Higher R0 Resection Rate Research Articles

Impact of the distance from the root of the splenic artery to the tumor in patents with the pancreatic body/tail cancer.

221 Background: The impact of the distance from the root of the splenic artery to the tumor (DST) on prognosis and selection of operative procedures in patients with pancreatic body/tail cancer remains to be unclear. Methods: Between 2008 and 2018, 98 and 17 patients who underwent distal pancreatectomy (DP) and DP with celiac axis resection (DP-CAR) for conventional pancreatic ductal carcinoma were retrospectively analyzed. DST (mm) was measured by preoperative CT scan images. The indications for DP-CAR are the following: tumor involvement of the common hepatic artery and/or the celiac artery or difficulty in keeping surgical margin at the stump of the splenic artery. Results: Patients with DST = 0 had longer operation time ( p = 0.005), greater amount of blood loss ( p= 0.002), and higher morbidity rate ( p= 0.010) than those with DST > 0. The rate of introducing adjuvant chemotherapy in the DST = 0 group was significantly lower than that in the DST > 0 group (50% vs. 82%, p= 0.012). The median survival time (MST) of the DST = 0 group was significantly worse than that of the DST > 0 group (20 vs. 56 months, p< 0.001). In contrast, there was no significant difference of MST between the groups of 0 < DST≤10 and DST > 10 ( p= 0.499). Multivariate analyses revealed that DST = 0 (HR 4.51, p= 0.001), preoperative CA19-9 ≥40 U/mL (HR 2.91, p= 0.032) and preoperative neutrophil-to-lymphocyte ratio ≥2.3 (HR 2.49, p= 0.001) were independent prognostic factors. Regarding to the operative procedures, DP-CAR was performed 12 out of 14 patients with DST = 0, and 5 out of 16 patients with 0 < DST≤10. In the DST = 0 group, DP-CAR presented greater amount of dissected lymph nodes, higher rate of R0 resection, and lower rate of recurrence despite they were not identified statistically significant. In the 0 < DST≤10 group, DP-CAR tended to need longer operative time and higher rate of blood transfusion compared to DP, while there was no difference of prognosis. Conclusions: Multidisciplinary treatment including DP-CAR should be warranted for patients with DST = 0, which was a prognostic indicator. If surgical margin at the root of the splenic artery is secured in patients with DST > 0, DP should be an acceptable procedure.

Feasibility and safety of distal pancreatectomy with en bloc celiac axis resection (DP-CAR) combined with neoadjuvant therapy for borderline resectable and unresectable pancreatic body/tail cancer

Introduction: Pancreatic body/tail cancer commonly invades the hepatic artery or celiac artery, making surgical resection difficult. Distal pancreatectomy with celiac axis resection (DP-CAR) has recently been performed to achieve curative resection of these tumors. However, the safety and efficacy remain unclear. This study aimed to clarify the efficacy and safety of DP-CAR, mainly focusing on the combination with neoadjuvant therapy (NAT). Method: We retrospectively reviewed 31 consecutive patients with pancreatic ductal adenocarcinoma who underwent DP-CAR between 2010 and 2016. Data from 7 patients who underwent DP-CAR without NAT were used as reference (upfront surgery: US). Result: Gemcitabine + S-1 (GS) (n=17) and gemcitabine + albumin-bound paclitaxel (GnP) (n=8) were frequently used as NAT. DP-CAR following NAT was performed safely with 1 death, resulting in a mortality rate of 3%. The median survival time (MST) in the NAT group was 38.6 months, while that in the US group was 15.6 months. The NAT group had a high R0 resection rate (74%), while only 1 of 7 cases in the US group achieved R0 resection. Within the NAT group, patients treated with GS showed favorable overall survival with 39.5 months of MST, while that of patients treated with GnP was 19.8 months. Conclusion: The combination of NAT and DP-CAR was feasible and safe for pancreatic body/tail cancer invading the celiac artery and/or hepatic artery. This strategy should be further assessed for the optimal regimen and duration of NAT in prospective studies.

How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort.

Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1months follow-up, overall survival (OS) and disease-free survival were 45.4months and 16.2months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5months; P = 0.007). Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

Progress in conversion therapy for originally unresectable gastric cancer

Conversion therapy is adopted to achieve radical cure for patients with originally unresectable but potentially resectable late stage gastric cancer, who obtain partial or complete remission after systemic chemotherapy, to acquire relatively longer postoperative survival and recurrence-free survival. Some of the previous researches on conversion therapy for originally unresectable gastric cancer suggest that high chemotherapy response rate, high pathological response rate and R0 resection rate are associated with favorable prognosis. And the efficacy of patients with lymphatic metastasis is better than that of those with peritoneal metastasis. The protocol of conversional chemotherapy varies and so does its efficacy according to different reports. Latest clinical researches indicate that initially unresectable gastric cancer gained higher remission rate and better chance of R0 operation and consequently prolonged survival from paclitaxel based triplet chemotherapy. However, not all originally unresectable gastric cancer can benefit from conversion therapy due to the high heterogeneity of its biological behavior. Regarding the enormous number of originally unresectable gastric cancer patients, it will be a research hot spot in the field of surgical oncology, on screening criteria to select cases suitable for conversion. Exploration on conversion therapy for gastric cancer is still at initial stage, and reports that have been published are mostly single-centered with limited sample, lacking of sufficient evidence on its feasibility, safety and efficacy. Expert consensus on conversion indication, case selection, chemotherapy regimen, efficacy assessment and resection range is absent. So it is in urgent need for higher level clinical evidence to support and guide this practice. Such goal can never be achieved without joint efforts of all parties to carry out clinical trial to modify the practice of conversion therapy for late stage gastric cancer, and determine the proper selection of suitable candidates for conversion therapy, eventually to offer optimal strategy for originally unresectable gastric cancer patients. Thus, this article focuses on reviewing research progress of conversion therapy for originally unresectable late stage gastric cancer.

SBRT with Simultaneous Integrated Boost Results in High Rate of R0 Resection in Borderline Resectable Pancreatic Adenocarcinoma

Surgical resection for pancreatic adenocarcinoma offers a significantly improved prognosis with a distinct advantage of potentially curative (R0) versus palliative (R1/R2) surgery. Stereotactic body radiation therapy (SBRT) has emerged as a treatment option that has potential to pull the tumor off adjacent vascular structures and therefore improve surgical outcomes. We reviewed our rates of complete (R0) resection following neoadjuvant chemotherapy and SBRT for borderline resectable patients with pancreatic adenocarcinoma. Retrospective review of patients treated with SBRT to the pancreas between October 2015 and November 2017. A total of 26 patients were treated with SBRT to pancreas. All patients were treated with 5 fraction SBRT after fiducial marker placement and 4D treatment planning. Mean dose is 3250 cGy. Eight of the 26 patients received simultaneous integrated boost (SIB) to tumor vessel interface. Mean SIB dose 4150 cGy. Twelve medically operable patients received neoadjuvant chemotherapy; 7 FOLFIRINOX, 4 gemcitabine/abraxane, and one gemcitabine/pemetrexed. Of the 12 medically operable patients, 9 were classified as borderline resectable, and 3 were classified as unresectable based on NCCN criteria. Eight of 9 borderline resectable patients underwent successful pancreatoduodenectomy with R0 resection (89%). No severe toxicity was observed. SBRT provides a promising way to treat locally advanced and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage and improve the likelihood of R0 resection. Further exploration of SIB may be warranted in borderline resectable disease.

