16/104) or the Moskowitz artery (8.65%, n = 9/104).

Conclusion: With increased maneuverability of Xi robotic arms and the clarification of relevant anatomic concept, the surgical technique for the complete mobilization of colonic splenic flexure can be standardized; and the standardization of surgical technique is the first step toward the enhanced automation in the rapidly evolving robotic systems.
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http://dx.doi.org/10.1007/s00268-018-04882-zDOI Listing
April 2019

The Toldt fascia: A historic review and surgical implications in complete mesocolic excision for colon cancer.

Asian J Surg 2019 Jan 3;42(1):1-5. Epub 2018 Dec 3.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

To clarify the anatomic concept of Toldt fascia, based on the literature review and the surgical anatomic dissection using laparoscopic or robotic approach. We undertook review of the historic literature and surgical videos from 250 patients with colorectal cancer operated on laparoscopically or robotically to discuss the surgical implications of Toldt fascia in complete mesocolic excision for colon cancer. Toldt fascia, sandwiched by the overlying mesothelial layer of the mesocolon and underlying mesothelial layer of the retroperitoneum, comprised loose fibrous tissues with minute vessels inside, and was contiguous from the ileocecal mesentery radix to the upper rectum. Surgical dissection plane is readily developed within the Toldt fascia; however, any attempt to dissect along the interface between Toldt fascia and the overlying mesocolon or underlying retroperitoneum failed. Within the anatomic territory of kidney, Toldt fascia fused with Gerota fascia, and then extended in all directions: upward to the dosal surface of the duodenum, liver and pancreas; medially to fuse with the adventitia layer of the abdominal aorta; laterally, it tapered at the area below the reflection of visceral and parietal peritoneum; and downward, it became a thin membranous structure covering the gonadal vessels, ureters and retroperitoneal structures and ended at the upper rectum, where it met the junction of endopelvic fascia and proper fascia of the rectum. The present study demonstrated that Toldt fascia is a natural embryonic dissection plane for the precise conduction of complete mesocolic excision for colon cancer.
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http://dx.doi.org/10.1016/j.asjsur.2018.11.006DOI Listing
January 2019

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer.

Oncology 2019 12;96(3):156-163. Epub 2018 Dec 12.

Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan,

Objective: We aimed to study the prognostic role of CpG island methylator phenotype (CIMP) in patients with different stages of colorectal cancer (CRC).

Material And Methods: We analyzed CIMP in stage I-IV CRC specimens from patients who were diagnosed between 2005 and 2013. CIMP status was determined using a 5-gene MethyLight-based assay. The clinicopathologic characteristics were reviewed and the overall survival (OS) was compared between patients with CIMP-high CRC and those with CIMP-low/negative CRC.

Results: Among 450 CRC specimens with successfully determined CIMP statuses, 74 (16.4%) were CIMP-high CRC. Although there was no difference in OS between patients with CIMP-high and CIMP-low/negative CRC across all stages (p = 0.4526), intriguingly, patients with stage IV CIMP-high CRC had significantly worse OS than those with stage IV CIMP-low/negative CRC (p = 0.0047). In a multivariate analysis, CIMP status remained an independent prognostic factor for overall mortality (HR = 5.60, 95% CI: 2.12-14.79, p = 0.0005) in metastatic CRC after adjusting for clinicopathologic variables and anti-cancer therapies.

Conclusion: Our results revealed that the presence of CIMP independently predicts poor OS in patients with stage IV CRC.
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http://dx.doi.org/10.1159/000493387DOI Listing
March 2019

Robotic Radical Surgery in the Multidisciplinary Approach for the Treatment of Locally Advanced T4 Rectosigmoid Colon Cancer.

Dis Colon Rectum 2019 01;62(1):121-122

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.1097/DCR.0000000000001253DOI Listing
January 2019

Three Nurse-administered Protocols Reduce Nutritional Decline and Frailty in Older Gastrointestinal Surgery Patients: A Cluster Randomized Trial.

J Am Med Dir Assoc 2019 05 10;20(5):524-529.e3. Epub 2018 Nov 10.

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Institute for Aging Research, Hebrew Senior Life, Boston, Massachusetts.

