Resectable Periampullary Cancer Research Articles

Surgical site infection following pancreaticoduodenectomy in a referral cancer center in Mexico

BackgroundPancreaticoduodenectomy is the standard treatment for resectable periampullary cancer. Surgical site infections (SSI) are common complications with increased morbidity. The study aimed to describe the prevalence, risk factors, microbiology, and outcomes of SSI among patients undergoing pancreaticoduodenectomy. MethodsWe conducted a retrospective study in a referral cancer center between January 2015 and June 2021. We analyzed baseline patient characteristics and SSI occurrence. Culture results and susceptibility patterns were described. Multivariate logistic regression was used to determine risk factors, proportional hazards model to evaluate mortality, and Kaplan-Meier analysis to assess long-term survival. ResultsA total of 219 patients were enrolled in the study; 101 (46%) developed SSI. Independent factors for SSI were diabetes mellitus, preoperative albumin level, biliary drainage, biliary prostheses, and clinically relevant postoperative pancreatic fistula. The main pathogens were Enterobacteria and Enterococci. Multidrug-resistance rate in SSI was high but not associated with increased mortality. Infected patients had higher odds of sepsis, longer hospital stay and intensive care unit stay, and readmission rate. Neither 30-day mortality nor long-term survival was significantly different between infected and non-infected patients. ConclusionsSSI prevalence among patients undergoing pancreaticoduodenectomy was high and largely caused by resistant microorganisms. Most risk factors were related to preoperative instrumentation of the biliary tree. SSI was associated with greater risk of unfavorable outcomes; however, survival was unaffected.

Efficacy of sequential perioperative FOLFIRNOX plus gemcitabine nab-paclitaxel for resected pancreatic and periampullary cancers.

724 Background: Perioperative chemotherapy with single regimen either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (Gem/NabP) is the current standard of care for pancreatic and periampullary cancers (PC) with overall survival (OS) of 2-3 years without pre-selected CA19-9 level. Sequential chemotherapy with FFX plus Gem/NabP has recently been investigated in metastatic PC and shown to improve OS. We investigated the outcome of patients who received sequential perioperative chemotherapy FFX plus Gem/NabP. Methods: Patients treated with curative intent surgery for PC who received perioperative sequential chemotherapy FFX plus Gem/NabP (each regimen was given at least two months) were identified. OS and recurrence-free survival (RFS) were calculated from the date of initial treatment (neoadjuvant chemotherapy or resection) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 29 patients were identified: 24 (83%) patients had pancreatic cancer, 5 (17%) patients had periampullary cancer; 16 (55%) patients received neoadjuvant chemotherapy FFX plus Gem/NabP; 13 (45%) patients underwent upfront surgery and received adjuvant FFX plus Gem/NabP chemotherapy; 22 (76%) patients had resectable disease, the rest 7 (24%) patients had borderline or unresectable disease were all in the neoadjuvant cohort; node positivity was higher in the adjuvant cohort (n=8, 62%) than in the neoadjuvant cohort (n=8, 50%); 5 (17%) patients were found to have homologous recombination deficiency (HRD: BRCA2, CHEK, BARD, ATM) and received PARP inhibitors as part of the perioperative therapy combination. 10 (34%) patients had CA19-9 ≥ 500. Median age was 65 years (range, 45-79 years), 20 (69%) were male. During the study period, 4 (14%) patients died, and 6 (21%) patients had disease recurrence. Median RFS and OS were not reached with a median follow-up of 28 months (range, 10.9–119 months). The longest RFS was 10 years. The 2-years RFS and OS for the entire cohort was 76.7% and 88.8%, respectively. There was no statistical difference in RFS (log rank HR 1.72, 95% CI 0.23-13.15) or OS (log rank HR 0.99, 95% CI 0.20-4.93) for patients in the neoadjuvant cohort versus adjuvant cohort. Conclusions: Sequential perioperative chemotherapy combined FFX plus Gem/NabP for resected PC is effective and potentially prolongs survival, compared to historical controls who received single regimen.[Table: see text]

Postoperative outcomes of resectable periampullary cancer accompanied by obstructive jaundice with and without preoperative endoscopic biliary drainage.

