Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma.

BACKGROUND: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC in 2000-2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. RESULTS: Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. CONCLUSION: The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.

BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

Surgical management of disappearing colorectal liver metastases.

BACKGROUND: Owing to expanded surgical indications for colorectal liver metastasis (CRLM) and improved systemic therapy, hepatic surgeons are increasingly faced with the problem of disappearing (no longer visible on imaging) liver metastasis (DLM). METHODS: A review of relevant studies was performed. Studies that reported on DLM associated with preoperative chemotherapy for CRLM were identified, and data were synthesized and tabulated. The PubMed database was searched for relevant articles published between January 2000 and December 2012. RESULTS: A complete response on imaging does not necessarily equate with a complete clinical or pathological response. Rather, residual macroscopic disease is found in about 25-45 per cent of patients at the time of operation. Even among patients with a complete pathological response, long-term remission occurs in only 20-50 per cent of those treated with systemic therapy. A durable response of DLM is more common following the use of hepatic artery infusion therapy. CONCLUSION: Liver resection should include all original sites of disease if possible.

Simulated laparoscopy using a head-mounted display vs traditional video monitor: an assessment of performance and muscle fatigue.

BACKGROUND: The direction of visual gaze may be an important ergonomic factor that affects operative performance. We designed a study to determine whether a head-mounted display (HMD) worn by the surgeon would improve task performance and/or reduce muscle fatigue during a laparoscopic task when compared to the use of a traditional video monitor display (VMD). METHODS: Surgical residents (n = 30) were enrolled in the study. A junior group, consisting of 15 postgraduate year (PGY) = 1 subjects with no previous laparoscopic experience, and a senior group, consisting of 15 PGY 4 and PGY 5 subjects with experience, completed a laparoscopic task that was repeated four times using the Computer Enhanced Laparoscopic Training System (CELTS). Groups alternated between using the HMD with the task placed in a downward frontal position and the VMD with the task at a 30 degrees lateral angle. The CELTS module assessed task completion time, depth perception, path length of instruments, response orientation, motion smoothness; the system then generated an overall score. Electromyography (EMG) was used to record sternocleidomastoid muscle activity. Display preference was surveyed. RESULTS: The senior residents performed better than the junior residents overall on all parameters (p < 0.05) except for motion smoothness, where there was no difference. In both groups, the HMD significantly improved motion smoothness when compared to the VMD (p < 0.05). All other parameters were equal. There was less muscle fatigue when using the VMD (p < 0.05). We found that 66% of the junior residents but only 20% of the senior residents preferred the HMD. CONCLUSIONS: The CELTS module demonstrated evidence of construct validity by differentiating the performances of junior and senior residents. By aligning the surgeon's visual gaze with the instruments, HMD improved smoothness of motion. Experienced residents preferred the traditional monitor display. Although the VMD produced less muscle fatigue, inexperienced residents preferred the HMD, possibly because of improved smoothness of motion.

Computer-enhanced laparoscopic training system (CELTS): bridging the gap.

BACKGROUND: There is a large and growing gap between the need for better surgical training methodologies and the systems currently available for such training. In an effort to bridge this gap and overcome the disadvantages of the training simulators now in use, we developed the Computer-Enhanced Laparoscopic Training System (CELTS). METHODS: CELTS is a computer-based system capable of tracking the motion of laparoscopic instruments and providing feedback about performance in real time. CELTS consists of a mechanical interface, a customizable set of tasks, and an Internet-based software interface. The special cognitive and psychomotor skills a laparoscopic surgeon should master were explicitly defined and transformed into quantitative metrics based on kinematics analysis theory. A single global standardized and task-independent scoring system utilizing a z-score statistic was developed. Validation exercises were performed. RESULTS: The scoring system clearly revealed a gap between experts and trainees, irrespective of the task performed; none of the trainees obtained a score above the threshold that distinguishes the two groups. Moreover, CELTS provided educational feedback by identifying the key factors that contributed to the overall score. Among the defined metrics, depth perception, smoothness of motion, instrument orientation, and the outcome of the task are major indicators of performance and key parameters that distinguish experts from trainees. Time and path length alone, which are the most commonly used metrics in currently available systems, are not considered good indicators of performance. CONCLUSION: CELTS is a novel and standardized skills trainer that combines the advantages of computer simulation with the features of the traditional and popular training boxes. CELTS can easily be used with a wide array of tasks and ensures comparability across different training conditions. This report further shows that a set of appropriate and clinically relevant performance metrics can be defined and a standardized scoring system can be designed.