Surgical Resection For Pancreatic Cancer Research Articles

Uncovering the clinicopathological features of early recurrence after surgical resection of pancreatic cancer

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.

The implications of sarcopenia in the treatment and prognosis of pancreatic cancer

Sarcopenia is the subclinical loss of skeletal muscle and strength and has been extensively studied in both cancer and surgical patients. Patients with sarcopenia are particularly vulnerable to major physiological stressors including surgery and surgical complications. Sarcopenia has thus gained significant recognition as an important prognostic factor for both complications and survival in cancer patients. The aim of this review was to evaluate the current literature on the effect of sarcopenia on the treatment and prognosis of pancreatic cancer. The prevalence of sarcopenia in pancreatic cancer patients range between 20 and 65% due to the heterogeneous groups of patients, difference in disease stage, and the different methods of measuring sarcopenia. Sarcopenia would be more accurately assessed by utilizing both imaging and clinical data, such as frailty. Although malnutrition could be responsible for the attenuated healing process of pancreatic anastomosis the relationship between sarcopenia and outcome following pancreaticoduodenectomy is debated. Most studies showed a higher risk of postoperative pancreatic fistula formation in patients with concurrent sarcopenia and high fat mass (sarcopenic obesity). Sarcopenia seems generally to be associated with lower survival. The assessment of sarcopenia can therefore lead to changes in management strategy, patient selection, and improved informed consent prior to surgical resection of pancreatic cancer. An improved prediction of clinically relevant pancreatic fistula formation after pancreatic surgery using preoperative computed tomography scan, including a fistula risk score using sarcopenic obesity and subcutaneous fat area will be useful. Although treatment for sarcopenia still remains an area of research a protocol to improve nutrition and fitness preoperatively may improve sarcopenia and surgical outcome.

Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis.

A greater than 1mm tumour-free resection margin (R0 >1mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial. Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively. Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies. After NAT, a tumour-free margin greater than 1mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.

HPB P24 Quality assurance within multicentre randomised controlled trials of surgical interventions for pancreatic cancer: a systematic review

Abstract Background Pancreatic cancer surgery is a complex intervention, with numerous studies exploring variations in approach to curative resection with the aim of improving outcomes. Multicentre randomised controlled trials (RCTs) represent the gold standard for evaluating these technical modifications. However, variations in how surgical intervention are delivered across trial sites and individual surgeons can influence results. Surgical quality assurance mechanisms within trial designs attempt to mitigate this by ensuring standardised, high-quality technique and reducing heterogeneity of procedures. This systematic review aimed to identify approaches to quality assurance within multicentre randomised controlled trials of surgical interventions for pancreatic cancer. Methods A systematic review was performed by searching MEDLINE and Embase databases between 1st January 2000 and 18th December 2022. Articles were deemed eligible for inclusion if they were a multicentre RCT and evaluated a surgical intervention, technique modification or variation in approach to surgical resection for pancreatic cancer. Data was extracted from included studies using a semi-structured form, with consideration of four prospectively defined quality assurance domains: i) surgical intervention and co-interventions description, ii) surgical technique standardisation, iii) performance monitoring methods, iv) surgeon/ unit credentialing methods. Results A total of 1970 studies were identified from the initial search, of which 44 trials were deemed eligible for inclusion. Thirty-six RCTs (81.8%) provided description of the intervention and/or co-intervention. Attempts to standardise technique were described in 33 RCTs (75.0%). However, only 4 trials (9.1%) deconstructed the intervention into its constituent components. Twelve studies (27.3%) described methods used to monitor performance and adherence to the intervention. The most common approaches used were intra-operative photographs (n=7; 15.9%), surgeon self-declaration (n=3; 6.8%), and pathological specimen review (n=2; 4.5%). Ten studies (22.7%) used credentialing methods based on unit entry criteria. Conclusions This study provides important data on the utilisation of methods of surgical quality assurance within pancreatic RCTs. With the exception of intervention description, compliance to the remaining domains of quality assurance was low. This may compromise the extent to which observed differences in clinical outcomes are due to the technique being evaluated within these trials. Confidence in the results of future RCTs would be improved by enhanced quality assurance across the four domains described.