Objective: To evaluate the effects of the modified Hospital Elder Life Program (mHELP) comprising 3 nurse-administered protocols in older patients undergoing gastrointestinal (GI) surgery.

Design: Cluster randomized trial.

Setting: Two 36-bed GI wards at a university-affiliated medical center in Taiwan.

Participants: Older patients (≥65 years, N = 377) were recruited if they were scheduled for elective GI surgery with an expected length of hospital stay >6 days. After transferring to the GI ward after surgery, participants were randomly assigned to the mHELP or control group (1:1) by room rather than individually because most patient units are double- or triple-occupancy rooms.

Intervention: The mHELP protocols (early mobilization, oral and nutritional assistance, and orienting communication) were administered daily with usual care by a trained nurse until hospital discharge. The control group received usual care only.

Measures: Outcomes were in-hospital nutritional decline, measured by body weight and Mini-Nutritional Assessment (MNA) scores, and Fried's frailty phenotype. Return of GI motility was examined as a potential mechanism contributing to observed outcomes.

Results: Participants (mean age = 74.5 years; 56.8% male) primarily underwent colorectal (56.5%), gastric (21.2%), and pancreatobiliary (13.8%) surgery. Participants who received the mHELP [for a median of 7 days (interquartile range = 6-10 days)] had significantly lower in-hospital weight loss and decline in MNA scores (weight -2.1 vs -4.0 lb, P = .002; score -3.2 vs -4.0, P = .03) than the control group. The mHELP group also had significantly lower rates of incident frailty during hospitalization (12.0% vs 21.7%, P = .022), and persistent frailty (50.0% vs 92.9%, P = .03). Participants in the mHELP group had trends toward an accelerated return of GI motility.

Conclusion And Implications: The mHELP effectively reduced nutritional decline, prevented new frailty, and promoted recovery of frailty present before admission. These nurse-administered protocols might be useful in other settings, including conditions managed at home or in nursing facilities.
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http://dx.doi.org/10.1016/j.jamda.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607892PMC
May 2019

Robotic-assisted right posterior segmentectomies for liver lesions: single-center experience of an evolutional method in left semi-lateral position.

J Robot Surg 2019 Apr 11;13(2):231-237. Epub 2018 Jul 11.

Department of Surgery, National Taiwan University Hospital, College of Medicine, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan.

Despite the popularity of minimally invasive surgery (MIS) for hepatectomy, limitations in the approach of the right posterior section of the liver remain. Although skills and approach techniques have been developed for hepatectomy of lesions in the posterior segments of the liver, most are performed laparoscopically and are limited to few experienced hands using rigid laparoscopic instruments. In this study, we tried a different approach area via the aid of a flexible robotic system. Since 2012, we have successfully completed more than 200 robotic hepatectomy procedures in our institution. Two different patient settings have been applied for right posterior segment lesions, including supine position as general setting in early cases and left semi-lateral decubitus setting in our later cases. The demographic data and perioperative outcomes between the two groups were analyzed in regard to different positioning. A total of 25 patients with right posterior segment lesions underwent robotic-assisted resection, 13 were placed in supine position and 12 in left semi-lateral position. The left semi-lateral group had significantly shorter operation time (306.0 versus 416.8 min, p = 0.023), less blood loss (203.9 versus 1092.3 mL, p = 0.030), and lower transfusion rates (0 versus 46.2%, p = 0.015). We described an evolutionary technique for robotic right posterior segmentectomies with the patient placed in left semi-lateral position. This method can be applied for most patients easily and is demonstrated as a safe and feasible approach in selected patients owing to its ability to overcome the difficulty of MIS hepatectomy for right posterior lesions.
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http://dx.doi.org/10.1007/s11701-018-0842-1DOI Listing
April 2019

Should Surgical Treatment Be Provided to Patients with Colorectal Cancer Who Are Aged 90 Years or Older?

J Gastrointest Surg 2018 11 25;22(11):1958-1967. Epub 2018 Jun 25.

Division of Colorectal Surgery, Department of Surgery, Taipei University Shuang-Ho Hospital, Taipei City, Taiwan.

Purpose: The number of patients aged ≥ 90 years is increasing worldwide; however, the treatment guidelines for colorectal cancer in elderly patients remain unclear. This study aimed to investigate the clinical outcomes of patients with primary colorectal cancer aged ≥ 90 years.

