Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer

PurposeThe aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.MethodsSeventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0–1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.ResultsThe rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).ConclusionsNarrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

Prognostic factor analysis of irreversible electroporation for locally advanced pancreatic cancer – A multi-institutional clinical study in Asia

IntroductionIrreversible electroporation (IRE) is a modality that utilizes high electric voltage to cause cell apoptosis. IRE has been used to treat locally advanced pancreatic cancer (LAPC). However, studies of IRE via surgical approaches for LAPC are limited. This study aims to analyse the outcomes and related prognostic factors of IRE for Asian patients with LAPC.Materials and methodsFrom 2012 to 2017, this prospective trial for using IRE through surgical approaches for LAPC was conducted in 11 medical centres in Asia. All related and treatment outcomes were analysed from a prospective database.ResultsSeventy-four patients were enrolled. Thirty complications occurred in thirteen (17.6%) patients without mortality. The electrode placement direction (anteroposterior vs. craniocaudal, HR = 14.2, p < 0.01) and gastrointestinal invasion (HR = 15.7, p < 0.01) were significant factors for complications. The progression-free survival (PFS) rate in one year, three years, and five years were 69.1%, 48.7%, and 28.8%, and the overall survival (OS) rate in one year, three years, and five years were 97.2%, 53%, and 31.2%. In univariate analysis, the chemotherapy regimen, local tumour recurrence, axial tumour length, tumour volume, and serum carbohydrate antigen 19-9 levels were all significantly associated with PFS and OS. In multivariate analysis, the chemotherapy regimen was the only significant factor associated with PFS and OS. TS-1 (Tegafur, gimeracil, and oteracil) group has superior survival outcome than gemcitabine group.ConclusionThis study showed that combined induction chemotherapy and surgical IRE for LAPC is safe. For well-selected patients, IRE can achieve encouraging survival outcomes.     

Validation of the American Joint Committee on Cancer 8th edition staging system for the pancreatic ductal adenocarcinoma

Background & aimsThe American Joint Commission on Cancer (AJCC) 8th edition staging system for pancreatic ductal adenocarcinoma (PDA) contains several significant changes. This study aimed to validate the AJCC 8th edition staging system of PDA.MethodsWe analyzed patients with resected PDA between 2001 and 2017 using the Korean Pancreatic Cancer (K-PaC) registry. Overall survival (OS) was estimated using the Kaplan-Meier survival curves and compared via the log-rank test.ResultsIn total, 701 resected PDA patients were identified. During a median follow-up of 24.5 months, the median OS was 21.7 months. Meanwhile, the median OS of each stage according to the AJCC 8th edition was 73.5 months (stage IA), 41.9 months (stage IB), 24.2 months (stage IIA), 18.3 months (stage IIB), and 16.8 months (stage III). However, the new N-category (pN1 vs. pN2) did not subdivide prognosis, although the lymph node ratio (i.e., the ratio of the number of LN involved to the number of examined LN) did. Although pT3 and pN2 belong under stage III, pN2 has a significantly longer median OS than pT3 (16.9 months vs 11.2 months; p < 0.01).ConclusionThe AJCC 8th edition staging system appropriately stratifies the prognosis of PDA patients. However, the cutoff of the N-category is not statistically valid, and the new stage III includes a heterogeneous category (pN2 and pT4). Therefore, we propose that stage III be divided into stage IIIA (Tany N2 M0) and stage IIIB (T4 Nany M0).     

