R0 Resection Margin Research Articles

Hepatic Arterial Variations and Its Implication During Pancreatic Cancer Surgeries.

Aberrant hepatic artery anatomy is a considerable challenge during pancreatic surgery as it warrants extreme caution for the preservation of vascular supply as well as achievement of R0 resection margin. We reviewed the literature about the aberrant anatomical variations of the hepatic artery and its relevance during pancreatoduodenectomy and distal pancreatectomy. Preoperative deliberation of peri-pancreatic vascular anatomy using advanced imaging methods is crucial for surgeons. At the same time, intra-operative suspicion and early identification of aberrant anatomy may help to prevent vascular injury and related complications. Yet, vascular reconstruction may be needed in many situations; several techniques like pre-operative embolization provide new options for management in specific situations. We have provided here an overview of the anatomical variants of the hepatic artery and their implicationduring pancreatoduodenectomy and distal pancreatectomy.

Robotic Versus Open Liver Resection in Hepatocarcinoma: Surgical and Oncological Outcomes.

Minimally invasive approaches are spreading in every field of surgery, including liver surgery. However, studies comparing robotic hepatectomy with the conventional open approach regarding oncologic outcomes for hepatocellular carcinoma are limited. We retrospectively reviewed demographics characteristics, pathologic features, surgical, and oncological outcomes of patients who underwent robotic and conventional open liver resection for hepatocellular carcinoma. No significant differences in demographics features, tumor size, tumor location, and type of liver resection were found. The morbidity rate was similar, 23% for the open group versus 17% of the robotic group (P=0.605). Perioperative data analysis showed a greater estimated blood loss in patients who underwent open resection, if compared with robotic group (P=0.003). R0 resection and disease-free resection margins showed no statistically significant differences. The 3-year disease-free survival of the robotic group was comparable with that of the open group (54% vs. 37%; P=0.592), as was the 3-year overall survival (87% vs. 78%; P=0.203). The surgical and the oncological outcomes seem to be comparable between minimally invasive and open hepatectomy. Robotic liver resections are effective, and do not compromise the oncological outcome, representing a reasonable alternative to the open approach.

Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer: A single center phase II trial.

69 Background: Chemoradiotherapy (CRT) remains the standard treatment choice for locally advanced rectal cancer (LARC). Neoadjuvant chemotherapy alone with doublet mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) seemed not to influence recurrence free survival with the advantage of less treatment-related complications. This phase II trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC (NCT03443661). Methods: Patients with LARC received up to 5 cycles of mFOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 were administered on Day 1, fluorouracil 2400 mg/m2 was administered as a continuous intravenous infusion for 48 hours on Day 1, and was repeated every 14 days). Magnetic resonance imaging (MRI) was performed to assess the baseline and post-chemotherapy TN stage. Radical resection was performed within 4–6 weeks of the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX (oxaliplatin and capecitabine) was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2, and positive circumferential resection margin (CRM). The primary endpoint was the pathological complete response (pCR) rate. Results: Between December 2015 to March 2019, a total of 50 patients were enrolled. 48 (96%) of the patients were clinically node-positive, 28 (56.5%) were CRMnvolved, and 39 (78.4%) were extramural venous invasion (EMVI)-positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range, 1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients achieved pathological node-negative status. The proportion of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively (table). Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or more toxicities included neutrocytopenia (50%), leukopenia (14%), and diarrhea (12%) during neoadjuvant chemotherapy. Clinical meaningful surgical morbidities included pneumonia (n=1), pelvic infection (n=1), and anastomotic fistula (n=1). With a median follow-up time of 33 months (range, 14–73 months), local recurrences and distant metastases were confirmed in 3 (6.5%) and 8 (17.4%) cases, respectively. Conclusions: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect with an ordinary pCR rate, and seemed effective in eliminating EMVI and transforming CRM-positive to CRM-negative status in patients with LARC. The preliminary survival results are promising. This regimen could serve as a potential alternative to CRT in selected patients with LARC. Clinical trial information: NCT03443661. [Table: see text]

Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study

Background: Extended resections (i.e. major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) as outcomes remain inconclusive. Little data is available from Western centers. In this Dutch, multicenter cohort study outcomes of patients who underwent extended resections for locally advanced GBC are analyzed. Design: Patients with GBC who underwent extended resection with curative intent from 2000 to 2018 were identified from the Netherlands Cancer Registry (NCR). Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments) and/or a pancreatoduodenectomy. Post-operative morbidity, mortality, survival and characteristics of short- and long-term survivors were assessed. Results: A total of 33 patients was included. R0-resection margins were achieved in 16 patients. Major post-operative complications (≥CD3A) occurred in 19 patients and post-operative mortality < 90 days in four. Recurrence occurred in 24 patients. Median overall survival (OS) was 12.8 months (95% CI 6.5 − 19.0). Two-year survival was achieved in 10 patients (30%) and 5-year survival in 5 patients (15%). Jaundice, common bile duct-, liver-, perineural- and perivascular invasion were associated with reduced survival. All (3) recurrence-free patients had R0 resection margins and no liver invasion. Conclusion: Median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although post-operative morbidity and mortality were significant, long term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival and a subgroup of patients benefit from surgery.Tabled 1Patient and operative characteristics of GBC patients that underwent extended resectionAge (IQR)64 (57- 69)Gender (male)13 (39%)ASA classification <319 (76%)Pre-operative biliary drainage (yes)20 (61%)Portal Vein Embolization performed5 (15%)Hepatectomy12 (36%)Extended hepatectomy7 21%)Hepatectomy + pancreatoduodenectomy2 (6%)Pancreatoduodenectomy + liver wedge resection21 (36%)Portal vein reconstruction10 (30%) Open table in a new tab

Laparoscopic vs. open pancreaticoduodenectomy: a single centre's initial experience with introduction of a novel surgical approach

Presenter: Evelyn Waugh MD | London Health Sciences Centre Background: The open method has been the standard approach to pancreaticoduodenectomy (PD and is associated with significant morbidity. Laparoscopic PD is posited to reduce postoperative length of stay (LOS) and perioperative complications while maintaining comparable oncological outcomes to open PD. While literature demonstrates a trend toward a benefit of laparoscopic PD, this technique remains in its early years and more evidence must be accumulated as the approach becomes more refined. As one of the few centres in Canada routinely performing laparoscopic PD, London Health Sciences Centre (LHSC) is in a unique position to describe the utilization of this novel technique within the Canadian healthcare system. Methods: Data were collected prospectively from patients undergoing laparoscopic PD between 2018 – 2020 for any elective indication. This timeframe encompasses introduction and early utilization of the technique. Data were reported using descriptive statistics. Primary outcomes include POPF rate, LOS, in-hospital complications, 30d morbidity and mortality, 30d readmission and 30d re-operation. Secondary outcomes include R0 resection and time to recurrence. This examines the chronological trend associated with uptake and early utilization of laparoscopic PD including rates of conversion to open and reasons for conversion. These outcomes were compared to NSQIP institutional and collaborative data for all PD cases. Results: 127 patients underwent PD between January 2018 and November 2020. 17 were completed either laparoscopically or laparoscopic-assisted. 41% (n = 7) of laparoscopic cases were converted to open. Two were planned conversions, one had portal venous involvement requiring vascular reconstruction, one required hand port insertion for specimen palpation, one patient had significant adhesions, one had significant tumour bulk impairing adequate visualization and one patient was difficult to ventilate with pneumoperitoneum. All patients undergoing laparoscopic PD had resectable tumours. Mean operative time was 6 hours 28 minutes. 53% (n=9) experienced Clavien-Dindo Grade III or higher post-operative complication. Median length of stay was 10 days. POPF occurred in 17.6% (n = 3) and were all IPGFS-B. 35% (n = 6) required 30d readmission. 17.6% (n = 3) required re-operation due to gastric outlet obstruction, failure of the hepaticojejunostomy causing GDA bleeding secondary to bile erosion and concomitant missed enterotomy, and erroneous cutting and intra-abdominal retraction of an external pancreatic causing abscess formation. There was one 30-day mortality due to out of hospital cardiac arrest with no evidence of intra-abdominal complication on autopsy. R0 resection margins were achieved in all specimens. No patients had early recurrence. Median follow-up was 92 days (range = 15 – 584). Conclusion: This study demonstrates the early experience of our institution with laparoscopic PD. While some cases required conversion to open due to patient factors, conversions that were either planned or due to difficult dissection occurred earlier in adoption of this technique indicating the presence of a technical learning curve. Postoperative morbidity, readmission and reoperation remains higher than NSQIP reported rates which may also be attributable to early introduction of this approach. Oncologic resection was achieved in all cases. Future directions include a propensity-matched comparison to open PD and ongoing analyses as the technique mature.