Methods: We retrospectively reviewed the medical records of 100 patients (aged ≥ 90 years) with primary colorectal adenocarcinoma. Their demographic and clinical characteristics and surgical outcomes were assessed.

Results: The patients who underwent tumor resections (n = 71) showed longer overall and cancer-specific survival than those who underwent non-operative treatments (n = 29) (median overall survival time: 23.92 months vs. 2.99 months, P < 0.0001). Age, body mass index, performance status, advanced cancer stage (stages 3 and 4), and treatment strategy were identified as risk factors, prognostic factors, and predictors of overall survival. No significant differences in the postoperative morbidity rate, in-hospital mortality rate, and survival time were found between the elective laparoscopic (n = 27) and elective open (n = 37) surgery subgroups. However, the in-hospital mortality rate was 6.25% (4/64) in the patients who underwent elective open surgeries and 42.9% (3/7) in those who underwent emergent open surgeries (p = 0.0179).

Conclusions: In clinical practice, surgical treatment should not be denied to patients with primary colorectal cancer aged ≥ 90 years. However, the high complication and mortality rates for emergency surgeries act as a deterrent. Further studies to eliminate the bias between operative and non-operative groups may be needed to validate our results.
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http://dx.doi.org/10.1007/s11605-018-3843-5DOI Listing
November 2018

Pneumatosis cystoides intestinalis.

Asian J Surg 2018 01 19;41(1):98. Epub 2017 Dec 19.

Division of Colorectal Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taiwan.

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http://dx.doi.org/10.1016/j.asjsur.2017.11.001DOI Listing
January 2018

Revisiting Toldt Fascia Through Robotic Top-down and Medial-to-lateral Apporach - Video Vignette.

Colorectal Dis 2017 Dec 19. Epub 2017 Dec 19.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

In this video (Toldt fascia.wmv), we demonstrated anatomic features of Toldt fascia, based on the meticulous dissection and high-resolution images inherent in robotic surgery. Toldt fascia is sandwiched by the overlying mesothelial layer of the mesocolon and underlying mesothelial layer of the retroperitoneum, comprised loose fibrous tissues with minute vessels inside, and is contiguous from the ileocecal mesentery radix to the upper rectum. The medial-to-lateral surgical dissection plane is readily developed within the Toldt fascia; however, any attempt to dissect along the interface between Toldt fascia and the overlying mesocolon or underlying retroperitoneum failed. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/codi.13995DOI Listing
December 2017

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

Oncotarget 2017 Nov 10;8(60):101832-101846. Epub 2017 Oct 10.

Department of Radiation Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Background: To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT).

Method: A retrospective study was performed in 124 consecutive patients with clinically TNM-staged rectal cancer incorporating targeted agents in CCRT.

Results: Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p<0.0001), as evaluated by morphologic grading of hepatic steatosis and sinusoidal dilatation in laparoscopy. In the 57 patients with morphologically severe liver toxicity, 36 (63.2%) retained a normal liver function; for the remaining 21 patients with an abnormal liver function, the abnormality was self-limited in 19 patients, whereas 2 cetuximab-treated patients progressed to hepatic failure and mortality. A subset analysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes.

Conclusions: The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for TNM-staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.
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http://dx.doi.org/10.18632/oncotarget.21762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731917PMC
November 2017

Revisiting Rectosacral and Waldeyer's Fascia by Laparoscopic or Robotic Approach - Video Vignette.

Colorectal Dis 2017 Dec 15. Epub 2017 Dec 15.

Division of Colorectal Surgery Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

During the clinical practice of total mesorectal excision (TME) for the treatment of middle and low rectal cancer, posterior mobilisation of the rectum is along the holy plane, which consists of loose areolar connective tissues [1]. With further posterior downward mobilisation, a thick tough fascia will be encountered, generally known as rectosacral fascia, and failure to recognise and divide the rectosacral fascia can perforate the mesorectum or lead to severe presacral haemorrhage. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/codi.13993DOI Listing
December 2017

Adjunctive use of chromoendoscopy may improve the diagnostic performance of narrow-band imaging for small sessile serrated adenoma/polyp.