Laparoscopic distal pancreatectomy with regional lymphadenectomy through retroperitoneal-first laparoscopic approach (Retlap) for locally advanced pancreatic body cancer

BackgroundLaparoscopic distal pancreatectomy (LDP) is widely performed [1,2]. However, LDP with regional lymphadenectomy for locally advanced pancreatic cancer (LAPC) is technically demanding [3]. We previously reported a new strategy named “retroperitoneal-first laparoscopic approach (Retlap)” for distal pancreatectomy with en bloc celiac axis resection [4]. In this study, Retlap is applied during LDP with regional lymphadenectomy (see Fig. 1).MethodsThis video demonstrates the case of a 70-year-old woman with a 100 × 40-mm LAPC. Preoperative computed tomography revealed a large tumor near the root of the celiac axis and acute pancreatitis in the pancreatic head. An ample dorsal margin should be secured and regional lymphadenectomy performed because of the large tumor. In Retlap, the celiac axis was exposed using the retroperitoneal approach from the dorsal side of the pancreatic body, and then the left adrenal grand and left celiac ganglion were removed. Without interfering with the tumor, the root of the splenic artery was identified, facilitating easy performance of lymphadenectomy around the celiac axis and superior mesenteric artery in Retlap. After dividing the splenic artery, the procedure was converted to laparoscopic approach and resection was completed.ResultsThe operative time and estimated blood loss were 487 min and 45 mL, respectively. Pathological examination confirmed a negative surgical margin, and R0 resection was achieved with uneventful postoperative course.ConclusionRetlap was technically feasible and useful for achieving adequate and secure surgical margin and regional lymphadenectomy. Retlap can help secure the operative field of view in difficult cases of LAPC.     

Postoperative pancreatic fistulas decrease the survival of pancreatic cancer patients treated with surgery after neoadjuvant chemoradiotherapy: A retrospective analysis

Background and objectivesA postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT).MethodsPatients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF.ResultsDuring the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis.ConclusionsThe development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.     

Preoperative assessment and optimisation for pelvic exenteration in locally advanced and recurrent rectal cancer: A review

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints.     

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas – Matched-pair analysis with pancreatic ductal adenocarcinoma

IntroductionAdenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC).Materials and methodsAll patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC.ResultsOf 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP.ConclusionASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.     

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis

BackgroundThe incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated.MethodsOriginal studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3.ResultsNine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = −103ml [-135, −72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = −0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = −0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = −1.70 days [-2.34, −1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = −0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006).ConclusionsLTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.     

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

IntroductionPatients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices.Materials and methodsPatients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured.ResultsBefore treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression).ConclusionThese data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.     

Breast reconstruction after therapeutic or prophylactic mastectomy for breast cancer: A comparison of guideline recommendations

BackgroundThe purpose of this article is to illuminate differences in published clinical practice guideline recommendations for breast reconstruction after prophylactic and therapeutic mastectomy.MethodsTen guidelines were identified through a systematic search of websites and databases of reputable oncology guideline developers, and key differences and gaps in recommendations were noted. Quality assessment of the guidelines was conducted by three reviewers using the AGREE II tool, focusing on breast reconstruction specific documents rather than the general breast cancer guidelines.ResultsThe most comprehensive guidelines were published by Alberta Health Services, Cancer Care Ontario, the American Society of Plastic Surgeons, and the Association of Breast Surgery/British Association of Plastic Reconstructive and Aesthetic Surgeons. AGREE II scores in the domains of “Scope and Purpose” and “Clarity and Presentation” were ranked relatively high for all four guidelines while “Applicability” and “Editorial Independence” were ranked relatively low. The Alberta and Ontario guidelines were the overall highest ranked guidelines across all domains.ConclusionOverall, these guidelines provide consistent recommendations on who should receive breast reconstruction education, who is a candidate for postmastectomy breast reconstruction, and the appropriate timing of reconstruction and extent of mastectomy. Future updates from all should focus on expanding to include alloplastic and autologous forms of reconstruction and should include a broad scope of relevant questions.     

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis

ObjectivesThis study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.MethodsPubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients.ResultsTwenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38–2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23–0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06–0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11–9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45–0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55–0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent.ConclusionsThe current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.     

