Resection For Periampullary Cancer Research Articles

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

The five periampullary cancers: Not just different siblings but different families—An international multicenter cohort study.

4167 Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC) and ampullary adenocarcinoma (AAC). Based on histopathology, the AAC is currently subdivided in the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype. Despite close anatomical resemblance, it is unclear how the ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This is an international multicenter cohort study, including patients after curative intent resection for periampullary cancer retrieved from 45 centers (from Europe, USA, Asia and Canada) between 2010 and 2021. Pre-operative CA19-9, differences in pathology and postoperative pancreatic fistula (POPF, grade B/C), 8-year overall survival (OS) and disease-free interval (DFI) were compared between DAC, AmpIT, AmpPB, dCCA and PDAC. Results: Overall, 3809 patients were included of which 348 DAC, 774 AmpIT, 848 AmpPB, 1036 dCCA and 803 PDAC. The best 8-years overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, p&lt;0.001), dCCA (26.4%, p=0.020) and last, PDAC (12.9%, P&lt;0.001). The best 8-years DFI was measured for AmpIT (62.7%) and the worst for both dCCA and PDAC (24.9% and 21.8%). This pattern correlated with the height of the pre-operative CA19-9 but not with the pathology, in which the largest and most progressed tumors were found in DAC. The incidence of POPF was lower in the pancreas-related tumor types (AmpPB 18.5%, PDAC 8.3%) compared to the non-pancreas related types (DAC 27.3%, AmpIT 25.5%, dCCA 27.6%). Conclusions: Despite the close anatomic relation of the five periampullary cancers, this study shows that there are prognostic and clinically relevant differences in terms of preoperative blood markers, pathology, complications, long-term survival, and recurrence. More characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers”, this study emphasizes the need for individual evaluation of each histopathological periampullary subtype with the ampullary subtypes as individual entities in future studies.

Factors influencing local and distant recurrence following resection of periampullary cancer

Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P < 0.001). Tumour subtype (distal common bile duct (CBD): odds ratio (OR) 6.18, 95 per cent c.i. 2.19 to 17.46) and node-positive status (OR 2.36, 1.26 to 4.43) were independently associated with higher rates of LR. The most common site for isolated LR was along the superior mesenteric artery (12 of 23 patients). Tumour subtype (distal CBD: OR 2.86, 1.09 to 7.52), nodal positivity (OR 2.46, 1.53 to 3.94), and presence of perineural invasion (OR 1.80, 1.02 to 3.18) were independently associated with DM. Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Impact of Postoperative Skeletal Muscle Change on Survival After Resection of Periampullary Cancer

Impact of Postoperative Skeletal Muscle Change on Survival After Resection of Periampullary Cancer

Fractional uptake of circulating tumor cells into liver-lung compartments during curative resection of periampullary cancer.

Circulating tumor cells (CTCs) are able to predict outcome in patients with breast, colon and prostate cancer and appear to be promising biomarkers of pancreatic carcinoma. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTCs during curative resection of periampullary cancer. A commercially available instrument (IsofluxR) was used to quantify blood content of CTC in 10 patients with periampullary cancer according to preoperative diagnostics. Portal and arterial blood samples (~8 ml each) were simultaneously collected intra-operatively following surgical dissection prior to division of the pancreas for tumor removal. Quantitative CTC analyses were performed according to standardized protocols for immune-magnetic enrichment of CTC. Flow cytometry was applied for qualitative evaluations of various CTC markers in 7 patients. There was a statistically significant difference in the number of CTCs collected in the portal blood [58±14 cells per 100 ml; mean ± standard error (SE)] vs. arterial blood [24±7 cells per 100 ml (SE), P<0.025]. A fractional uptake of ≥40% across liver and lung compartments of assumed malignant CTC was estimated to correspond to the appearance of ~410 tumor cells per minute during pancreatic resections based on estimated hepatic blood flow, measured tumor cell mass and tumor cell proliferation activity. Complications in the collection of portal blood were not observed. A significant uptake across liver or lung compartments of potentially malignant tumor CTCs from periampullary carcinoma may represent a model to capture, define and characterize cell clones with metastatic potential in liver and lung tissues following surgical resection.

Pancreaticoduodenectomy for periampullary cancer: does the tumour entity influence perioperative morbidity and long-term outcome?