GR01.03 Surgical Oncology

In this section we will address the controversial areas of surgical management in the more advanced stages of thymoma. Using case-based discussion we will debate the following clinical scenarios: Stage III Thymic tumours ( with invasion of great vessels) Is there a role for primary surgical debulking leaving an intentional R2 resection? There is little survival evidence to support intentional debulking but such procedures may reduce the dose and extent of radiotherapy subsequently required and therefore the associated morbidity [1]. However, there is a lack of supportive evidence for debulking surgery in thymic carcinoma. [2,3] Should primary treatment be chemoradiotherapy followed by consolidation surgery? Induction therapy is feasible in locally advanced thymic tumours and has been reported to achieve around a 50% partial response. A complete pathological response has not been seen but such treatment can facilitate a high rate (over75%) of R0 resection.[4] Stage IVa Thymic tumours – pleural/pericardial deposits Is there a role for radical surgery? The International Thymic Malignancies Interest Group have recommended that in locally-advanced Stage IVa patients with pleural involvement, major pleural resections, including pleurectomy/decortication or extrapleural pneumonectomy are indicated, provided a complete resection of the pleural deposits is anticipated, usually in a multidisciplinary setting [5] Should this be extrapleural pneumonectomy or thymectomy and extended pleurectomy/decortication? As in other disease, extrapleural pneumonectomy (EPP) is associated with a high 30 day mortality of up to 17% (6). Providing a complete resection can be achieved there is no difference between EPP and extended pleurectomy decortication (EPD) (7] and median survival may exceed 4 years. The contribution of occult nodal metastases must be recognized and radical resection must include lymph node dissection. Stage migration due to lymph node metastases, WHO-classification type C, and T3/4-status are associated with inferior survival but extended surgery has been found to be the only independent significant prognosticator in multivariate analysis [8,9]. Which surgical incision is best? Radical resections can be facilitated by extended approaches which are well tolerated and adequate exposure is necessary to ensure a complete resection Recurrent thymic tumour – after previous resection Is there evidence that extending local control prolongs overall survival over systemic therapy alone? Survival is acceptable and superior to non surgical treatment if complete resection of recurrence is achieved. There is no evidence to support debulking of recurrent thymoma [10] A significant poorer prognosis is associated with multiple versus single relapses, Masaoka stage III primary tumour versus Masaoka stage I-II primary tumour, distant versus loco-regional relapses and B3 histotype versus other. On multivariate analysis, completeness of resection, number of metastases, Masaoka stage of primary tumour and site of relapse were identified as the only independent predictors of prognosis [10] The relative rarity of thymic neoplasms has contributed to the lack of high grade evidence from randomized controlled trials of large numbers of patients. Most supportive evidence for radical surgery in advanced thymic malignancies has therefore been provided by relatively small selected case series. However, the formation of larger collaborative groups with cumulative databases has provided more robust support for extended surgical procedures that many have avoided previously. The superiority of resection as part of multimodality treatment over non-surgical treatment alone seems to be justified provided high quality surgical standards are maintained.

Short-term efficacy and safety of the synchronous neoadjuvant chemoradiotherapy with paclitaxel plus carboplatin in stage III adenocarcinoma of esophagogastric junction

To evaluate the short-term efficacy and safety of neoadjuvant synchronous chemoradiotherapy (paclitaxel plus carboplatin regimen) in stage III adenocarcinoma of esophagogastric junction (AEG). Forty cases clinically diagnosed as stage III AEG were prospectively enrolled at the Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Hebei North University from December 2014 to November 2017 and then were randomly divided into paclitaxel plus carboplatin combined with synchronous radiotherapy group(neoadjuvant group) and direct operation group. Inclusion criteria was as follows:(1) AEG was diagnosed by gastroscopic biopsy and III stage was confirmed by ultrasound endoscopy and spiral CT;(2) physical strength score ≥70, and age ≤75 years old; (3) no contraindications of chemoradiotherapy and operation. Exclusion criteria was as follows:(1) patients voluntarily withdrew or refused the treatment;(2) occurrence of severe anaphylaxis; (3) uncontrollable events happened during treatment and treatment was unable to continue;(4) tumor developed obviously during treatment. Preoperative neoadjuvant synchronous chemoradiotherapy used TP regimen: paclitaxel 80 mg/m², drug concentration-time area under curve of carboplatin= 1.5 mg×ml⁻¹×min⁻¹, once per week for 9 weeks; radiotherapy began at the second week, 40 Gy/20 F, completed within 4 weeks. Operative procedure of both groups was radical resection of cardiac cancer(D2). Postoperative chemotherapy regimen was oral Tegafur(Gimeracil and Oteracil potassium). The side effects, diet situation, change of gastroscopic image after treatment in patients of neoadjuvant group were observed and efficacy evaluation of chemotherapy was performed according to solid tumor efficacy evaluation criteria of US National Cancer Institute. Operation-associated parameters, including R0 resection rate, lymph node metastasis, operative mortality and postoperative complications, were compared between two groups. There were no significant differences in baseline information between the two group (all P>0.05). One case in neoadjuvant group was excluded because of perforation at lesion site 7 weeks after chemotherapy. The side effects of 19 cases in neoadjuvant group were mainly alopecia (100%) and marrow inhibition (68.4%), while 3-4 degree side effects were alopecia(8/19,42.1%), leukopenia (3/19, 15.8%) and neutropenia(3/19, 15.8%). Complete remission was observed in 4 cases; partial remission was observed in 13 cases and stable disease in 2 cases, with an objective response rate of 89.5% and a disease control rate of 100%. Before neoadjuvant chemotherapy, 16 cases were difficult to take liquid diet and 3 cases received liquid diet only, while after 12 weeks of neoadjuvant chemotherapy, all the 19 cases received normal diet. Besides, after neoadjuvant chemotherapy, gastroscopic examination showed close healing of cardiac ulcer, disappearance of swelling, and renewal of normal mucosa. Compared to direct operation group, neoadjuvant group had less number of positive lymph node (4.9±3.6 vs. 8.8±2.8, P<0.05) and higher R0 resection rate (94.7% vs. 50.0%, P<0.05). Total number of harvested lymph node was not significantly different between two groups (19.1±2.5 vs. 18.6±7.0, t=0.326, P=0.746). There was no surgical death in either group. One case in direct operation group developed postoperative inflammatory obstruction. No associated complication was found in neoadjuvant group. Paclitaxel plus carboplatin combined with synchronous radiotherapy can elevate the R0 resection rate of patients with stage III esophagogastric junction adenocarcinoma, without increasing operative mortality and postoperative complications.

