Introduction

FOLFIRINOX and Gemcitabine/Nab-paclitaxel are widely used 1st-line regimens in metastatic pancreatic cancer. We would like to present real-world data of 12 years of experience with both regimens including genomics insights

Aims & Methods

Patients with metastatic pancreatic cancer who received FOLFIRINOX or Gemcitabine/Nab-paclitaxel were retrospectively included from January 2010 to December 2022. Outcomes were overall survival (OS) and progression free survival (PFS). Median survival time was calculated using Kaplan-Meier estimates adjusted with 1:1 Propensity Score Matching (PSM). Additional tissue Next Generation Sequencing (NGS) panel data was analyzed.

Results

A total of 521 patients, 251 patients received FOLFIRINOX and 270 patients received Gemcitabine/Nab-paclitaxel as a first-line regimen. FOLFIRINOX group were younger (61.8 vs. 65.9, p <0.001). Before PSM, FOLFIRINOX group showed prolonged median OS (11.1 vs 7.8 months) and PFS (8.8 vs. 5.8 months) ( p = 0.002, both) compared to Gemcitabine/Nab-paclitaxel group. After PSM, FOLFIRINOX group still showed prolonged median OS (11.1 vs 9.0 months, p = 0.010) and PFS (9.2 vs 6.4 months, p = 0.001) than Gemcitabine/Nab-paclitaxel group. NGS was available from 31 and 22 patients in the FOFLIRINOX and Gemcitabine/Abraxane group, respectively. The most frequently mutated genes were KRAS (94.3%), TP53 (84.9%), CDKN2A (24.5%), SMAD4 (24.5%), ARID1A(13.2%) and RNF43(9.4%). On Cox Regression Analysis, RNF43 mutation was correlated with poor PFS with Gemcitabine/Nab-paclitaxel (HR, 4.849; 95% CI, 1.150-20.450, P= 0.032).

	FOLFIRINOX (N = 31)			Gemcitabine/Nab-P (N = 22)
	cHR	95% CI	P value	cHR	95% CI	P value​
KRSA	2.577	0.597-11.115	0.204	1.602	0.209-12.279	0.650
TP53	1.922	0.576-6.414	0.288	1.122	0.363-3.464	0.842
CDKN2A	1.698	0.708-4.074	0.236	1.103	0.409-2.973	0.846
SMAD4	0.678	0.274-1.677	0.400	0.701	0.264-1.860	0.475
ARID1A	0.670	0.158-2.848	0.588	1.919	0.610-6.034	0.265
RNF43	1.199	0.276-5.210	0.809	4.849	1.150-20.450	0.032
cHR, Crude hazard ratio; CI, confidence interval

Conclusion

FOLFIRINOX showed prolonged OS and PFS compared to Gemcitabine/Nab-paclitaxel. FOLFIRINOX can be considered 1st-line regimen in metastatic disease. The NGS data suggest RNF43 could be a potential predictive marker for the response to Gemcitabine/Nab-Paclitaxel, however, larger size confirmation study is needed to validate this finding.

Introduction

Rigid surgical instruments used for conventional laparoscopic surgery provide limited movement, and it is difficult to perform skillful surgery due to their long, jointless straight features. Articulated instruments could have the same advantages seen in robotic surgery, such as excellent control in smaller spaces, restoration of more intuitive and ergonomic movements, and the ability to overcome obstacles on a direct visual line. The aim of this study was to evaluate the surgical performance and clinical outcomes of patients following laparoscopic colorectal surgery with multijoint laparoscopic instruments, ArtiSential® (LivsMed, Seongnam, Korea), compared with those using conventional instruments.

Aims & Methods

Patients aged 19–80 years undergoing elective laparoscopic surgery for colorectal disease between December 2021 and November 2022, were consecutively enrolled. The first 20 cases underwent conventional laparoscopic surgery, and the latter 50 cases underwent laparoscopic surgery using ArtiSential®. Unedited operative videos were submitted to the Crowd-Sourced Assessment of Technical Skills (C-SATS) platform for evaluation using the Global Operative Assessment of Laparoscopic Skills (GOALS), which is a validated tool for technical proficiency. Each of GOALS’ four domains (bimanual dexterity, depth perception, efficiency, and tissue handling) was scored on a Likert scale between 1 and 5, scoring anchor, with a total score ranging from 4 to 20. The learning curve analysis was performed using the cumulative sum control chart (CUSUM) for GOALS grades (Registration number: KCT0006798).