J Gastroenterol Hepatol 2018 Feb;33(2):466-474

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background And Aim: Endoscopic diagnosis of sessile serrated adenoma/polyp (SSA/P) is challenging because of their subtle appearance. Narrow-band imaging (NBI) is useful for diagnosis, but its utility with concurrent chromoendoscopy (CE), especially to detect small SSA/P, is unproven.

Methods: This prospective study enrolled 367 consecutive patients who underwent screening colonoscopy with the finding of serrated polyps. Patients were divided into derivation and validation cohorts: Diagnostic criteria using different endoscopic modalities were generated by regression analysis in the derivation cohort and were validated in the validation cohort for sensitivity, specificity, and accuracy.

Results: There were 180 patients with 119 SSA/P and 147 hyperplastic polyps (HP) in the derivation cohort and 187 patients with 177 SSA/P and 125 HP in the validation cohort. With white-light endoscopy plus NBI, mucus cap, surface grooves, and expanded crypt were most associated with SSA/P. With white-light endoscopy plus CE, II-O pit pattern, mucus cap, and superficial telangiectasia were most associated with SSA/P. With the combined use of these three modalities, II-O pit pattern, mucus cap, and surface grooves were most associated with SSA/P. For large serrated polyp, NBI in combination with CE had a better accuracy than NBI alone (91% vs 86%, P = 0.025) to distinguish SSA/P from HP. CE alone had a better accuracy than NBI alone for distinguishing small SSA/P from small HP (85% vs 72%, P < 0.0001).

Conclusion: Compared with NBI alone, adjunctive use of CE can improve the diagnostic accuracy for distinguishing SSA/P from HP, especially for small SSA/P.
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http://dx.doi.org/10.1111/jgh.13863DOI Listing
February 2018

Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial.

JAMA Surg 2017 Sep;152(9):827-834

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Importance: Older patients undergoing abdominal surgery commonly experience preventable delirium, which extends their hospital length of stay (LOS).

Objective: To examine whether a modified Hospital Elder Life Program (mHELP) reduces incident delirium and LOS in older patients undergoing abdominal surgery.

Design, Setting, And Participants: This cluster randomized clinical trial of 577 eligible patients enrolled 377 older patients (≥65 years of age) undergoing gastrectomy, pancreaticoduodenectomy, and colectomy at a 2000-bed urban medical center in Taipei, Taiwan, from August 1, 2009, through October 31, 2012. Consecutive older patients scheduled for elective abdominal surgery with expected LOS longer than 6 days were enrolled, with a recruitment rate of 65.3%. Participants were cluster randomized by room to receive the mHELP or usual care.

Interventions: The intervention (implemented by an mHELP nurse) consisted of 3 protocols administered daily: orienting communication, oral and nutritional assistance, and early mobilization. Intervention group participants received all 3 mHELP protocols postoperatively, in addition to usual care, as soon as they arrived in the inpatient ward and until hospital discharge. Adherence to protocols was tracked daily.

Main Outcomes And Measures: Presence of delirium was assessed daily by 2 trained nurses who were masked to intervention status by using the Confusion Assessment Method. Data on LOS were abstracted from the medical record.

Results: Of 577 eligible patients, 377 (65.3%) were enrolled and randomly assigned to the mHELP (n = 197; mean [SD] age, 74.3 [5.8] years; 111 [56.4%] male) or control (n = 180; mean [SD] age, 74.8 [6.0] years; 103 [57.2%] male) group. Postoperative delirium occurred in 13 of 196 (6.6%) mHELP participants vs 27 of 179 (15.1%) control individuals, representing a relative risk of 0.44 in the mHELP group (95% CI, 0.23-0.83; P = .008). Intervention group participants received the mHELP for a median of 7 days (interquartile range, 6-10 days) and had a shorter median LOS (12.0 days) than control participants (14.0 days) (P = .04).

Conclusions And Relevance: For older patients undergoing abdominal surgery who received the mHELP, the odds of delirium were reduced by 56% and LOS was reduced by 2 days. Our findings support using the mHELP to advance postoperative care for older patients undergoing major abdominal surgery.

Trial Registration: clinicaltrials.gov Identifier: NCT01045330.
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http://dx.doi.org/10.1001/jamasurg.2017.1083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710459PMC
September 2017

Robotic major hepatectomy: Is there a learning curve?