Preoperative biliary drainage (PBD) is useful in resectable periampullary cancer with obstructive jaundice. Whether it is better than direct surgery (DS) in terms of postoperative complications and mortality is controversial. All cases of successful pancreaticoduodenectomy (PD) in patients with periampullary cancer with obstructive jaundice performed between January 2016 and January 2021 were retrospectively reviewed. Endoscopic PBD was performed; data pertaining to serum bilirubin level, procedural technique, and duration before surgery were obtained. The incidence of postoperative complications and survival rate were compared between the PBD and DS group. A total of 104 patients (PBD, n = 58; DS, n = 46) underwent curative PD. The mean age was 63.8 ± 10 years and 53 (51%) were male. Age, body mass index (BMI), sex, Eastern Cooperative Oncology Group status, presence of comorbid disease, initial laboratory results, and pathological diagnoses were not significantly different between the two groups. The incidence of postoperative complications was 58.6% in the PBD group while 73.9% in the DS group (relative risk [RR] 1.26, 95% confidence interval [CI] 0.92, 1.73, p=0.155) and the difference was not significant except in bile leakage (RR 8.83, 95% CI 1.26, 61.79, p = 0.021) and intraoperative bleeding (RR 3.97, 95% CI 0.88, 17.85, p = 0.049) which were higher in the DS group. The one-year survival rate was slightly less in the DS group but the difference was not statistically significant. The independent predictors for death within 1-year were intraoperative bleeding and preoperative total bilirubin > 14.6 mg/dL. PBD in resectable malignant distal biliary obstruction showed no benefit in terms of 1-year survival over DS approach. But it demonstrated the benefit of lower risks of intraoperative bleeding, and bile leakage. Additionally, the level of pre-operative bilirubin level of over 14.6 mg/dL and having intraoperative bleeding were associated with a lower 1-year survival in such patients. Overall, PBD may be not necessary for all resectable periampullary cancer patients, but there might be a role in those with severely jaundice (>14.6 mg/dL), as it helps lower risk of intraoperative bleeding, and might lead to a better survival outcome.

Can we recommend surgical treatment to the octogenarian with periampullary cancer?:National database analysis in South Korea.

The incidence of periampullary cancer in the elderly is increasing. Safety and oncologic effectiveness of pancreaticoduodenectomy in elderly patients is still controversial. From 2002 to 2016, patients with periampullary cancer were evaluated. Customised health information data provided by the National Health Insurance Corporation (NHIS-2018-1-157) were used for analysis. Chronological changes in the incidence of periampullary cancer and long-term survival outcomes were estimated according to patients' age. A total of 148,080 patients were found to have periampullary cancer. Chronologically, the incidence of periampullary cancer increased, and the proportion of elderly patients with periampullary cancer prominently increased (about 2.1 times in patients in their 70s and about 4.7 times in those older than 80 years). The number of patients with pylorus-preserving pancreaticoduodenectomy in their 70s (about 5.6 times, p<0.001) and over 80 years of age (about 8.9 times, p<0.001) was much higher than the number of patients aged younger than 50 years (about 1.7 times) and in their 60s (about 2.5 times). Long-term survival was different as per diagnosis (p<0.001). In addition, it was observed that age was a factor attenuating the survival of patients with resected periampullary cancers (p<0.001). However, in caseof patients older than 80 years, those who underwent surgical treatment showed a higher survival rate than those who did not undergo surgical treatment. We can recommend surgical treatment for elderly patients with resectable periampullary cancer. The survival data in this study can be useful references especially in making treatment plan for octogenarians diagnosed with periampullary cancer.

Predictive Power of Preoperative Serum Total Bilirubin for the Outcomes Following Pancreaticoduodenectomy

Background: The high levels of bilirubin in patients with periampullary cancers may increase the morbidity or mortality after curative surgery. Objectives: We aimed at evaluating the predictive power of preoperative serum total bilirubin for the outcomes after pancreaticoduodenectomy (PD) in resectable periampullary cancers. Methods: The data of 80 patients, who had undergone PD, were retrospectively analyzed. Regarding the preoperative bilirubin, we opted for 20 mg/dL as the cut-off value to divide patients into two groups to be subjected to simple and multiple logistic regression. Results: A total of 80 patients with a mean age of 54.90 ± 14.33 years underwent PD. The median preoperative bilirubin level was 4.7 mg/dL and the majority of cases (88.8%) had bilirubin &lt; 20 mg/dL. While there was no significant difference in the mortality between bilirubin groups (P = 0.266), bilirubin≥20 mg/dL remarkably increased the postoperative morbidity (P = 0.012, Odds ratio = 3.04); 57.5% of cases underwent biliary drainage before surgery, which did not impact the mortality and morbidity. Multiple analysis by a logistic regression model disclosed that the only statistically significant variable for mortality was the total operative time (P = 0.038) and among all factors, total bilirubin level was the only independent predictor for the morbidity status (P = 0.009). Conclusions: This study suggested that preoperative biliary drainage should only be limited to patients with high bilirubin levels (≥ 20 mg/dL) or expected delayed surgeries.