Benefits of the superior mesenteric artery first approach during open and laparoscopic pancreatoduodenectomy

Introduction: Initially proposed to assess resectability and improve surgical resection margin status of patients undergoing pancreatoduodenectomy for pancreatic head tumors, the superior mesenteric artery (SMA)-first approach may also improve surgical safety allowing better identification of pancreatoduodenal arteries originating from the SMA and easier preservation of aberrant/replaced right/common hepatic arteries (RHA/CHA) originating from the SMA. We describe our experience with SMA-first approach during Open and Laparoscopic pancreatoduodenectomy (OPD and LPD). Methods: We used the SMA-first approach in 63 consecutive patients (June 2015–June 2017), 44 undergoing OPD and 19 LPD. Demographic, clinical-pathological, and perioperative data were prospectively collected and retrospectively analyzed. Results: The SMA-first approach was feasible in all study patients and was useful in the management of RHA/CHA anomalies in 14% of patients. Overall, median intraoperative blood loss was 150 ml, with 16% of patients undergoing intraoperative blood transfusion. OPD patients had higher intraoperative median blood loss (200 ml) and more frequently needed intraoperative blood transfusion (23%), compared to LPD (100 ml and 0%,respectively, p< .05). OPD patients underwent more complex procedures with higher rates of vascular resection/reconstruction (55%) and total pancreatoduodenectomy (43%), compared to LPD (0% and 5%; p< .005 for both comparisons). Among 34 patients affected by pancreatic ductal adenocarcinoma, the rate of R0 resection was 85% overall and similar between LPD and OPD. Conclusion: SMA-first approach is feasible, safe and oncologically sound, allowing for low intraoperative blood loss and high rate of R0 resection, and may be of help when a vascular resection/reconstruction is needed or a LPD is attempted.

Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial

PurposeThe efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC.Patients and MethodsFrom June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m2 IV day 1, or 25 mg/m2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival.ResultsThe pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S (P = .212).ConclusionThis trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

Current status and controversies in the management of borderline resectable pancreatic cancer

The borderline resectable pancreatic cancer is high a controversial hotspot in the field of pancreatic surgery, and the controversy mainly focuses on definition and treatment. Five famous experts and their teams in pancreatic surgery discussed present situation and dilemmas in treatment of borderline resectable pancreatic cancer based on clinical experiences. Professor Hao Chunyi has reviewed and analyzed origin of the definition and treatment model of borderline resectable pancreatic cancer, and proposed that high-level pancreatic disease center and multidisciplinary collaboration diagnosis and treatment may be the best choice for resectable pancreatic cancer. Professor Liu Xubao suggested surgical treatment for most of borderline resectable pancreatic cancer, and whether or not tumor invades adjacent blood vessels and invasion level will be used to decide direct surgery or neoadjuvant therapy. Professor Sun Bei proposed 6 causes, and direct surgery may be more realistic and feasible option for borderline resectable pancreatic cancer. Professors Liang Tingbo and Bai Xueli recommended that neo-adjuvant therapy should be performed due to defeat hiding micrometastasis lesions and reduce tumor burden, and there was a higher R0 resection rate and lower lymph node metastasis rate after neoadjuvant therapy, meanwhile, it can also increase cure rate and is benefited to survival. Key words: Pancreatic neoplasms; Pancreatic cancer; Resectable; Borderline resectable; Direct surgery; Neoadjuvant therapy