Surgery 2017 03 22;161(3):642-649. Epub 2016 Nov 22.

Department of Surgery, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Background: Robotic hepatectomy has been suggested as a safe and effective management of liver disease. However, no large case series have documented the learning curve for robotic major hepatectomy.

Method: We conducted a retrospective study for robotic major hepatectomy performed by the same operative team between January 2012 and October 2015 and evaluated the learning curve for operation time using the cumulative sum method, presented as cumulative sum.

Results: Overall, there were 183 robotic hepatectomies, 92 of which were performed in patients who underwent robotic major hepatectomy: left hemihepatectomy was performed in 32 (34.8%) patients, right hemihepatectomy in 41 (44.6%), left trisectionectomy in 3 (3.3%), right trisectionectomy in 6 (6.5%), and 8-5-4 trisegmentectomy in 10 (10.8%). The median duration of surgery was 434 minutes (142-805 minutes) and the median blood loss was 195 mL (50-2,000 mL). Fifty-nine percent of patients had malignancies, and those with advanced stages of cancer had more blood loss during an operation. The cumulative sum model of robotic major hepatectomy suggested that the learning curve comprised 3 characteristic phases: initial (phase 1, 15 patients), intermediate (phase 2, 25 patients), and mature (phase 3, 52 patients). The learning effects were underlined by shorter operation time and hospital stay after phase 1 and less blood loss after phase 2.

Conclusion: This is the largest series regarding robotic major hepatectomy. Our findings suggest that a solid training program based on the learning curve should be considered for beginners of robotic hepatectomy. Participants should evaluate the evolution of our minimally invasive hepatectomy before considering our robotic experience.
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http://dx.doi.org/10.1016/j.surg.2016.09.025DOI Listing
March 2017

Robotic Versus Open Hepatectomy for Hepatocellular Carcinoma: A Matched Comparison.

Ann Surg Oncol 2017 Apr 24;24(4):1021-1028. Epub 2016 Oct 24.

Department of Surgery, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan.

Background: Robotic hepatectomy has been suggested to be a safe and effective approach for liver disease; however, studies comparing robotic hepatectomy with the conventional open approach regarding oncologic outcomes for hepatocellular carcinoma (HCC) are limited. Accordingly, we performed a matched comparison of surgical and oncological outcomes between robotic and open hepatectomy.

Methods: Between January 2012 and October 2015, a total of 183 patients underwent robotic hepatectomy and 275 patients underwent open hepatectomy by the same surgical team in our center. Eighty-one newly diagnosed HCC cases in each group were compared under propensity score matching (PSM) in a 1:1 ratio.

Results: With robotic hepatectomy, the conversion rate was 1.6 % and the complication rate was 4.4 %. On PSM, the groups had a comparable percentage of major liver resections (41.9 vs. 39.5 %) and liver cirrhosis (45.7 vs. 46.9 %). Compared with the open group, the robotic group required longer operation times (343 vs. 220 min), shorter hospital stays (7.5 vs. 10.1 days), and lower dosages of postoperative patient-controlled analgesia (350 vs. 554 ng/kg). The 3-year disease-free survival of the robotic group was comparable with that of the open group (72.2 % vs. 58.0 %; p = 0.062), as was the 3-year overall survival (92.6 vs. 93.7 %; p = 0.431).

Conclusions: This is the first oncological study comparing robotic liver resection for HCC with open resection. Robotic hepatectomy can be applied for challenging major resections in patients with cirrhotic liver disease with less postoperative pain and shorter hospital stays without compromising oncological outcomes.
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http://dx.doi.org/10.1245/s10434-016-5638-9DOI Listing
April 2017

Fecal Immunochemical Test Detects Sessile Serrated Adenomas and Polyps With a Low Level of Sensitivity.

Clin Gastroenterol Hepatol 2017 Jun 4;15(6):872-879.e1. Epub 2016 Aug 4.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Health Management Center, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Background & Aims: The serrated pathway is a distinct pathway of colorectal carcinogenesis that has been implicated in development of a substantial proportion of interval colorectal cancers. The fecal immunochemical test (FIT) detects early neoplasms with a higher level of sensitivity than the guaiac test. We investigated the sensitivity of the FIT in detection of sessile serrated adenomas/polyps (SSA/Ps).