Paraaortic dissection in “total mesopancreas excision” and “mesopancreas-first resection” pancreaticoduodenectomies for pancreatic cancer: Useless,optional, or necessary?A systematic review

The mesopancreas does not have well-defined boundaries but is continuous and connected through its components with the paraaortic area. The mesopancreatic resection margin has been indicated as the primary site for R1 resection after PD in pancreatic head cancer and total mesopancreas excision has been proposed to achieve adequate retropancreatic margin clearance and to minimize the likelihood of R1 resection. However, the anatomy of the mesopancreas requires extended dissection of the paraaortic area to maximize posterior clearance. The artery-first surgical approach has been developed to increase local radicality at the mesopancreatic resection margin. During PD, the artery-first approach begins with dissection of the connective tissues around the SMA. However, the concept of the mesopancreas as a boundless structure that includes circumferential tissues around the SMA, SMV, and paraaortic tissue highlights the need to shift from artery-first PD to mesopancreas-first PD to reduce the risk of R1 resection. From this perspective the “artery-first” approach, which allows for the avoidance of R2 resection risk, should be integrated into the “mesopancreas-first” approach to improve the R0 resection rate.In total mesopancreas excision and mesopancreas-first pancreaticoduodenectomies, the inclusion of the paraaortic area and circumferential area around the SMA in the resection field is necessary to control the tumour spread along the mesopancreatic resection margin rather than to control or stage the spread in the nodal basin.     

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review

BackgroundChyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy.MethodsA systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality.ResultsLiterature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases.ConclusionsThe extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.     

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

BackgroundGallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC.Material and methodsFormalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed.ResultThe average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS.ConclusionTo achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.     

Implications for restaging in gastric cancer with peritoneal metastasis based on the 15th Japanese Classification of Gastric Carcinoma: An analysis from a comprehensive center

Backgroundand purpose: For gastric cancer patients with peritoneal metastasis (GCPM), there is no universally accepted prognostic staging system. This study aimed to validate the predictive ability of the 15th peritoneal metastasis staging system (P1abc) of the Japanese Classification of Gastric Carcinoma (JCGC).MethodsThe data of 309 GCPM patients from July 2007 to July 2017 were retrospectively analyzed. This study compared the prognosis prediction performances of P1abc, the previous JCGC PM staging (P123) and Gilly staging systems.ResultsThe survival curve revealed a significant difference in overall survival (OS) predicted by P1abc, P123 and Gilly staging (all P < 0.05), and the survival of the two adjacent substages were well distinguished by P1abc but not by P123 and Gilly staging. Both P123 and Gilly staging were substituted with P1abc staging in a 2-step multivariate analysis. The results showed that P1abc staging was superior to both P123 and Gilly staging in its discriminatory ability (C-index), predictive accuracy (AIC) and predictive homogeneity (likelihood ratio chi-square). A stratified analysis by different therapies indicated that for the P1a and P1b patients, OS following palliative resection combined with palliative chemotherapy (PRCPC) was better than that after palliative resection (PR) or palliative chemotherapy (PC) alone (P < 0.05). For the P1c patients, OS after receiving PC was significantly superior to that after receiving PRCPC or PR (P = 0.021).ConclusionP1abc staging is superior to P123 and Gilly staging in predicting the survival of GCPM patients. Surgeons can provide these patients with appropriate treatment options according to the corresponding substages within P1abc.     