Background: Malignant tumours of the periampullary region include ductal adenocarcinoma of the pancreas (Pan-Ca), distal bile duct cancer (DBDC) and adenocarcinoma of the ampulla (Amp-Ca). The present retrospective clinical study was designed to evaluate the influence of tumour entity on postoperative complications and identify risk factors predicting survival and morbidity.Methods: We retrospectively analysed data from all patients who underwent pancreatic resection for periampullary cancer with curative intent (R0 or R1). Demographic data, risk factors, perioperative complications and survival rates for the different subtypes were assessed.Results: A total of 225 patients with periampullary cancer were identified: 124 (55.1%) had Pan-Ca, 55 (24.4%) had DBDC and 46 had (20.4%) Amp-Ca. Sixty-nine patients (30.7%) had major complications (grade IIIb–V). Patients with DBDC had significantly more grade C pancreatic fistulas. Univariate analysis revealed male gender, BMI >30, R1-status, and low-grade tumour differentiation as risk factors for major complications. Overall in-hospital-mortality was 6.7%.Conclusions: Further research will be needed to implement more individualized therapy.

Underutilization of Surgery in Periampullary Cancer Treatment

BackgroundSite-specific outcomes of resection for periampullary cancer have not been analyzed on a large, registry-based scale. MethodsWe assessed data on periampullary cancers from the SEER database. Site- and stage-specific outcomes were analyzed. Resection was compared to no resection. ResultsResection was the main therapy in stages 1 and 2 (resection vs. no resection, 8644 vs. 7208 patients), was less frequent in stage 3 (1248 vs. 2783 patients) and was rarely—but still—used in stage 4 disease (541 vs. 11,212 patients). Pancreatic head (75.7%), 11.4% distal bile duct, 7.7% ampullary, and 5.3% duodenal cancers. Cancer subtype-independent median survival was 22.0 (resection) vs. 7.0 months (no resection) in stages 1 and 2, 21.0 vs. 8.0 months in stage 3, and 10.0 vs. 3.0 months in stage 4. Subtype-dependent median survival (resection vs. no resection) was 18.0 vs. 5.0 months in pancreatic head, 19.0 vs 4.0 months in distal bile duct, 41.0 vs 7.0 months in ampullary, and 38.0 vs 4.0 months in duodenal adenocarcinoma. On multivariable analysis, patient comorbidities, marital and insurance status, and income all influenced the decision to undergo resection. ConclusionsSurgery is still underutilized in the treatment of periampullary cancers. Patients with cancers originating from the duodenum or the ampulla of Vater benefit most from resectional surgery.

AB014. S014. Fractional uptake of circulating tumor cells across liver-lung compartments during resections of periampullary cancer aimed at cure

Background: Circulating tumor cells (CTCs) are prognostic for outcome in breast, colon, and prostate cancer and seem to represent promising biomarkers of pancreatic carcinoma as well. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTC during resection of periampullary cancer aimed at cure in a limited number of patients.

Systematic evaluation of radiological findings in the assessment of resectability of peri-ampullary cancer by CT using different contrast phase protocols

To determine the relative significance of radiological signs in determining the resectability of peri-ampullary cancer (PC) and to assess the value of multi-phase imaging in detecting these findings. Blinded, double re-reporting of preoperative imaging from five hospitals was undertaken of 411 patients undergoing surgery for PC over an 8-year period, of whom 119 patients were found to be inoperable at the time of surgery. The median tumour size was 26.7mm and the proportion of patients reported to have regional lymphadenopathy (RL), venous (VI) and arterial involvement (AI) was 24.7%, 11.5%, and 3.9%, respectively and was similar regardless of the number of contrast phases undertaken. Significant associations were, however, noted between individual risk factors: VI was closely associated with tumour size (p=0.002) and AI (p<0.0001). In multivariate analysis AI, VI, and RL were independently associated with resectability (relative risk of resection=0.05, 0.31, and 0.51, respectively). Tumour size, however, was not associated with resectability when VI was included in the multivariate model. The use of multiple vascular contrast phases has no measureable impact on the rate of determination of tumour resectability of PC. In preoperative staging, AI is the most significant adverse finding for resectability. Large tumour diameter is not an adverse finding in isolation from other risk factors.