Methods: We performed a prospective study of 6198 asymptomatic subjects (mean age, 59.0 ± 7.0 years) who received concurrent screening colonoscopies and FITs at the Health Management Center of National Taiwan University Hospital from August 2010 through November 2014. The sensitivity of FIT for conventional adenoma, advanced adenoma, and SSA/P at different cutoffs was calculated, and results were compared by using multivariate analysis adjusted for potential confounders.

Results: Prevalence values of SSA/P, adenoma, and advanced adenoma were 1.4%, 20.2%, and 5.5%, respectively. At cutoffs of 10, 15, and 20 μg hemoglobin/g feces, the FIT detected all SSA/Ps with 12.3%, 6.2%, and 6.2% sensitivity, large SSA/Ps with 18.4%, 10.5%, and 10.5% sensitivity, and advanced adenomas with 32.4%, 24.5%, and 20.9% sensitivity, respectively. Multivariate analysis revealed that positive results from the FIT did not differ significantly between individuals with SSA/P and those with non-advanced adenoma or those with negative findings from colonoscopy. Patients with large SSA/Ps were less likely to have positive results from the FIT than patients with advanced adenoma, with odds ratios of 0.44 (95% confidence interval [CI], 0.18-1.05), 0.30 (95% CI, 0.10-0.90), and 0.37 (95% CI, 0.12-1.12) at cutoffs of 10, 15, and 20 μg hemoglobin/g feces, respectively, after adjusting for lesion size, even with synchronous conventional adenoma.

Conclusions: In a prospective study of 6198 subjects receiving the FIT and colonoscopy, we found that the FIT detected SSA/Ps with significantly lower levels of sensitivity than conventional adenoma. Further studies are needed to determine the effects of these findings on the effectiveness of FIT-based colorectal cancer screening program.
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http://dx.doi.org/10.1016/j.cgh.2016.07.029DOI Listing
June 2017

Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Histone Deacetylase as a Therapy for Colorectal Cancer.

EBioMedicine 2016 Aug 17;10:124-36. Epub 2016 Jul 17.

Department of Pharmacology, National Taiwan University College of Medicine, Taipei 100, Taiwan. Electronic address:

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) inhibitors decreasing serum cholesterol and have shown promise in cancer prevention. In this study, we demonstrated the oncogenic role of HMGR in colorectal cancer (CRC) by disclosing increased HMGR activity in CRC patients and its enhancement of anti-apoptosis and stemness. Our previous studies showed that statins containing carboxylic acid chains possessed activity against histone deacetylases (HDACs), and strengthened their anti-HDAC activity through designing HMGR-HDAC dual inhibitors, JMF compounds. These compounds exerted anti-cancer effect in CRC cells as well as in AOM-DSS and Apc(Min/+) CRC mouse models. JMF mostly regulated the genes related to apoptosis and inflammation through genome-wide ChIP-on-chip analysis, and Ingenuity Pathways Analysis (IPA) predicted their respective regulation by NR3C1 and NF-κB. Furthermore, JMF inhibited metastasis, angiogenesis and cancer stemness, and potentiated the effect of oxaliplatin in CRC mouse models. Dual HMGR-HDAC inhibitor could be a potential treatment for CRC.
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http://dx.doi.org/10.1016/j.ebiom.2016.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006731PMC
August 2016

Laparoscopic En Bloc Resection of T4 Colon Cancer Invading the Spleen and Pancreatic Tail.

Dis Colon Rectum 2016 Jun;59(6):581-2

1 Division of Colorectal Surgery, Department of Surgery, Hsinchu Branch, National Taiwan University Hospital, Hsinchu, Taiwan 2 Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.1097/DCR.0000000000000584DOI Listing
June 2016

Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.

Cancer Nurs 2017 May/Jun;40(3):201-208

Author Affiliations: School of Nursing (Ms Chou, Drs Lai and Shun), College of Medicine, National Taiwan University; and Department of Surgery (Drs Lin and Liang), National Taiwan University Hospital, Taipei, Taiwan.

Background: Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise.

Objectives: The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors.

Methods: A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise.

Results: Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant.

Conclusions: Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered.

Implications For Practice: Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.
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http://dx.doi.org/10.1097/NCC.0000000000000383DOI Listing
August 2017