Visceral infiltration of intrahepatic cholangiocarcinoma is most prognostic after curative resection - Retrospective cohort study of 102 consecutive liver resections from a single center

IntroductionIntrahepatic cholangiocarcinoma (ICC) is a rare malignancy, and therefore large unicenter series on the surgical outcome are rare in the literature, and prognostic factors for overall survival in the literature vary widely. MethodsAll patients who underwent surgery for ICC were prospectively recorded. The type of resection, operative details, histological results, morbidity, mortality, overall and recurrence-free survivals as well as prognostic factors were assessed. Prognostic factors were examined by univariate and multivariate analyses. P-values <0.05 were considered significant. ResultsBetween January 2008 and December 2015, 102 patients underwent a resection with curative intent and were included in this analysis. Major and extended hepatectomies were performed in 19 and 53 cases, respectively. Twenty-eight patients had additional vascular and 35 patients additional visceral resections. R0-resections were achieved in 87 patients (85.3%). Median recurrence-free and overall survivals were 9.3 and 20.8 months, respectively. N-stage, infiltration of surrounding structures and UICC stage were significant prognostic factors in the univariate analysis. Multivariate analysis depicted only visceral infiltration (p = 0.011) as independent predictor for overall survival, and tumor size (p < 0.001), N-stage (p = 0.007), R-stage (p = 0.008) and M-stage (p = 0.009) for recurrence-free survival. ConclusionAn aggressive surgical approach achieves a high rate of R0 resections even in advanced ICC. Visceral infiltration is an independent predictor for overall survival for ICC after curative resection.

Chemotherapy vs chemoradiation as preoperative therapy for resectable pancreatic ductal adenocarcinoma: a propensity score adjusted analysis

Background: Among patients with resectable pancreatic ductal adenocarcinoma (PDAC), the role of preoperative chemoradiation therapy (CRT) remains controversial. Methods: All patients with anatomically resectable PDAC who received preoperative chemotherapy alone (n = 31, 12%) or CRT alone (n = 227, 88%) prior to pancreatectomy between 1999 and 2014 were included. Propensity score matching with inverse probability weighting was conducted based on age at diagnosis, baseline CA 19-9, and procedure type. Results: After propensity score weighting, patients who received preoperative CRT alone were more likely to undergo a margin negative (91% vs 79%, p < 0.01) and node negative (53% vs 23%, p < 0.01) resection than patients who received chemotherapy alone. With a median follow-up time of 3.7 years, patients who received preoperative CRT had a lower rate of locoregional recurrence (LR; 16% vs 33%, p < 0.01) but had similar median overall survival (OS; 2.8 vs 2.2 years, p = 0.09) when compared with those received chemotherapy alone. On multivariate analysis, only baseline CA 19-9 (HR 1.2, 95%CI 1.1–1.3) and positive lymph nodes (HR 1.5, 95%CI 1.0–2.2) were statistically significantly associated with OS, while larger tumor size (OR 1.5, 95%CI 1.3–1.8), positive lymph nodes (OR 3.1, 95% CI 1.8–5.6), and preoperative chemotherapy (OR 1.8, 95%CI 1.1–2.9) were significantly associated with an increased risk of LR. Conclusion: Preoperative CRT alone was associated with a higher R0 resection rate, a lower rate of positive lymph nodes, a reduced incidence of LR, and a similar OS compared to preoperative chemotherapy alone. These findings, although limited by their retrospective nature, provide support for the continued use of radiation therapy in the preoperative management of PDAC and its incorporation into future clinical trial protocols.