Results

There was no significant difference between group with regards to type of operation, hospital stay, and 30-day postoperative complication. The GOALS’ grades were similar between the two groups (15.7 ± 0.7 vs. 15.9 ± 0.5, P = 0.190), but the scores in two domains (depth perception and tissue handling) were significantly higher in the ArtiSential® group (3.9 ± 0.3 vs. 4.0 ± 0.2, P = 0.014 and 3.9 ± 0.2 vs. 4.1 ± 0.2, P = 0.048, respectively) compared with those in the conventional group. In addition, patients in the ArtiSential® group experienced a shorter operation time (122.3 ± 58.9 vs. 88.1 ± 35.1, P = 0.022) and less intraoperative blood loss (56.5 ± 69.9 vs. 29.8 ± 1.4, P = 0.002) than those in the conventional group. According to the CUSUM learning curve analysis, the first 10 cases using ArtiSential® were in the inexperienced phase, and the remaining 40 cases were in the experienced phase. The GOALS’ score in the experienced phase of ArtiSential® was improved compared with that in the conventional group (16.0 ± 0.5 vs. 15.7 ± 0.7, P = 0.037).

Conclusion

A plateau in the learning curve of laparoscopic colorectal surgery performed with an articulated instrument was observed in approximately 10 cases, and it can be expected that surgical proficiency in the experienced phase increases without deterioration of clinical outcome as compared to that in conventional surgery.

References

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Disclosure

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grantnumber: HI20C2092).

Introduction

Endoscopic full thickness resection (EFTR) of the colon has been described as an effective practicable method for resection of recurrent /advanced neoplastic lesions, but its performance and success may be difficult or different according to location of the lesion in the corresponding colonic segment.
The aim was to investigate the segment-specific efficacy and safety of EFTR in the colon using a full thickness resection device (FTRD) from real-world data.

Aims & Methods

EFTR was conducted in patients being referred to either of the 4 participating centers after previous colonoscopy leading to a diagnosis suitable for EFTR. The primary efficacy measure of EFTR was histologically complete resection (R0) of the lesion. Safety was investigated considering the frequency of adverse events (AE) to EFTR occurring during the procedure or afterwards.

Results

105 patients (66m/39f; median 70yrs) were included in the analysis. FTRD was technically successful in 101 patients (96.2%) with a median lesion size of 20 x 19mm (15-24).
Histologically R0 resection was obtained in 77.1% of the patients with a segment-specific range from 90% (rectum), 70.6% sigmoid, 78.6% descending colon to 62.5% (transverse colon), while in ascending colon and cecum resection rates of 76.9 and 83.3% could be achieved.
Overall, adverse event rate (AE, any) were documented in 33 patients (31.4%), with only 1 perforation in sigmoid (0.95%), while the others were minor, abdominal postsurgical pain (18.1%), hematochezia (9.5%), and haemoglobin decline (7.6%). Topographical analysis revealed that AE were most attributable to transverse colon (12.5%), while in the other segments AE were each lower or equal than 8.2%; the lowest rate of AE was found in rectum with 1.4%.

Conclusion

EFTR is efficacious for the endoscopic treatment of colorectal lesions with best outcome parameters in rectum (high R0 rate, low AE), followed by cecum. The other segments appeared to be more difficult for complete resection and showed a higher AE rate. Transverse colon was identified with lowest R0 resection rates and highest frequency of AE. While only one major complication occurred, minor complications in all other segments were below 8.2% and short-lived.

Introduction

Post surgical fistulas of the upper digestive tract(UDT) are associated with significant morbidity and mortality. The indication for surgery may influence outcomes.

Aims & Methods

We aimed to evaluate the clinical presentation,efficacy and safety of a primarily endoscopic approach to management of post surgical fistula of the UDT comparing oncologic versus non-oncologic indications for surgery.