Skeletal muscle attenuation, but not skeletal muscle mass, is associated with worse survival and major complications following resection of periampullary cancer

Skeletal muscle attenuation, but not skeletal muscle mass, is associated with worse survival and major complications following resection of periampullary cancer

Resection of isolated local and metastatic recurrence in periampullary adenocarcinoma

BackgroundThe majority of patients with periampullary cancer develop local or metastatic recurrence despite successful negative margin resection. Unfortunately, there are no established therapeutic strategies for managing these patients. The literature on the surgical resection of recurrent disease is limited. MethodsThis is a retrospective study evaluating patients who underwent reoperative resection of recurrent periampullary cancer at a single institution between 1990 and 2011. Perioperative outcomes were compared with those of the original primary resections for patients with local recurrence. Kaplan–Meier curves were used to evaluate survival. ResultsTwenty-two patients underwent reoperative resection following the successful primary resection of periampullary cancers. Median survival from the time of reoperation was 28.1 months. A greater survival benefit was seen in patients undergoing reoperative resection with >15 months between the primary resection and recurrence (40.6 months versus 8.2 months; P < 0.05). Complication rates were lower after reoperative resection compared with the primary resection (20% versus 70%). Perioperative characteristics including operative time, estimated blood loss and hospital stay were similar in both the primary and reoperation procedures. ConclusionsSurgical resection of periampullary cancer recurrence is feasible, safe and may offer survival benefits in comparison with alternative treatment modalities. Reoperative resection should be considered, especially in patients in whom the time to recurrence is lengthy.

Residual Tumor After Pancreaticoduodenectomy: The Impact of a Brand New Standardized Technique to Evaluate Resection Margin Status

Context Pancreaticoduodenectomy (PD) is the only potentially curative treatment for patients affected by periampullary cancer. Resection margin involvement (R1) after PD ranges from 14% to 75% and it has been demonstrated to significantly affect survival. It has been recently supposed that the reason of this difference is the lack of consensus on the method used to manage the specimen. The results of recent studies indicate that the use of a new technique to manage the specimen determines a significant increase of R1 resection rate up to 75%. We report the results of a case control study that evaluated the impact of this new technique in a series of 50 patients undergoing PD for cancer. Material and Methods From October 2004 through October 2010 at our institution surgical specimens after PD were analyzed by the pathologist according to international approved guidelines [1]. From November 2010 this method was replaced by a different technique [2] that included: 1) introduction of the concept of “circumferential margins”; 2) multicolor inking of six margins (a. Pancreatic transection margin; b. Biliary transection margin; c. Anterior surface of the pancreatic head; d. Posterior surface of the pancreatic head; e. Bed of the superior mesenteric vein; f. Bed of the superior mesenteric artery); 3) axial slicing of the specimen; 4) the following definition of R0 resection: tumor at a distance of at least 1 mm from the margin. From November 2010 through November 2011 we utilized the new method to manage 50 consecutive specimens after PD. In order to analyze the results of the new method we planned a case control study focusing the following parameters: 1) rate of R1 resections; 2) average number of examined blocks; 3) average number of examined lymph nodes; 4) lymph nodal status. Results Statistical analysis of the two groups of patients showed no significant epidemiological, pathological and clinical difference. 1) The rate of R1 resections was: 68% (new method) and 10% (control group) (P<0.0001); 2) the average number of examined blocks was 48.2 (range: 29-92) (new method) and 10.7 (range: 5-21) (control group) (P<0.005); 3) the mean number of examined lymph nodes was 33.2 (range: 11-60) (new method) and 8.7 (range: 0-26) (control group) (P<0.005); 4) metastatic lymph nodes were found in 90% (new method) and in 46% (control group) (P<0.001). Discussion Our results confirmed that the new method determines a statistically significant increase of R1 resections if compared with the conventional method. This evidence confirms recently published data showing that “conventional technique” underestimate the rate of R1 resections. As a consequence, we can assume that R0 resection for periampullary cancer is performed only in a minority of cases. If confirmed, this evidence will impact clinical management of pancreatic cancer.