Technique of “mini-invasive radical antegrade modular pancreatosplenectomy” for pancreatic cancer

Pancreatic cancer spreads preferentially into the retroportal lamina that is frequently invaded at the celiac trunk (CT) and/or superior mesenteric artery (SMA) margins. In 2007, for the first time, it has been proposed by the team of Prof. Strasberg SM an innovative surgical technique for open surgery called radical antegrade modular pancreatosplenectomy (RAMPS) which allows to increase the circumferential resection margins in case of pancreatic cancer of the body of the pancreas and it is associated to a high rate of R0 resection. Currently, it is possible to perform such intervention mini-invasively. The present manuscript reports our technique.

Improving Long-Term Outcomes for Patients with Extra-Abdominal Soft Tissue Sarcoma Regionalization to High-Volume Centers, Improved Compliance with Guidelines or Both?

Introduction Optimization of outcomes of extra-abdominal STS is not clearly understood. We sought to determine whether hospital surgical volume and adherence to NCCN guidelines, or both, are associated with outcomes in the treatment of extra-abdominal soft tissue sarcoma (STS). Methods The National Cancer Database (NCDB) was queried for patients undergoing surgery for extra-abdominal STS diagnosed from 2003 to 2007. Mean annual hospital volume for STS surgery was divided into volume terciles (1T ≤3, 2T 4–10, and 3T ≥11 cases/year). Adherence to NCCN guidelines was determined. Primary outcome was overall survival. Results Our study population consisted of 13,684 patients with a median age of 56 years. 3T hospitals were more likely to adhere to NCCN guidelines for stage III patients (63% versus 47%; p ≤ 0.001) than 1T hospitals. On multivariable analysis, adherence to NCCN guidelines was associated with improved survival (HR = 0.79, CI 0.73–0.87; p < 0.001), but hospital volume was not (3T versus 1T: HR = 0.92, CI 0.82–1.02; p=0.12). Five-year overall survival was comparable for compliant groups at 1T, 2T, and 3T hospitals (72%, 72.4%, and 72.6%, resp.). 3T hospitals were not associated with a lower risk of 30-day mortality (OR 0.70, 95% CI 0.44–1.11) compared to 1T hospitals but did have a higher R0 resection rate (OR 1.43, 95% CI 1.32–1.54). Conclusions Adherence to NCCN guidelines, irrespective of hospital volume, is associated with improved overall survival for patients with extra-abdominal STS. High-volume hospitals more often adhere to guidelines, but low-volume hospitals that follow national guidelines may achieve comparable outcomes.

Associating liver partition and portal vein ligation for staged hepatectomy versus conventional two-stage hepatectomy: a systematic review and meta-analysis

BackgroundIt is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma. Conventional two-stage hepatectomy (TSH) is commonly considered to accelerate future liver regeneration despite its low regeneration rate. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which is characterized by a rapid regeneration, has brought new opportunities.MethodsRelevant studies were identified by searching the selected databases up to September 2017. Then, a meta-analysis of regeneration efficiency, complication rate, R0 resection ratio, and short-term outcomes was performed.ResultsTen studies, comprising 719 patients, were included. The overall analysis showed that ALPPS was associated with a larger hyperplastic volume and a shorter time interval (P < 0.00001) than TSH. ALPPS also exhibited a higher completion rate for second-stage operations (odds ratio, OR 9.50; P < 0.0001) and a slightly higher rate of R0 resection (OR 1.90; P = 0.11). Interestingly, there was no significant difference in 90-day mortality between the two treatments (OR 1.44; P = 0.35).ConclusionsThese results indicate that compared with TSH, ALPPS possesses a stronger regenerative ability and better facilitates second-stage operations. However, the safety, patient outcomes, and patient selection for ALPPS require further study.

Results of a prospective phase 2 clinical trial of induction gemcitabine/capecitabine followed by stereotactic ablative radiation therapy in borderline resectable or locally advanced pancreatic adenocarcinoma