Image-Guidance for Non-Anatomical Liver Resections: An ex-vivo Study

Introduction: Non-anatomical resections of liver tumors are becoming more popular because they spare a larger portion of healthy liver parenchyma. However, the lack of anatomical landmarks to follow during the resection process makes them technically more challenging than anatomical resections. Image-guidance systems have been introduced to provide additional guidance, but are rarely used due to their inaccuracy, time-effort and complexity in usage and setup. Therefore, we have designed a new navigation approach that renders a surgical plan intra-operatively in real time using only navigated ultrasound. Method: The ultrasound based navigation approach comprises the following steps:i)scanning the surface using the navigated ultrasound,ii)marking the tumor location and size on a midsection ultrasound image,iii)specifying a resection shape and a safety margin to create an optimal surgical plan. In this study, we evaluated this method in an ex-vivo porcine model by three experienced hepatobiliary surgeons with respect to R0 resection status. Results: In 22 out of 23 resections an R0 resection (margin > 1mm) was achieved (95.7%) with a median resection margin of 5.9 mm (IQR 3.5 - 7.7 mm). There was a difference between the surgeons in terms of resection margin with operators 1,2 and 3 having 7.8 mm, 4.15 mm and 5.1 mm median resection margin respectively (p = 0.054). Conclusions: This navigation approach could represent a useful tool for intra-operative guidance in non-anatomical resection alongside conventional ultrasound guidance. A clinical pilot trial with 10 patients is currently in planning and will start beginning of 2020.

Recurrence at surgical margin following hepatectomy for colorectal liver metastases is not associated with R1 resection and does not impact survival

BackgroundResection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival. MethodsClinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined. ResultsDuring the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001). ConclusionThe incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases.

Soft tissue reconstruction after pelvic amputation: The efficacy and reliability of free fillet flap reconstruction

The majority of hindquarter amputation defects can be reconstructed with local anterior or posterior thigh flaps. Less than 5% of soft tissue defects require free flap reconstruction after tumour resection. Lower extremity fillet flap is described for reconstructing such defects, but the majority of publications are case reports or short single institutional series. There is a lack of data regarding the oncological outcomes of this highly selected patient group. Three tertiary sarcoma units treated twelve patients with hindquarter amputation or hip disarticulation for oncological indications with a free flap reconstruction of the soft tissue defect. The median age of patients was 60 (range 12-76) years. Bone resection was carried out through the SI-joint in six patients and through the sacrum in five patients, with one patient undergoing hip disarticulation. Nine patients had R0 resection margin and three had R1 resection. The median surgical time and flap ischaemia time was 420 (249-650) and 89 (64-210)min, respectively. Median hospital and ICU stay was 18 (10-42) and 3 (1-8) days, respectively. Median blood loss was 2400 (950-10000)ml. There were three returns to theatre due to vascular compromise, with one total flap loss due to arterial thrombosis. Overall survival was 58% (95%CI 28-91%) both at 1-year and at 3-years. Carefully selected patients requiring hindquarter amputation with extensive soft tissue defect necessitating free flap reconstruction can be reconstructed with a lower extremity free fillet flap with low rate of local wound complications. Survival of these patients is similar to that in patients requiring less extensive resection.

Transanal endoscopic microsurgery with alternative neoadjuvant imatinib for localized rectalgastrointestinal stromal tumor: a single center experience with long-term surveillance.