The prognostic relevance of histologic subtype in appendiceal adenocarcinoma

BackgroundThe aim of this population-based study was to determine the prognostic value of the histologic subtypes mucinous (MAC), non-mucinous (AC) and signet ring cell (SRCC) adenocarcinoma among patients with appendiceal cancer.Methods and materialsData from the Netherlands Cancer Registry (NCR) of patients with primary appendiceal adenocarcinomas with MAC, AC and SRCC histologic subtype, diagnosed between 2001 and 2015 were used (n = 675). To categorize patients according to the recent histopathological classification, the NCR was linked with the Dutch Pathology Registry (PALGA). Log-rank tests and Kaplan-Meier analyses were performed to estimate overall survival (OS), and the cox proportional hazards model was run to identify prognostic factors.ResultsAC was the most frequently encountered histologic subtype (50.9%), followed by MAC (35.8%) and SRCC (13.3%). In locoregional disease, histologic subtype was not a prognostic factor for OS with 5-year survival rates for patients with AC, MAC and SRCC of 60.0%, 60.5% and 69.6% respectively (p = 0.68). Metastatic disease was more common in SRCC (53.8%) than in MAC (38.8%) and AC (23.4%) (p < 0.0001). Median OS for patients with metastatic disease was 12.6, 27.7 and 18.2 months in AC, MAC and SRCC respectively (p < 0.005). MAC was associated with higher survival compared to AC (HR 0.48, 95%CI 0.34–0.69). In subanalyses, MAC was only a positive prognostic factor compared to AC in patients with peritoneal metastases (HR 0.42, 95%CI 0.28–0.62).ConclusionHistologic subtype had no prognostic relevance in locoregional or systemic metastatic disease in appendiceal adenocarcinoma. In peritoneal metastases, mucinous histologic subtype was a favorable prognostic factor, compared to non-mucinous and signet ring cell subtype.     

CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study

Background: Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting.Patients and Methods: Efficacy and safety data were retrospectively collected from 25 patients with LBCL treated with CAR T-cells therapy at CHU de Québec-Université Laval. A literature search was then performed to identify other efficacy or safety data from a real-life setting. Results: At 3 months post infusion, the objective response rate (ORR) in our population with tisagenlecleucel and axicabtagene-ciloleucel were 20% and 47%, respectively. Bulky disease was the only negative predictor of poor response at 3 months (0% vs. 53%, P = .03). Bulky disease was associated with a median PFS of 2 months compared to 5 months for non-bulky disease (P = .0009). Grade ≥ 3 hematological toxicities were greater in patients treated with axi-cel (60% vs. 20%, P = .048), without bone marrow involvement (55% vs. 0%, P =.046), without stage IV disease (72% vs. 21%, P =.02), with refractory disease (67% vs. 10%, P =.01) or having been affected by cytokine release syndrome (58% vs. 0%, P =.02).Conclusion: The poor response rate at 3 months after infusion in our cohort was influenced mainly by bulky disease. Further studies are needed to better characterize the loss of efficacy of CAR T-cells because the majority of patients will relapse over time.     

Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group

IntroductionPancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments.MethodsRetrospective, national cohort-study from 7 medium-/high-volume centres in Austria, coordinated under the auspices of the Austrian Society of Surgical Oncology (ASSO).ResultsTwo-hundred patients underwent resection for pNEN, 177 had non-functioning tumours and 31 showed stage 4 disease. Participating centres were responsible for 2/3 of pNEN resections in Austria within the last years. The mean rate of completeness of variables was 98.6%. Ninety-days mortality was 3.5%, overall rate of complications was 42.5%. Morbidity did not influence long-term survival. The 5-year overall-survival (OS) was 81.3%, 10-year-OS 52.5% and 5-year recurrence-free-survival (RFS) 69.8%. Recurrence was most common in the liver (68.1%). Four out of five patients with recurrence underwent further treatment, most commonly with medical therapy or chemotherapy. Multivariable analysis revealed grading (HR:2.7) and metastasis (HR:2.5) as significant factors for relapse. Tumours-size ≥2 cm (HR:5.9), age ≥60 years (HR:3.1), metastasis (HR:2.3) and grading (HR:2.0) were associated with OS. Tumours <2 cm showed 93.9% 10-year-OS, but 33% had G2/G3 grading, 12.5% positive lymph-nodes and 4.7% metastasis at diagnosis, each associated with significant worse survival.ConclusionResection of pNENs in Austria is performed with internationally comparable safety. Analysed factors allow for risk-stratification in clinical treatment and future prospective trials. A watch-and-wait strategy purely based on tumour-size cannot be recommended.