The Implications of Sarcopenia in the Treatment and Prognosis of Pancreatic Cancer

Sarcopenia is the subclinical loss of skeletal muscle and strength and has been extensively studied in both cancer and surgical patients. Patients with sarcopenia are particularly vulnerable to major physiological stressors including surgery and surgical complications. Sarcopenia has thus gained significant recognition as an important prognostic factor for both complications and survival in cancer patients. The aim of this review was to evaluate the current literature on the effect of sarcopenia on the treatment and prognosis of pancreatic cancer. The prevalence of sarcopenia in pancreatic cancer patients range between 20% to 65% due to the heterogeneous groups of patients, difference in disease stage, and the different methods of measuring sarcopenia. Sarcopenia would be more accurately assessed by utilizing both imaging and clinical data, such as frailty. Although malnutrition could be responsible for the attenuated healing process of pancreatic anastomosis the relationship between sarcopenia and outcome following pancreaticoduodenectomy is debated. Most studies showed a higher risk of Postoperative Pancreatic Fistula (POPF) formation in patients with concurrent sarcopenia and high fat mass (sarcopenic obesity). Sarcopenia seems generally to be associated with lower survival. The assessment of sarcopenia can therefore lead to changes in management strategy, patient selection, and improved informed consent prior to surgical resection of pancreatic cancer. An improved prediction of clinically relevant pancreatic fistula formation after pancreatic surgery using preoperative Computed Tomography (CT) scan, including a fistula risk score using sarcopenic obesity and subcutaneous fat area will be useful. Although treatment for sarcopenia still remains an area of research a protocol to improve nutrition and fitness preoperatively may improve sarcopenia and surgical outcome.

Pathologic tumor response to neoadjuvant therapy in resected pancreatic cancer: does it affect prognosis?

Neoadjuvant therapy (NAT) + surgical resection for pancreatic cancer (PC) has gained consensus in recent years. Pathological response (PR) is generally assessed according to the College of American Pathologists grading system, ranging from 0 (complete response) to 3 (no response). The aim of our study is to evaluate the PR in a series of resections for PC after NAT and its prognostic implication. 112 patients undergone NAT and resection for PC between 2011 and 2020 were retrospectively evaluated. PR was 0/1, 2 and 3 in 18 (15%), 79 (61%) and 29 (24%) cases, respectively. Chemotherapy regimens different from FOLFIRINOX and gemcitabine + nab-paclitaxel (OR 11.61 (2.53-53.36), p = 0.002) and lymphovascular invasion (OR 11.28 (1.89-67.23), p = 0.008) were associated to PR-3. Median follow-up was 25.8 (3.6-130.5) months. For PR-0/1, PR-2 and PR-3, median DFS was 45.8, 11.5, 4.6months (p < 0.0001), respectively, while median OS was not reached, 27.1 and 17.5months (p = 0.0006), respectively. At univariate analysis, PR-0/1 was significantly associated to better DFS and OS (HR 0.33 (0.17-0.67), p = 0.002; HR 0.20 (0.07-0.54), p = 0.002, respectively). At multivariate analysis, pancreaticoduodenectomy (HR 0.50 (0.30-0.84), p = 0.009), LNR (HR 27.14 (1.21-608.9), p = 0.038) and lymphovascular invasion (HR 1.99 (1.06-3.76), p = 0.033) were independently associated to DFS; pre-treatment CA 19.9 value (HR 1.00 (1.00-1.00), p = 0.025), post-treatment resectability status (HR 0.51 (0.28-0.95), p = 0.035), pancreaticoduodenectomy (HR 0.56 (0.32-0.99), p = 0.050), severe morbidity (2.99 (1.22-7.55), p = 0.017), LNR (HR 56.8 (2.08-1548.3), p = 0.017), lymphovascular invasion (HR 2.18 (1.08-4.37), p = 0.029) were independently associated to OS. PR did not reach statistical significance at multivariate analysis. A favorable PR is observed only in a limited number of cases. The prognostic role of PR, despite being promising, remains unclear and further multicentric studies are needed.

Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer.

Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.

An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.

TPS771 Background: Curative treatment for potentially resectable (resectable or borderline resectable) pancreatic adenocarcinoma, despite recent advances, leads to only suboptimal outcomes. Recent US national cooperative group trials have demonstrated the safety and feasibility of neoadjuvant chemotherapy (PMID 33475684, PMID 35834226), and also show that the two frontline regimens, FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP), are comparable in this setting. Finally, ability to undergo resection remains the key driver of cure. Therefore, an approach that selects chemotherapy based on early response assessment, to maximize the probability of resection, is likely to improve curative outcomes. Methods: This is a phase II study intended to maximize the probability of surgical resection for pancreatic cancer. Key eligibility requirements include adult patients with a confirmed histopathologic diagnosis of pancreatic carcinoma or adenocarcinoma, an ECOG PS ≤ 1, resectable or borderline resectable disease by central radiology review, no prior therapy for index pancreatic cancer, and adequate bone marrow, liver and kidney function. Treatment includes 4 doses (~ 2 months total treatment time) of FOLFIRINOX (“Chemo1”). After a re-evaluation, using radiologic response, CA19.9 response, and chemotherapy toxicity, patients will either continue with “Chemo1” for another 4 cycles (8 doses) or switch to GnP (“Chemo2”) which will be administered for 4 cycles (12 doses, for ~4 month total treatment time), followed by surgical resection. Primary outcome will measure the proportion of patients undergoing surgical resection using historical dated compared to 32 patients in a current study with a time frame of 16 months. Using historical data, the expected proportion of patients undergoing resection is ~60%. The goal of this study is to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, 32 patients will be needed to demonstrate this difference. Key translational correlatives will include serial circulating tumor DNA assessment and extensive tumor molecular profiling. Clinical trial information: NCT04594772 .

Role of perioperative over neoadjuvant chemotherapy after surgery in pancreatic cancer: NCDB analysis

Background: There is increasing adoption of neoadjuvant chemotherapy in patients undergoing surgical resection for pancreatic cancer (PC) to ensure receipt of systemic therapy in addition to surgery for optimal outcomes. However, with receipt of systemic treatment in neoadjuvant setting, the role of giving adjuvant chemotherapy in addition to neoadjuvant i.e., perioperative chemotherapy, remains controversial.

Short- and long-term outcomes of pancreatectomy in patients with hemodialysis.

Several reports have shown the high mortality rate of pancreatic resection in patients with hemodialysis (HD), however, its long-term outcome remains unclear. In this study, we examined cases of pancreatic resection in patients with HD and conducted a literature review. Four patients with HD who underwent pancreatic resection from 2004 to 2019 were enrolled. To compare the clinicopathological variables of HD and non-HD patients, 161 non-HD patients who had undergone surgical resection for pancreatic cancer were enrolled. Among four cases of pancreatic resection with HD, three cases were malignant diseases. All patients with HD had some co-morbidities (100% in HD group, 45.3% in the non-HD group) and postoperative complications (100% in the HD group, vs 46.6% in the non-HD group). Although one patient had severe postoperative complications and length of postoperative hospital stay was longer, the 30- and 90-day mortality rates were both 0% in patients with HD. However, three cases in the HD group (75%) died approximately 6 months after surgery, including one cancer-related death. Pancreatic surgery in patients with HD should be carefully indicated, especially pancreaticoduodenectomy or total pancreatectomy, because of the poor prognosis induced by non-cancer-related causes of death. J. Med. Invest. 70 : 105-109, February, 2023.

Association of Textbook Outcome and Surgical Case Volume with Long-Term Survival in Patients Undergoing Surgical Resection for Pancreatic Cancer.