PurposeStereotactic ablative radiation therapy’s (SABR’s) great conformity and short duration has become an attractive treatment modality. We report a phase 2 clinical trial to evaluate efficacy and safety of induction chemotherapy (ICT) followed by SABR in patient with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Methods and materialsPatients with biopsy-proven BR or LA PDAC were treated with four 21-day cycles of intravenous gemcitabine and oral capecitabine. Patients were restaged within 4 weeks after ICT by computed tomography and treated by 3-fraction SABR if no metastasis or progressive disease was identified. Patients were restaged 4 weeks following SABR to determine resectability. Tumor response was assessed with carbohydrate antigen 19-9. ResultsThirty-five patients (19 BR/16 LA) were enrolled. The median age was 71.8 years (range, 50.6-81.1). ICT was completed in 91.4% (n = 32) of patients. All patients who completed ICT completed SABR. Of those 32 patients, 34.3% (n = 12: 10 BR, 2 LA) underwent pancreaticoduodenectomy and 11 of 12 (91.7%) received R0 resection. Median overall survival was 18.8, 28.3, and 14.3 months for the entire cohort, BR, and LA, respectively. The 2-year local progression-free survival (LPFS) was 44.9%, 40%, and 52% for the entire cohort, BR, and LA, respectively. For BR patients, multivariate analysis showed surgery was associated with better overall survival and LPFS. One-year LPFS for patients with surgery was 80% and 44% without surgery. Within the 15.4-month follow-up, no grade 3+ toxicity from SABR was observed. No significant quality of life change was observed before and after ICT, SABR, or surgery for BR or LA patients. ConclusionsThis is the first prospective phase 2 study to investigate the feasibility and efficacy of a 12-week gemcitabine/capecitabine ICT followed by SABR for BR or LA PDAC. The results suggest excellent tolerability, high R0 resection rates, and acceptable posttreatment complications.

Esophageal endoscopic submucosal dissection using sodium hyaluronate is safe and effective

Background/Aims: A submucosal cushion of sodium hyaluronate facilitates gastric and colorectal endoscopic submucosal dissection (ESD). However, few studies have evaluated the utility of sodium hyaluronate for ESD of esophageal lesions. The aim of this study is to evaluate the utility and safety of sodium hyaluronate for ESD of superficial esophageal squamous cell neoplasms (ESCN).Material and methods: We retrospectively reviewed 111 ESCN in 86 patients treated by ESD between September 2007 and April 2013. There were four double cancers, with 107 ESD procedures analyzed.Results: The en bloc resection rate was 99% (106/107). The R0 resection rate was 93% (99/107). Of 106 specimens resected en bloc, four specimens had a positive horizontal margin, two specimens had non-assessable horizontal margins and one specimen had non-assessable horizontal and vertical margins. One patient with a non-assessable horizontal margin developed local recurrence seven months later, treated by repeat ESD. Delayed bleeding occurred in two procedures (2%), and intra-procedural perforation occurred in four (4%). None required operative repair. Endoscopy trainees performed 33 of 107 (31%) ESD procedures. Post-ESD stenosis requiring dilation occurred following five procedures (5%).Conclusions: Sodium hyaluronate for ESD of ESCN achieves a high R0 resection rate with a low rate of adverse events.

Radical antegrade modular pancreatosplenectomy versus standard procedure in the treatment of left-sided pancreatic cancer: A systemic review and meta-analysis

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS), first reported by Strasberg in 2003, has attracted increasing attention in the treatment of left-sided pancreatic cancer. The limited number of cases eligible for RAMPS makes it difficult to perform any prospective randomized trial of RAMPS versus the standard procedure. Therefore, we performed this systemic review and meta-analysis of the current data to clarify the role of the RAMPS procedure.MethodsA literature search was performed in electronic databases, including PubMed, Medline, Embase, CNKI and the Cochrane Library. Studies comparing RAMPS with the standard procedure were included in this meta-analysis. R0 resection rate, recurrence rate at the end of the follow-up, overall survival (OS) and disease-free survival (DFS) were measured as primary outcomes. Revman 5.3 was used to perform the analysis.ResultsSix retrospective cohort studies with a total number of 378 patients were included in our analysis. Meta-analysis revealed that RAMPS was correlated with higher R0 resection rates [Odds Ratio (OR) 95% confidence interval (CI), 2.19 (1.16 ~ 4.13); P = 0.02] and successful harvest of more lymph nodes [weighted mean difference (WMD) 95% CI, 7.06 (4.52 ~ 9.60); P < 0.01] compared with the standard procedure. However, no statistically significant difference was found between the procedures with respect to recurrence rates [OR 95% CI, 0.66 (0.40 ~ 1.09); P = 0.10], OS [Hazard ratio (HR) 95% CI, 0.65 (0.42 ~ 1.00); P = 0.05] or DFS [HR 95% CI, 1.02 (0.62 ~ 1.68); P = 0.93].ConclusionsRAMPS is safe and oncologically superior to the standard procedure for the treatment of left-sided pancreatic cancer. However, high-grade evidence will be necessary to confirm the potential survival benefits of RAMPS.