Transanal endoscopic microsurgery (TEM) is widely used in the treatment of local rectal lesions and helps avoid radical surgery. This study evaluated the management and outcome in a long-term followed cohort of patients with localized rectal GIST underwent TEM with alternative neodajuvant imatinib (nIM). A retrospective cohort study was undertaken of patients identified from a case database at Department of General Surgery, Peking Union Medical College Hospital (PUMCH) over a continuous period, from January 2006 to December 2017. Over 12years, 42 patients presented with a primary rectal GIST in PUMCH. Median age was 49 (range 27-77) years. Neoadjuvant imatinib (nIM) therapy was used in 16 patients, significantly reducing mean tumor size from 4.41 to 2.46cm (p < 0.001) and mitotic index (p = 0.041). All of these patients underwent TEM with no tumor rupture, nIM therapy enabled sphincter-preserving surgery to be undertaken in 16 (16/42) patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumor clearance and all patients (42/42) achieve R0 resection and negative margin. Imatinib was also used as postoperative adjuvant treatment in 15 patients with high-risk GIST. Median follow-up was 77 (range 14-144) and overall survival is 100%. In 42 patients, Local recurrence (LR) occurred in 3 of 42 patients and 1 of 42 patients developed distant metastasis (DM) in 112months after TEM. In the univariate analysis, mitotic index (p = 0.028), NIH risk categories (p = 0.047) were predictive feature of local relapse. The application of nIM significantly decreased tumor size in large localized rectal GIST, which permitted TEM to preserve sphincter. The TEM procedure with alternative neoadjuvant imatinib therapy is a practicable treatment for patients with rectal GIST to preserve anus and have satisfied anal function.

Microscopic resection margins adversely influence survival rates after surgery for colorectal liver metastases: An open ambidirectional Cohort Study.

Liver resection is the most effective treatment for patients with colorectal liver metastases (CRLMs). Patients with tumour at the resection margin (R1) are reported to have worse survival compared to those with an uninvolved resection margin (R0). Recent data has questioned this finding. This study investigates whether R1 resections adversely influence survival when compared to R0 resections. Patients undergoing surgery for CRLM, identified from a prospectively maintained database, from January 2007 to January 2017, were included. Univariate and multivariate survival analyses were performed. p<0.05 was significant. 282 patients were included. Median age 72 (32-90) years. 236 patients (83.7%) had chemotherapy and surgery, whilst 46 (16.3%) had surgery alone. 149 patients (52.8%) were alive at the end of the study period. R1 resection on univariate survival analysis was associated with better survival (HR 2.12, 95%CI 1.60-4.61, p=0.0002). Multivariate analysis controlling for age and gender, identified presence of extrahepatic disease (HR 2.03, 95%CI 1.17-3.52, p<0.001), R0 resection (HR 0.33, 95%CI 0.19-0.59, p=0.003), primary tumour stage (HR 1.57, 95%CI 1.04-2.40, p=0.034) and primary tumour differentiation (HR 2.56, 95%CI 1.01-6.46, p=0.047), as prognostic factors for poorer survival. Five-year and 10-year survival were 54.3% and 41.7% respectively in patients with an R0 resection and, 25.8% and 17.2% in those with an R1 resection. The presence of extrahepatic disease, an R1 resection margin, advanced T-stage and poorer tumour differentiation were associated with worse survival in CRLM surgery and R0 resection is recommended.

Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study

BackgroundExtended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC.MethodsPatients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed.ResultsThe study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5–19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion.ConclusionThe median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

Chemotherapy Versus Chemotherapy Plus Chemoradiation as Preoperative Therapy for Resectable Gastric Adenocarcinoma: A Propensity Score-Matched Analysis of a Large, Single-Institution Experience.