147 Pancreatoduodenectomies: a Single Center's Perspective into the Epidemiology and Surgical Outcomes of Periampullary and Pancreatic Cancers in South India.

Pancreatoduodenectomy (PD) is the only curative procedure for resectable periampullary cancers. This study aims to survey the various outcome variables of the procedure at our institute, which is in the early process of evolving into a high-volume center for PDs. Data of patients, who underwent PDs, was collected retrospectively from January 2010 to December 2017 and prospectively from January 2018 to December 2019. Various preoperative, intraoperative, and histopathological parameters were compared with the outcome variables-morbidity and mortality rates. A total of 147 patients underwent PDs over the last decade. From January 2010 to December 2014 (period A), 29 patients underwent PD, while 118 patients underwent PD from January 2015 to December 2019 (period B). Clinically relevant (CR) delayed gastric emptying (44.8% vs 23.7%), CR post-pancreatectomy hemorrhage (37.9% vs 18.6%), and blood loss (850 ml (400-5300 ml) vs 600 ml (150-2500 ml)) improved in period B with no improvement in CR postoperative pancreatic fistula (20.7% vs 28.8%). The rates of SSI (63.6%), pulmonary complications (29.9%), and mean postoperative stay (19.87 ± 11.59 days) were found to be higher than most of the major centers. Mortality rates decreased significantly from 27.6% in period A to 10.2% in period B (p = 0.029). Median overall survival was 30 months (95% CI 20.76-39.23 months) CONCLUSION: Over the last decade, there has been a significant improvement in the mortality rate, but morbidity remains high and must be looked into as the department enters the new decade as a young high-volume center.

A multicenter prospective randomized controlled trial for preoperative biliary drainage with uncovered metal versus plastic stents for resectable periampullary cancer.

Although routine preoperative biliary drainage (PBD) in patients with distal malignant biliary obstruction is generally not recommended, there are still various situations where it may be necessary. The current study aims to compare the uncovered self-expandable metal stent (uSEMS) and plastic stent (PS), where PBD may be necessary. In this multicenter prospective randomized study, patients with resectable periampullary cancer with cholangitis, deep jaundice, or expected long waiting time for surgery were included. PBD was performed endoscopically, but percutaneous drainage was allowed if the initial endoscopic drainage was not feasible. The primary outcome was the reintervention rate; the secondary outcomes were the complication rates, rate of decrease of total bilirubin, waiting time for surgery, and postoperative hospital stay. Of the 60 enrolled patients, 53 were included for analysis (26 PS and 27 uSEMS). Common bile duct cancer was the most common (27, 50.9%), followed by pancreatic head cancer (20, 37.7%). Regarding PBD indication, 36 (67.9%) had cholangitis and 21 (39.6%) had a total bilirubin level of more than 10mg/dL at randomization; 10 (18.9%) were included due to delayed surgery by more than 7days. Fifty (94.3%) patients received pancreaticoduodenectomy, and one (1.9%) patient received palliative hepaticojejunostomy. The median waiting time for surgery was 11.0days. There was no difference in the reintervention rate (3.8% and 3.8% in PS and uSEMS, P>.999), PBD-related complication rate (23.1% and 22.2%, P>.999), PBD- or surgery-related complication rate (57.7% and 48.1%, P=.674), and the rate of decrease of total bilirubin (P=.541). The median hospital stay after surgery was 13.0days without significant difference. For patients who received surgery within the first 2weeks from receiving PBD, there was no superiority of uSEMS to PS. According to the expected waiting time for surgery, selective approach for stent choice should be considered.

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial

Aims: To investigate whether preoperative enteral diets ­enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized ­controlled trial. Methods: Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Results: Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). Conclusions: The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD.