Journal of the American College of Surgeons ():10.1097/XCS.0000000000000749, May 09, 2023. | DOI: 10.1097/XCS.0000000000000749

Association of Textbook Outcome and Surgical Case Volume with Long-Term Survival in Patients Undergoing Surgical Resection for Pancreatic Cancer.

Current literature has identified textbook outcome (TO) as a quality metric after cancer surgery. We studied whether TO after pancreatic resection has a stronger association with long-term survival than individual hospital case volume. Patients undergoing surgery for pancreatic adenocarcinoma from 2010 to 2015 were identified from the National Cancer Database. Hospitals were stratified by volume (low less than 6, medium 6 to 19, and high 20 cases or more per year), and overall survival data were abstracted. We defined TO as adequate lymph node count, negative margins, length of stay less than the 75th percentile, appropriate systemic therapy, timely systemic therapy, and without a mortality event or readmission within 30 days. The association of TO and case volume was assessed using a multivariable Cox regression model for survival. Overall, 7270 patients underwent surgery, with 30.7%, 48.7%, and 20.6% performed at low-, medium-, and high-volume hospitals, respectively. Patients treated at low-volume hospitals were more likely to be Black, be uninsured or on Medicaid, have higher Charlson comorbidity scores, and be less likely to achieve TO (23.4% TO achievement vs 37.5% achievement at high-volume hospitals). However, high hospital volume was no longer associated with overall survival once TO was added to the multivariable model stratified by volume status. Achievement of TO corresponded to a 31% decrease in mortality (hazard ratio 0.69; p < 0.001), independent of hospital volume. Improved long-term survival after pancreatic resection was associated with TO rather than high hospital volume. Quality improvement efforts focused on TO criteria have the potential to improve outcomes irrespective of case volume.

Preoperative Rapid Weight Loss as a Prognostic Predictor After Surgical Resection for Pancreatic Cancer.

The aim of the study is to evaluate the influence of cachexia at the time of diagnosis of pancreatic ductal adenocarcinoma (PDAC) on prognosis in patients undergoing surgical resection. Patients with data on preoperative body weight (BW) change followed by surgical resection during 2008-2017 were selected. Large BW loss was defined as weight loss >5% or >2% in individuals with body mass index less than 20 kg/m2 within 1 year preoperatively. Influence of large BW loss, ΔBW defined as preoperative BW change (%) per month, prognostic nutrition index, and indices of sarcopenia. We evaluated 165 patients with PDAC. Preoperatively, 78 patients were categorized as having large BW loss. ΔBW was ≤ -1.34% per month (rapid) and > -1.34% per month (slow) in 95 and 70 patients, respectively. The median postoperative overall survival of rapid and slow ΔBW groups was 1.4 and 4.4 years, respectively (P < 0.001). In multivariate analyses rapid ΔBW (hazard ratio [HR], 3.88); intraoperative blood loss ≥430 mL (HR, 1.89); tumor size ≥2.9 cm (HR, 1.74); and R1/2 resection (HR, 1.77) were independent predictors of worse survival. Preoperative rapid BW loss ≥1.34% per month was an independent predictor of worse survival of patients with PDAC.

Stereotactic Body Radiation Therapy is Safe and Feasible for the Treatment of Locally Recurrent Pancreatic Adenocarcinoma after Curative Resection