We compared oncologic outcomes of patients who received neoadjuvant chemotherapy (CT) with those of patients who received neoadjuvant chemotherapy plus chemoradiation (CRT) for resectable gastric adenocarcinoma. We compared oncologic and survival outcomes of patients who received CT or CRT for gastric adenocarcinoma at our institution between July 1995 and July 2018. We analyzed propensity score-matched cohorts based on age, sex, race, tumor histologic characteristics, and clinical stage. We identified 440 patients (mean age 61 ± 12years, 62% male, 55% white); 345 (78%) received CRT, and 95 (22%) received CT. The propensity score-matched cohorts included 65 patients who received CT and 65 who received CRT. The CRT group had similar frequencies of R1 resection margins to the CT group (7.7% vs. 6.2%, p = 0.75) but significantly higher frequency of pathologic complete response (27.7% vs. 1.5%, p < 0.001). The CRT group had lower pathologic stages (p = 0.002). Median disease-free survival was 50.9months (95% confidence interval [CI]: 4.7-97.2) in the CT group and 122.1months (95% CI: 69.0-175.1) in the CRT group (p = 0.07). Median overall survival was 70.7months (95% CI: 23.9-117.5) in the CT group and 122.1months (95% CI: 68.7-175.4) in the CRT group (p = 0.21). Compared with CT, CRT for resectable gastric adenocarcinoma is associated with higher rates of pathologic complete response and subsequent lower final pathologic stage, but survival differences are not significant. Ongoing investigation is necessary to better determine the optimal neoadjuvant therapy and identify patients who receive optimal benefit from CRT. III.

Can the Falciform Ligament Be the Most Ergonomic Patch in Portal Vein Reconstruction?

The target in pancreatic cancer surgery is to achieve R0 resection margin. Portal vein resection and reconstruction may be required for a clear margin. This case series is an evaluation of pancreatic cancer patients who underwent portal vein resection during pancreatico-duodenectomy. From January 2012 to January 2020 pancreatico-duodenectomy was performed in 134 patients and all consecutively done surgeries have been included. Of these 9 subjects required portal vein resection (male = 6, female = 3). The mean age was 65 years. Primary suturing and repair of portal vein could be successfully done in 4/9, portal vein primary anastomosis achieved in 2/9, and in 3 of 9 patients the portal vein defect being larger was repaired and successfully closed using a patch prepared from the falciform ligament. The patch was sutured to the portal vein with a continuous 5/0 prolene stitch. None of the 3 patients with falciform patch had complications such as bleeding or stenosis after 5 months following surgery. This technique has been used so far in the repair of perforation of the stomach and duodenum, in the control of pancreatic fistula and most importantly in the repair of defects in the vena cava. This study suggests that locally and immediately available falciform ligament can be used as an autologous graft to patch portal vein defects and is a valuable technique.

A meta-analysis on surgery with or without postoperative radiotherapy to treat squamous cell esophageal carcinoma.

Esophageal cancer (EC) is the sixth most common cause of cancer-related mortality in the world. Currently, surgery is the recommended treatment modality when possible. The outcomes of surgery alone are poor, and postoperative radiotherapy (PORT) has been used to patients with esophageal squamous cell carcinoma (ESCC) for years. However, the value of PORT for patients with ESCC after curative resection remains controversial. To assess the benefits and harms of postoperative radiotherapy compared with surgery alone for patients with ESCC we performed in this meta-analysis. A comprehensive electronic literature search was performed via the Cochrane Library, MEDLINE and EMBASE from January 1st, 1990 to October 1st, 2018 for relevant trials. The primary outcomes of interest are overall survival (OS) and disease-free survival (DFS). A meta-analysis was performed to calculate the hazard ratio (HR) with 95% confidence interval (CI). Three randomized controlled trials (RCTs) and seven retrospective studies (RS) were included, for a total of 5640 patients with 1774 in the PORT group and 3866 in the surgery alone group respectively. Meta-analysis showed there were significant increases both for OS (HR 0.86, 95%CI 0.79-0.93, p=0.0004) and DFS (HR 0.74, 95%CI 0.63-0.87, p=0.004) for patients administered PORT compared with surgery alone. Regarding the postoperative recurrence, PORT can significantly reduce the local recurrence rate (OR 0.34, 95%CI 0.29-0.40, p<0.00001), while it showed no difference in distant metastasis (OR 1.09, 95%CI 0.91-1.30, p=0.37). Subgroup analysis demonstrated PORT can improve the OS for patients with positive lymph node (N+, HR 0.73, 95%CI 0.59-0.90, p<0.00001), curative resection (R0 resection, HR 0.81, 95%CI 0.73-0.90, p<0.0001) and T3 stage (HR 0.84, 95%CI 0.80-1.0, p=0.05). PORT improved the OS and DFS for patients with ESCC compared with surgery alone, and significantly reduced the local recurrence. PORT showed survival benefits for specific subgroups such as patients with positive lymph node, R0 resection margin and T3 stage.

Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis.

Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002). A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.

Outcome quality standards for surgery of colorectal liver metastasis.

Liver metastases are the most common malignant solid liver lesions, approximately 40% of which stem from colorectal tumors. Liver resection is currently the only curative treatment for colorectal cancer liver metastases (CRLM). However, there is a lack of consensus criteria to assess the results of this treatment. In order to evaluate the quality of surgical outcomes, it is necessary to identify quality indicators (QIs) and their corresponding quality standards (QS). We propose a simple method to determine QI and QS in CRLM surgery (CRLMS) and establish acceptable quality limits (AQL) for each QI. A systematic review of CRLMS results published from 2006 to 2016. Clinical guidelines, consensus conferences, and publications related to the CRLMS were reviewed to identify and select QIs. Once selected, a new review of the papers including the results of at least one of the QIs was performed. Statistical process control (SPC) method was applied to calculate the QS and AQL of each QI. The limits of variability were established from mean and confidence intervals at 95% and 99.8%. The most relevant QIs and its AQLs were postoperative mortality (2%, < 4.5%), overall postoperative morbidity (33%, < 41%), liver failure (5%, < 8%), postoperative hemorrhage (1%, < 3%), biliary fistula (6%, < 10%), reoperation (3%, < 6%), R1 resection margins (18%, < 25%), and overall survival at 12 and 60months (84%, > 77%; and 34%, > 25%, respectively). Despite its limitations, the present study constitutes the most extensive scientific evidence to date on QI and AQL in CRLMS and may constitute a reference in future studies.

Surgical management of recurrent colon cancer.

There have been significant developments in the management of advanced and recurrent colorectal cancer in recent decades. 70% of primary colorectal tumours arise in the colon and for patients with stage I-III disease, the standard of care is surgical resection followed by adjuvant therapy where appropriate. Locoregional recurrence (LR) occurs in 4-11.5% of patients following treatment of primary colon cancer with curative intent, and can be categorised as peri-anastomotic, mesenteric/paracolic (nodal), retroperitoneal and peritoneal. Of these, peritoneal recurrence is usually recognised as the most challenging type of recurrence to manage. Patients with isolated peri-anastomotic or limited nodal recurrence in the mesentery or retroperitoneum may be curable by radical salvage surgery, which often requires en bloc multi-visceral resection, while patients with low volume peritoneal metastases may be candidates for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ensuring complete resection along embryonic mesocolic planes or en bloc resection of contiguously involved structures are best strategies to reduce the likelihood of local recurrence through a R1 resection margin. The role of complete mesocolic excision (CME) with high vascular ligation has been demonstrated to increase nodal yield and improve overall survival although this is more contentious. In patients with T4a disease and serosal surface involvement, peritoneal recurrence represents the greatest threat. Efforts for early diagnosis of peritoneal recurrence in these patients or prophylactic treatment, while intuitive have not demonstrated the survival benefit that would be expected. Other than locoregional recurrence (LR), systemic recurrence may occur in up to 50% of patients who have undergone curative resection for colorectal cancer. In keeping with portal venous outflow, the most common site of systemic recurrence is the liver. Although previously thought to be a fatal condition, liver resection is now the standard of care where liver metastases can be completely resected with clear margins plus leaving an adequate liver remnant with intact vascular inflow, outflow and biliary drainage. This can usually be achieved in 26-45% of patients presenting with liver metastases. Liver surgeons at the forefront of liver resection have also developed techniques to induce liver hypertrophy so as to improve likelihood of resectability. Even where patients have non-resectable disease, ablative techniques have become increasingly common. Naturally, none of these would be possible without the advent of improved chemotherapeutic and biological options in the field of medical oncology. Pulmonary metastasectomy with curative intent may be possible in a small number (10%) of patients with lung metastases, which is associated with an overall survival of up to 40%. Unlike liver metastases, proportionally less patients with pulmonary metastases will be resectable. For these patients, several ablative options are available. For all patients with recurrent colon cancer, patient selection for radical salvage surgery and decisions surrounding treatment strategy (including use of systemic therapy or ablative procedures) should take place in a multidisciplinary team setting.