Preoperative biliary drainage adversely affects surgical outcomes in periampullary cancer: a retrospective and propensity score-matched analysis.

The use of preoperative biliary drainage (PBD) for managing patients with periampullary cancer awaiting surgery remains controversial. The impact of PBD status and type on surgical outcomes has not been established, leading to a lack of consensus. We aimed to evaluate the impact of PBD on short-term surgical outcomes in curatively resected periampullary cancer. We retrospectively reviewed data from patients undergoing curative periampullary cancer resection. A propensity score-matched analysis was performed to adjust for clinical differences. Univariate and multivariate analyses were performed to determine independent risk factors for complications. The overall complication rate was significantly higher in patients who underwent PBD (P=0.027). Additionally, complication rates were significantly higher in the endoscopic biliary drainage (EBD) group than in the percutaneous transhepatic biliary drainage (PTBD) group (P<0.001). After propensity score matching, overall complication rates in patients receiving EBD (P<0.001) were significantly higher. PBD type and diagnosis were independent risk factors for complications (hazard ratios: 1.927 for EBD; 1.921 for biliary tract cancer). Preoperative biliary drainage, especially EBD, should not be routinely performed in patients awaiting surgery for periampullary cancer, as it increases the risk of complications.

Ampullary cancer of intestinal origin and duodenal cancer - A logical clinical and therapeutic subgroup in periampullary cancer.

Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary (16%-50%), bile duct (5%-39%), and duodenal cancer (3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival (29-47 mo and 22-54 mo) compared to pancreatic cancer (13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.

Early liver metastases in resectable periampullary cancer: Incidence and risk factors

PurposeThe aim of the present study was to estimate the incidence of very early hepatic metastases (HMs) (<6 months) and their imaging patterns after cephalic duodenopancreatectomy (CDP) for periampullary carcinoma (excluding duodenal carcinoma) and to identify their associated risk factors. MethodsFrom January 2003 to June 2016, all patients who underwent surgical treatment for periampullary carcinoma by CDP at our institution and with adequate pre- and postoperative CT scans were included. Univariate and multivariate logistic regressions were performed to determine factors associated with very early HM and recurrence. ResultsOf the 132 patients included retrospectively, 27 (20.5%) patients developed HMs. The mean time to diagnosis of HM was 103.9±55.2days. HMs were multiple in 81.4% of cases and bilobar in 59.3% of cases; their mean maximum size was 16.7±12.7mm.In univariate logistic analysis, lymphovascular emboli were significantly associated with HM (p=0.02). No independent risk factors for HM were found in multivariate analysis. In multivariate logistic analysis, two independent risk factors were identified for the occurrence of early recurrence: tumor size >23mm on preoperative CT scan (OR: 3.3; 95% CI: [1.2–9.3]; p=0.02) and tumor differentiation (poor vs. good: OR 15.5; 95 CI [1.5–158.3]; moderate vs. good: OR: 17.1; 95% CI: [1.9–154.4]; p=0.04). ConclusionsNearly one in five patients developed HM after CDP within 6 months with a highly consistent pattern. A thorough preoperative assessment, combining CT scan and MRI with a delay of less than three weeks before surgery, appears essential. A routine systematic postoperative CT scan at 8 weeks is also required prior to initiating adjuvant chemotherapy.The type of surgical intervention does not seem to be a risk factor, although the risk of HM occurrence appears to be related to the lymphovascular invasion of the tumor and maybe its degree of differentiation, elements not assessable by imaging.

Meta-analysis of adjuvant therapy following curative surgery for periampullary adenocarcinoma.

Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers. A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events. A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not. This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.

Posterior Superior Mesenteric Artery (SMA) First Approach vs. Standard Pancreaticoduodenectomy in Patients with Resectable Periampullary Cancers: a Prospective Comparison Focusing on Circumferential Resection Margins