Multicentre retrospective analysis involving 126 consecutive patients who underwent primarily endoscopic management of post surgical fistulas of the UDT between March2009-January2022. Clinical efficacy (fistula closure) and adverse events in patients with fistulas after oncologic and non-oncologic surgery were compared.Qualitative variables were evaluated with Chi-square test. Quantitative variables with non-normal distribution were expressed as median(min-max) and evaluated with Mann-Whitney´s test. We performed logistic regression analysis to determine factors associated with fistula closure and adverse events. A p value <0.05 was considered statistically significant (IBM SPSS28).

Results

Median age was 57(17-89) years and 73(60%) patients were female. Indications for surgery were non-oncologic in 80 patients(63.5%) ((mostly bariatric, n=73)) and cancer in 46(36.5%) patients.
Patients undergoing oncologic surgery were older and with male predominance. There were no differences regarding median time to detect fistula or fistula size between the groups. Fever, abdominal pain and abdominal collections were more frequent in non-oncologic surgery group. On laboratory analysis, only haemoglobin was significantly lower in patients undergoing oncologic surgery(Table1). We found no significant difference on leukocyte count, neutrophil percentage, C-reactive protein, AST, ALT, total bilirubin, INR or creatinine.

		Oncologic	Non-oncologic	p-value
Characterization	Median age	71(52-89),	45(17-79)	<0.001
	Female gender	21(26%)	35 (76%)	<0.001
	Median time to fistula detection(days)	8(1-83)	6(1-387)	0.08
	Fistula size(mm)	5.0(2.0-25.0)	5.0(1.0-30.0)	0.671
Clinical presentation	Fever	18(39%)	49(61%)	0.049
	Abdominal pain	13(28%)	46(58%)	0.006
	Abdominal collections	11(n=24%)	48(60%)	<0.001
	Sepsis	13(n=28)	21(26%)	0.309

Endoscopic interventions were similar in both groups and included placement of a covered metallic stent in 64(80.0%) non-oncologic patients and 34(73.9%) oncologic patients (p=0.506) and clips in 99(48.8%) oncologic patients and 19(41.3%) (p=0.461) non-oncologic patients. The frequency of early adverse events (<1 week) (8(17%) vs 14(18%), p=1.0),as well as late adverse events (10(22%)vs 21(26%), p=0.670) were similar in both groups
We documented clinical success (fistula closure) in 72(90%) of non-oncologic patients and 34(74%, p=0.023) of oncologic patients, but after a similar median duration of management (13 (1-423) weeks vs 6(1-55) weeks, p=0.11) and number of endoscopies (3(1-8) vs 2(1-13), p=0.706).
After a median follow up of 36(1-147) and 12.5(1-113) months, 6(7.5%) and 28(60.9%) patients died, respectively from the group of non-oncologic and oncologic surgery. In the oncologic surgery group, 12 patients (48%) died from progression of oncologic disease.

Conclusion

A primarily endoscopic approach is effective in >70% of patients with fistulas after UDT surgery but it´s efficacy was significantly lower in patients with fistulas after oncologic surgery compared to non-oncologic surgery and this may have been due to the higher age and male predominance.

Introduction

Stenosis after esophageal Endoscopic Submucosal Dissection (ESD) has a high incidence of ranks, and muscular injury might be an important risk factor for esophageal stenosis.

Aims & Methods

Our study aimed to classify muscular injury degree and investigate its association with postoperative stenosis. This retrospective study included 1,033 patients with esophageal mucosal lesions treated by ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and further used to investigate the association between the different degrees of muscular injury and postoperative stenosis. Finally, a scoring system was established for the prediction of muscular injury.

Results

Of 1,033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with Type II muscular injuries tended to develop complex stenosis (n = 13, 36.1%, p < 0.05). Moreover, Type II muscular injuries were more likely to predispose patients to severe stenosis than Type I (73.3 and 92.3%, respectively). According to the scoring system for predicting muscular injury, patients with high scores (3-6) were more likely to suffer muscular injury. The score model presented good discriminatory power in the internal validation (AUC: 0.706; 95% CI: 0.645-0.767) and goodness-of-fit in the Hosmer-Lemeshow test (p = 0.865).

Conclusion

Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

References

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