Lymph node ratio predicts local recurrence for periampullary tumours

To better define the prognostic role of nodal disease, evaluation of metastatic lymph node ratio (MLR) has been performed, and this method has recently gained prominence in various gastrointestinal cancers. The present study attempts to identify prognostic factors and evaluate the independent prognostic influence of MLR in patients who have undergone curative pancreaticoduodenectomy. In our institution within the study period, 111 patients received curative pancreaticoduodenectomy for periampullary cancers. Clinicopathologic data were collected and MLR was calculated for each of the patients. Patients were then divided into four groups based on MLR value: MLR 1 = 0; MLR 2 = 0.01-0.2; MLR 3 0.21-0.4; and MLR 4 >0.4. Increasing MLR correlates with high recurrence rate and lower overall survival (OS) with significance (P < 0.001, P < 0.001). The recurrent group showed significantly lower OS than the non-recurrent group (P < 0.001). In the multivariate analysis for recurrence, MLR was identified as the only independent prognostic factor (P < 0.001). The simple and easily obtainable MLR is well qualified as a prognostic factor in patients who undergo curatively radical resection for periampullary cancer. Furthermore, MLR can overcome the limitations of evaluation of lymph nodes status, allowing it to be used as a potential prognostic factor.

Predicting resectability of periampullary cancer with three-dimensional computed tomography.

The radiographic assessment of extent of tumor burden and local vascular invasion appears to be enhanced with three-dimensional computed tomography (3D-CT). The purpose of this study was to evaluate the impact of preoperative 3D-CT in determining the resectability of patients with periampullary tumors. Intraoperative findings from exploratory laparotomy were gathered prospectively from 140 patients who were thought to have periampullary tumors and were deemed resectable after undergoing preoperative 3D-CT imaging. CT findings were compared to intraoperative findings, and the accuracy of 3D-CT in predicting tumor resectability and, ultimately, the likelihood of obtaining a margin-negative resection were assessed. Of the 140 patients who were thought to have resectable periampullary tumors after preoperative 3D-CT, 115 (82%) were subsequently determined to have periampullary cancer. The remaining 25 patients had benign disease. Among the patients with periampullary cancer, the extent of local tumor burden involving the pancreas and peripancreatic tissues was accurately depicted by 3D-CT in 93% of the patients. 3D-CT was 95% accurate in determining cancer invasion of the superior mesenteric vessels. Preoperative 3D-CT accurately predicted periampullary cancer resectability and a margin-negative resection in 98% and 86% of patients, respectively. For patients with pancreatic adenocarcinoma (n=85), preoperative 3D-CT resulted in a resectability rate and a margin-negative resection rate of 79% and 73%, respectively. The ability of 3D-CT to predict a margin-negative resection for periampullary cancer, including pancreatic adenocarcinoma, relies on its enhanced assessment of the extent of local tumor burden and involvement of the mesenteric vascular anatomy.

Subtotal pancreatoduodenectomy: use of a defunctionalized loop for pancreatic stump drainage.

Since its introduction, pancreaticoduodenal resection for periampullary cancer has undergone numerous modifications. As a result, there has been a dramatic decline in the mortality rate. However, a high morbidity rate, mainly due to pancreatic fistula formation, is still reported. To evaluate the results of the use of a defunctionalized jejunal loop in patients undergoing pancreatoduodenectomy to minimize both the frequency and severity of anastomotic leak. Second Surgical Department, Athens University, Aretaieon Hospital, Athens, Greece. A series of retrospective cases from February 1990 to December 1997. One hundred five patients who underwent pancreatoduodenectomy and had the pancreatic stump drained in a defunctionalized jejunal loop. To avoid problems related to fistula formation due to erosion of the anastomoses from activated pancreatic enzymes, a defunctionalized jejunal loop was constructed and the pancreatic stump was invaginated into the end of this loop. Using the defunctionalized jejunal loop, the mean (+/-SD) hospitalization was 7.57+/-1.42 days, the morbidity rate was 11.2%, and the mortality rate was 0.95%. A modification of pancreatoduodenectomy for the treatment of pancreatic cancer resulted in an improvement in the immediate results of subtotal pancreatoduodenectomy. Careful detachment of the posterior surface of the pancreas from the anterior surface of the portal vein and performance of pancreaticojejunal anastomosis to a defunctionalized jejunal loop results in lower mortality and morbidity rates, thus making pancreatoduodenectomy a safe procedure.