The 'SMA-first' (P-SMA) pancreatoduodenectomy (PD) allows dissection directly on the right lateral aspect of superior mesenteric artery (SMA) which may decrease circumferential resection margin (CRM) positivity. This comparative study between standard PD (sPD) and P-SMA approach was planned focusing on CRM involvement. This was a prospective study comparing consecutive patients with resectable periampullary cancers (PACA) undergoing PD using the standard or P-SMA approach. The perioperative outcomes and the CRM positivity rates (specimens analysed according to the standardized Leeds pathology protocol (LEEPP)) were compared. Overall, 39 patients (28 men; mean age 54years; sPD 21, P-SMA 18) were included. Both groups were comparable with regard to demographic/tumour characteristics and perioperative outcomes. The P-SMA technique was significantly faster (321.1±54.0 vs. 357.6±55.8min; p=0.05). Though the mean tumour size (2.2 vs. 2.1cm; p=0.84) and T stage (T2 and T3) distribution were similar in both groups, lymph node yield was significantly higher in the P-SMA group (10.7 vs. 5.95; p=0.001; mean 8 (2-21)). Though CRM positivity (margin <1mm) occurred in 8 (21.1%), we did not find the P-SMA PD to yield significantly lower CRM positivity rates compared to the sPD (3/17 (17.6%) vs. 5/21(23.8%); p=0.71). At a median follow-up of 28months, fewer patients in the P-SMA PD group developed recurrence (2/15 vs. 5/19; p=0.3) or died (3/15 vs. 7/19; p=0.19), though this difference was not significant. In patients with resectable PACA, P-SMA PD was significantly faster and yielded higher lymph node counts in the specimen but did not lower the rate of CRM positivity as determined by the LEEPP.

Pancreatoduodenectomy for periampullary cancer and biliary obstruction: impact of a pathway to avoid preoperative biliary drainage

BackgroundRandomised trials have shown that preoperative biliary drainage (PBD) causes more harm than a straight to surgery approach for patients with jaundice and periampullary malignancy. However, it remains standard practice in many centres for jaundiced patients to undergo PBD. The aim of this study was to review the impact of a pathway to avoid PBD before pancreatoduodenectomy on clinical outcomes. MethodsA pathway to avoid PBD was implemented at the start of the study period (August, 2015). A dedicated nurse specialist and surgeon visited each referring trust to raise awareness of the pathway. Inclusion criteria were patients with resectable periampullary cancers and jaundice; patients were selected for surgery without PBD if they had not undergone PBD before referral and bilirubin concentration did not exceed 450 μmol/L. Time from initial CT scan to referral to multidisciplinay team discussion to specialist clinic and surgery were recorded. FindingsOver 12 months, 61 and 32 patients underwent pancreatoduodenectomy with and without PBD, respectively. 58 patients in the PBD group (95%) had undergone PBD before referral. There was no difference in demographic data or tumour types between the two groups. The duration of key intervals from referral to surgery were all shorter in the no PBD group than in the PBD group (median total duration 16 days [IQR 8–39] vs 65 [9–181], p<0·0001). Significantly more patients underwent pancreatoduodenectomy (31/32 vs 46/61, p=0·009) and venous resection (10/31 vs 4/46, p=0·014) in the no PBD group than in the PBD group. The sensitivity of initial staging CT for correctly staging resectable locally advanced disease was 91% and 50% in the no PBD and PBD groups, respectively (p=0·042). The accuracy of the initial CT scan to define locally advanced resectable disease was worse in the PBD group, presumably related to the difference in time between CT and surgery. Furthermore, average costs of treatment between presentation and surgery were £3178 cheaper in the no PBD group. InterpretationEarly surgery to avoid PBD is possible within the National Health Service. By reducing the time to surgery more patients undergo potentially curative surgery and costs of treatment are reduced. An understanding about why surgery without PBD is not done routinely is needed, as is the development of strategies to support its more widespread practice. FundingPancreatic Cancer UK.

Over 700 Whipples for Pancreaticobiliary Malignancies: Postoperative Morbidity Is an Additional Negative Prognostic Factor for Distal Bile Duct Cancer