<h3>Purpose/Objective(s)</h3> Locoregional relapse rates following surgical resection of pancreatic cancer can be as high as 45-50%. The majority of these patients are not candidates for re-resection due to co-morbidities and/or technically unresectable disease, highlighting the role of non-invasive options such as radiation therapy. The purpose of this study was to report on a cohort of radiation-naïve patients who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> Patients who were treated with SBRT for locally recurrent pancreatic cancer after initial curative resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate and multivariate analyses were performed to identify variables associated with clinical outcomes. Kaplan-Meier analysis was performed for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. <h3>Results</h3> From September 2012 to November 2018, a total of 19 patients were treated with SBRT for locally recurrent pancreatic cancer after initial surgical resection. No patients had prior radiation. The most common SBRT dose/fractionation was 33 Gy in 5 fractions (12/19, 63.1 %), followed by 25 Gy in 5 fractions (4/19, 21.0%), 28 Gy in 5 fractions (1/19, 5.3%), 27 Gy in 4 fractions (1/19, 5.3%), and 26.4 Gy in 4 fractions (1/19, 5.3%). Peri-SBRT chemotherapy was administered to 10 patients, in the pre-SBRT (3/19, 15.7%) and/or post-SBRT (8/19, 42.1%) setting. Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. A total of 9 patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field, involving the porta hepatis (n=1), pancreaticojejunostomy (n=1), and pancreatic remnant (n=1). Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A biologically effective dose (BED₁₀) < 54.8 Gy was associated with inferior LPFS (1-year LPFS, 25.0% vs 80.2%, p<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4-5 toxicity events. <h3>Conclusion</h3> Stereotactic body radiation therapy for local recurrence after initial curative resection is safe and feasible. A BED₁₀ < 54.8 Gy was significantly associated with inferior local control, and one-third of local failures were out-of-field. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.

Prognostic Impact of Lymphocyte-to-C-Reactive Protein Ratio in Patients Who Underwent Surgical Resection for Pancreatic Cancer.

Increasing evidence indicates that increased systemic inflammation is correlated with poorer cancer-specific survival in various cancer types. This study aimed to evaluate the prognostic value of various combinations of inflammatory factors in patients who underwent surgical resection for pancreatic cancer (PC). We retrospectively analyzed 97 consecutive patients with PC who underwent pancreatectomy. We assessed the predictive impact for recurrence using a combination of 5 inflammatory markers and focused on the lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses using the Cox proportional hazards model. Low preoperative LCR was correlated with low serum hemoglobin, low serum albumin concentration, high frequency of microscopic vascular invasion, and high frequency of microscopic perineural invasion. The low LCR group had significantly worse RFS and OS. Lower preoperative LCR was an independent predictor of shorter RFS and OS in this cohort. Preoperative LCR is a novel and convenient prognostic marker for patients with PC. Patients with low LCR may require more favorable intensive therapy.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BackgroundIt is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC.MethodsPatients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts – patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS).Results3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05).DiscussionReceipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Quality of Life after Pancreatic Surgery - A Systematic Review

Introduction: Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. The impact of surgical resection on health-related quality of life (HRQOL) is an important outcome measure. Hence, this study aims to assess short- and long-term HRQOL after surgical resection of pancreatic cancer.

Pancreatic Cancer

Pancreatic cancer ranks 4th among men and 3rd among women in terms of cancer-related deaths according tothe Cancer Information Service of the National Cancer Center website. The morbidity and mortality are similar,the mortality rate when affected is very high, and the 5-year survival rate for all pancreatic cancer cohorts is 5% to10%, which is the poorest prognosis among several malignant diseases. However, there is much room for improving treatment outcomes.Surgical resection is the only treatment that can be expected to cure pancreatic cancer, but the recurrence rateafter curative resection is very high. It is often the case that it is already unresectable at the time of diagnosis.Regarding surgical resection, despite various surgical improvements, the 5-year survival rate of surgery alone remains at approximately 10% to 20%, and chemotherapy is used not only in unresectable cases but also in resectedcases. The importance of multidisciplinary treatment is increasing.The paper outlines the significance of surgical resection for pancreatic cancer, the evolution of chemotherapy,and future prospects.

Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: a diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle aspiration

BackgroundA pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified.AimsTo evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer.MethodsBetween January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis.ResultsThe diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) (p < 0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) (p = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not.ConclusionsEUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.

Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer

ABSTRACT Background The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called “liquid biopsy”) is recently developed. Aims Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. Methods A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. Results KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36–9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). Conclusions In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.