Effectiveness of induction chemotherapy consisting of docetaxel, cisplatin, and S-1 (DCS) followed by esophagectomy for cT4 esophageal cancer

Introduction: The prognosis of cT4 esophageal cancer is dismal unless the tumor is completely removed by esophagectomy after induction treatment successfully reducing the tumor volume. However, esophagectomy for cT4 esophageal cancer after induction treatment is associated with high morbidity and mortality rates and recommended induction treatment remains unclear. The aim of the study is to evaluate the feasibility and efficacy of 3-course chemotherapy consisting of docetaxel, cisplatin, and S-1 (DCS) followed by esophagectomy in comparison with 2-course chemotherapy consisting of 5-FU, doxorubicin, and nedaplatin (FAN) for cT4 esophageal cancer in a prospective cohort study. Methods: Since 2002, we have performed a prospective cohort study of induction treatment in patients with cT4 esophageal cancer. FAN chemotherapy, 40-66 Gy chemoradiotherapy, and DCS chemotherapy was performed in patients with cT4 esophageal cancer during the period of 2002-2006, 2006-2013, and 2013-2016, respectively. The short- and long-term results of DCS group (n = 18) were compared with FAN group (n = 17). In DCS group’s patients, cStage III and IV diseases were found in 1 and 17 respectively, whereas the respective number was 3 and 14 in the FAN group’s patients. Results: The completion rate of the planned therapy was 89% and 65% in the DCS and FAN group, respectively (p = 0.121). The response rate for primary tumor (83%) of DCS group was significantly higher than that (35%) of FAN group (p = 0.006). However, the occurrence rate of the toxicity grade 3 or higher was not significantly different between two groups: 61% and 47% in the DCS and FAN group, respectively (p = 0.505). There were no treatment-related deaths during the chemotherapy in two groups. The esophagectomy rate was 67% of DCS group and 59% of FAN group, respectively (p = 0.733). R0 resection rate was 61% of DCS group and 47% of FAN group, respectively (p = 0.505). There were not significantly different between two groups but DCS group showed high Esophagectomy and R0 resection rates in comparison with FAN group. The surgery-related morbidity rate was 75% and 50% in DCS and FAN groups, respectively (p = 0.378). There were not significantly different between the 2 groups. The surgery-related mortality was occurred in two patients of FAN group, but there were not in DCS group. The 5-years overall survival rates for all patients, the 45% of DCS group was significantly better than 12% of FAN group (p = 0.029). Conclusion: The induction DCS therapy is safe and feasible, and has strong power to reduce tumor volume (response rate: 83%) even in cases of T4 esophageal tumor. Esophagectomy and R0 resection rates after the DCS therapy were better than those after the FAN therapy. Furthermore, the 5-years overall survival rates for all patients in DCS group significantly better than that in FAN group. Therefore, the DCS therapy may be promising as the induction treatment for cT4 esophageal cancer.

Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach

Background:Gastrointestinal stromal tumours (GISTs) with high-risk features have poor prognosis even if adjuvant treatment is given. Neoadjuvant imatinib may increase the cure rate by shrinking large GISTs and preserve organ function.Methods:We conducted an Asian multinational phase II study for patients with gastric GISTs ≥10 cm. Patients received neoadjuvant imatinib (400 mg/day) for 6–9 months. The primary end point was R0 resection rate.Results:A total of 56 patients were enroled in this study. In the full analysis set of 53 patients, neoadjuvant imatinib for ≥6 months was completed in 46 patients. Grade 3–4 neutropenia and rash occurred in 8% and 9%, respectively, but there were no treatment-related deaths. The response rate by RECIST was 62% (95% CI, 48–75%). The R0 resection rate was 91% (48/53) (95% CI, 79–97%). Preservation of at least half of the stomach was achieved in 42 of 48 patients with R0 resection. At the median follow-up time of 32 months, 2-year overall and progression-free survival rates were 98% and 89%, respectively.Conclusions:Neoadjuvant imatinib treatment for 6–9 months is a promising treatment for large gastric GISTs, allowing a high R0 resection rate with acceptable toxicity.