BackgroundDistal cholangiocarcinomas and pancreatic cancers both arise from pancreaticobiliary epithelium. Despite their common origin, there is a possible discrepancy in outcome. We analysed the surgical, pathological and survival outcome of resected distal cholangiocarcinoma compared with pancreatic cancer. MethodsAll cases of resected distal cholangiocarcinoma and pancreatic cancer from 1998 to 2014 were extracted from our database. Outcomes were compared. ResultsThere were 54 (7.6%) cases of cholangiocarcinoma and 656 (92.4%) pancreatic cancer. Cholangiocarcinoma showed lower T and N stage, lymphatic and perineural invasion (p < 0.05), worse surgical outcome (p < 0.05) and less access to adjuvant therapy if compared with pancreatic cancer (72.7 vs. 83.1%, p = 0.05). Both showed a similar disease-specific survival (35 vs. 29 months, p = 0.3). Independent predictors of prognosis for pancreatic cancer were resection margin, grading, perineural invasion, T and N status, whereas for cholangiocarcinoma were grading and occurrence of POPF. ConclusionConsidering a large cohort of resected periampullary cancers, cholangiocarcinoma is extremely rare. An earlier diagnosis is associated with better pathological predictors of outcome but increased postoperative morbidity compared to pancreatic cancer, particularly POPF. Consequent decrease in the access to adjuvant therapy for complicated cholangiocarcinoma might explain why survival is as poor as for pancreatic cancer.

Prospective randomized controlled trial comparing laparoscopic versus open pancreaticoduodenectomy for malignant periampullary and pancreatic head lesions

Background: Current literature supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an alternative to open pancreaticoduodenectomy (OPD) for pancreatobiliary malignancies. Studies done so far are case series and matched comparisons; a randomized trial analysing two has not been reported. Materials and method: Trial included 64 patients with resectable peri-ampullary or pancreatic head cancer, randomized by computer generated random numbers into either LPD or OPD group during September 2013 to August 2015. Sample size was 32 in each arm, assuming power of study 80% & type I error of 0.05. Primary outcome measure was hospital stay, secondary outcome measures were blood loss, operation time, pathological radicality and complication rate. Results: Mean operative time 260.2 min (±11.10) in OPD, 359.4 min (±13.84) in LPD (p = 0.0308). Mean blood loss 300.6 ml (±46.56) in OPD, 249.8 ml (±22.33) in LPD (p<0.001). Conversion rate of 3.1%. The median length of stay in OPD was 12 days (6–30), LPD of 8 days (5–52) (p = 0.0001). Pancreatic fistula 18.75% in OPD; 15.60% in LPD (p = 0.314), overall complications (Clavien Dindo) 31.25% in OPD; 25% in LPD (p = 0.755) and 3.1% mortality in each arm. Mean nodes retrieved in OPD 17.00 (±1.47), LPD 18.97 (±1.0) with 0.95 CI, p = 0.059. Conclusion: This study establishes safety of LPD in terms of short term outcomes, complications, mortality and oncological radicality to that of OPD, has benefits of shorter hospital stay, reduced blood loss and lesser wound complications. Comparisons in terms of disease free survival and long term survival remains to be seen (NCT02081131).

The impact of adjuvant delayed radiotheraphy (RT) on survival in patients with resected periampullary adenocarcinomas.

e15168 Background: Postoperative prognosis for ampullary carcinoma (AC) is superior to that of pancreatic cancer (PC), the former exhibiting higher complete surgical resection, lower recurrence and longer survival rates (1). Despite all the major recent advances in surgery, chemotherapy (CT) and RT, PC is still one of the most lethal malignancies, overall survival (OS) rates being as low as 5% at 5 years (2). This study was intended to evaluate survival in patients with resected periampullary cancer treated with adjuvant Gemcitabine (Gem) and cisplatin (Cis) with or without delayed RT (with Gem). Methods: This retrospective study involved 91 patients diagnosed and treated with periampullary cancer. Patients with adenocarcinoma of periampullary region with gross total tumor resection and lymph node dissection (R0 and R1 resections only) were included. Of 59 patients with PC, 38 received Gem and Cis for 3 cycles (3 months) before CRT. When delivered after Gem /RT, Gem and Cis were usually given for another 1-3 cycles. Twenty-seven patients received Gem and Cis alone over 6 cycles. Of 32 patients with non-pancreatic periampullary 23 received CT+CRT and 9 patients received CT alone. Results: Patients with non-pancreatic periampullary cancer had better OS (p:0.017) and disease free survival (DFS) ( p&lt;0.001 ) compared to patients with PC. Median OS of patients with PC was 21 months. Both OS and DFS were superior in the RT arm compared to nonRT arm (p: 0.043 and p &lt;0.001). In non-pancreatic periampullary cancer patients OS was 31 months in RT group and 51 months in non-RT group (p: 0.709). DFS was 29 months and 49.8 months respectively, p:0.504). Conclusions: The prognosis of PC was worse than non–pancreatic periampullary tumor. In PC adjuvant delayed RT improved patient outcome. Although OS and DFS were better in patients receiving CT alone, the difference was not statistically significant in non–pancreatic periampullary tumors.