Tu1506 OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR DUODENAL LESIONS, A UNITED STATES EXPERIENCE

ntroduction: ESD for duodenal lesions is considered a high-risk procedure; however it is still beneficial for large duodenal adenoma, particularly when suspicious of high grade dysplasia (HGD). Although ESD for duodenal lesions is fairly described in Eastern literature, there are no publications regarding the outcome of duodenal ESD in the West. Discuss the outcome of US experience in performing duodenal ESD with a focus on the risks and precautions taken to achieve a successful procedure. This is a retrospective study of all patients who underwent duodenal ESD in two US tertiary centers. All procedures were performed by two endoscopists with prior expertise in ESD. Patients’ demographics and procedure outcomes were collected. Categorical data were presented as percentage and continuous data were presented as mean and SD or median with ranges. 23 patients were included (12F/11M), mean age was 63+ 8.9, mean lesions’ surface area of the resected specimen was 5.46+3.9 cm with a median length of 2.5 cm (Range:0.5-4.9 cm). Tubular adenomatous with low grade dysplasia was the most common finding on pathology (table 1). Mean procedure time was 105+30 minutes. En bloc resection was achieved in 69% of patients and R0 resection (margin free of dysplasia) was achieved in 73% of patients. ESD was converted to hybrid ESD/snare resection as salvage therapy due to complications or technical difficulties in 10 out of 23 patients. Adverse events during procedures were seen in 5 patients, 4 with microperforations ( Figure 1) and one with bleeding (Table 2), all were managed endoscopically. Post procedural abdominal pain was noted in 4 patients (two of the four patients were discharged home after the procedure and were readmitted for pain next day) and one patient developed a retroperitoneal abscess, presented initially with abdominal pain after the procedure. All patients were treated with intravenous fluid and antibiotics. None of the patients required surgical intervention but three out of the five patients required more than 3 days of hospital stay. Lesion recurrence was seen in 2 patients (8.6%), both patients had an R1 resection (margin were involved with dysplasia). None of the patients with R0 resection had recurrence (0/17). Although duodenal ESD is feasible, it is associated with a higher rate of post procedural events, mainly abdominal pain requiring admission. Based on our data, we recommend post procedural observation for 24 hours with conservative treatment with IV fluid and antibiotics to minimize the risk of post procedural abdominal pain.Figure 1Microperforation during duodenal ESDView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Real-world survival outcomes of using neoadjuvant chemotherapy in pancreatic cancer patients: Findings from the PURPLE clinical registry.

e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p &lt; 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p &lt; 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p &lt; 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p &lt; 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.

Outcomes of Patients with Clinical Stage I-IIIA Large-Cell Neuroendocrine Lung Cancer Treated with Resection.

Large-cell neuroendocrine carcinoma (LCNEC) is a rare malignancy with poor prognosis. The rationale of the study was to determine the survival of LCNEC patients in I–IIIA clinical stages who underwent resection. A total of 53 LCNEC (89%) and combined LCNEC (11%) patients in stages I–IIIA who underwent surgery with radical intent between 2002–2018 were included in the current study. Overall survival (OS) and time to recurrence (TTR) were estimated. Uni- and multivariable analyses were conducted using Cox-regression model. Patients were treated with surgery alone (51%), surgery with radiochemotherapy (4%), with radiotherapy (2%), with adjuvant chemotherapy (41%), or with neoadjuvant chemotherapy (2%). The median (95% Confidence Interval (CI)) OS and TTR was 52 months (20.1–102.1 months) and 20 months (7.0–75.6 months), respectively. Patients treated in clinical stage I showed better OS than patients in stages II–IIIA (p = 0.008). Patients with R0 resection margin (negative margin, no tumor at the margin) and without lymph node metastasis had significantly better TTR. In the multivariate analysis, age was an independent factor influencing OS. Recurrence within 1 year was noted in more than half cases of LCNEC. R0 resection margin and N0 status (no lymph node metastasis) were factors improving TTR. Age >64 years was observed as a main independent factor influencing OS.