Preoperative Imaging for Resectable Periampullary Cancer: Clinicopathologic Implications of Reported Radiographic Findings

BackgroundHigh-resolution, multiphase, computed tomography (CT) is a standard preoperative test prior to pancreatectomy, yet the clinical significance of routinely reported findings remains unknown. MethodsWe identified patients who underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over the previous 5 years and had a pancreas protocol CT at our institution. Clinicopathologic implications of reported CT findings were evaluated. ResultsThere were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs. No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size discrepancy of ≥1 cm between radiographic and pathologic tumor diameters was observed in 40 % of PAs, with CT underestimating the size in most instances (75 %). Radiographically enlarged lymph nodes were not associated with true lymph node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74 % lymph node negative, p = 0.5), but were associated with a preoperatively placed biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not associated with a vascular resection (3 % with CT vessel involvement vs 2 % without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %, respectively, p = 0.6). DiscussionWhile dedicated pancreas protocol CT provides unprecedented detail, the test may lead to overinterpretation of the extent of disease in some instances. A radiographic suggestion of enlarged lymph nodes and vascular involvement does not necessarily preclude exploration with curative intent. CTs with local disease should be reported in an objective template and carefully reviewed by a multidisciplinary group of surgeons, radiologists, and oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by resection.

Adjuvant Chemotherapy for Resected Periampullary Adenocarcinoma

To the Editor: Dr Neoptolemos and colleagues reported results from the large, multicenter European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary randomized controlled trial, which demonstrated no significant overall survival benefit from adjuvant chemotherapy in patients with nonpancreatic periampullary adenocarcinoma. We have 2 comments with regard to the trial data. We believe a central pathological review of the primary sites of origin should have been conducted to provide added clarity and further insight into the study. First, the determination of the primary site of origin (epicenter) of the resected periampullary cancers remains a challenge and is best conducted by a gastrointestinal pathologist. In the European Organization for Research and Treatment of Cancer (EORTC) phase 3 study of adjuvant radiotherapy in patients with pancreatic and periampullary carcinomas, central pathology review changed the diagnosis (pancreatic, periampullary, or unknown) in 5% of the cases. We believe the rate might be higher in this study because central pathology review would be required to solve the additional and more challenging problem of determining the specific sites of nonpancreatic periampullary adenocarcinoma (biliary, duodenal, or ampullary). In the ESPAC-3 study, 2 pancreatic pathologists reviewed each pathology report without reviewing histological slides. This has inherent limitations as demonstrated by the inability to properly classify the histological subtypes (pancreaticobiliary, intestinal, or mixed) of ampullary carcinoma in 162 patients (55%). Second, the low frequency of duodenal adenocarcinoma (2%) in this periampullary cohort contrasts with prior periampullary data sets in which duodenal adenocarcinoma was generally more common and represented 25% to 33% of nonpancreatic periampullary adenocarcinoma cases. We believe this reflects the degree of uncertainty with regard to the ascribed primary sites of periampullary adenocarcinoma. Because the site of nonpancreatic periampullary adenocarcinoma was a significant variable in the multivariate modeling, the uncertainty in determining the primary site of the periampullary adenocarcinoma in this study would limit the interpretation of the secondary multiple regression survival analysis. Could the authors also specify if the initiation of adjuvant therapy was restricted by a maximum time postsurgery and if a restaging imaging study was required prior to initiation of therapy?

Postoperative Radiotherapy in Periampullary Cancers: A Brief Review

The treatment of periampullary cancers is complex and challenging. Adjuvant therapy for resected periampullary and pancreatic cancers has been the subject of intense clinical investigations for several decades. Periampullary cancer management has often been clubbed with pancreatic cancers. Following surgery, adjuvant chemoradiotherapy has been widely accepted as standard of care in the USA, although different prospective and retrospective studies have shown conflicting results. Controversy regarding the effectiveness of chemoradiotherapy exists in the literature, both in terms of survival as well as toxicity. However, conventional postoperative radiotherapy practice needs to be reviewed in view of changes and developments in radiation techniques in the last decade. In this article, we review the management of periampullary cancers with special emphasis on the adjuvant postoperative radiotherapy.