Residual Pancreas Research Articles

Deep learning for auto-segmentation of the residual pancreas after pancreatic resection

Deep learning for auto-segmentation of the residual pancreas after pancreatic resection

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

Islet amyloid deposition and reduced β-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional β-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of β-cell area, α-cell area and amyloid deposits. Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

Incidence and risk factors of postoperative acute pancreatitis after pancreaticoduodenectomy: a systematic review and meta-analysis.

Postoperative acute pancreatitis (POAP) is a specific complication after pancreatectomy. The acute inflammatory response of the residual pancreas may affect the healing of pancreatoenteric anastomoses, leading to postoperative pancreatic fistulas (POPFs), abdominal infections, and even progressive systemic reactions, conditions that negatively affect patients' prognoses and can cause death. However, to the best of our knowledge, no systematic reviews or meta-analytic studies have assessed the incidence and risk factors of POAP after pancreaticoduodenectomy (PD). We searched PubMed, Web of Science, Embase, and Cochrane Library databases for relevant literature describing the outcomes of POAP after PD until November 25, 2022, and we used the Newcastle-Ottawa Scale to assess the quality of the studies. Next, we pooled the incidence of POAP and the odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors using a random-effect meta-analysis. I2 tests were used to assess heterogeneity between the studies. We analyzed data from 7,164 patients after PD from 23 articles that met the inclusion criteria for this study. The subgroup results of the meta-analysis by different POAP diagnostic criteria showed that the incidences of POAP were 15% (95% CI, 5-38) in the International Study Group for Pancreatic Surgery group, 51% (95% CI, 42-60) in the Connor group, 7% (95% CI, 2-24) in the Atlanta group, and 5% (95% CI, 2-14) in the unclear group. Being a woman [OR (1.37, 95% CI, 1.06-1.77)] or having a soft pancreatic texture [OR (2.56, 95% CI, 1.70-3.86)] were risk factors of POAP after PD. The results showed that POAP was common after PD, and its incidence varied widely according to different definitions. Large-scale reports are still needed, and surgeons should remain aware of this complication. identifier: CRD42022375124.

Diffuse Intraductal Papillary Mucinous Neoplasia in Both Native and Transplant Pancreases Despite Normal Residual Pancreas in the Respective First-Degree Donor.

Diffuse Intraductal Papillary Mucinous Neoplasia in Both Native and Transplant Pancreases Despite Normal Residual Pancreas in the Respective First-Degree Donor.

Carbon-Ion Radiotherapy for Local Recurrence Following Pancreatic Cancer Surgery

70% of patients able to receive surgical resection for pancreatic adenocarcinoma may ultimately experience recurrence; 25-35% have disease in the remnant pancreas or tumor bed. Surgical re-resection carries notable risks for morbidity, while success with photon irradiation has been limited. Carbon-ion radiotherapy (CIRT) has demonstrated unique promise in the treatment of locally advanced pancreatic cancer (LAPC). An initial cohort from 2011-2015 was published in 2017; here, we provide an update on CIRT safety and efficacy for post-surgical salvage of locally recurrent pancreatic cancer, with 60 cases from 2007 to 2020.Patients with locoregional recurrence following resection of pancreatic cancer were eligible. CIRT was conducted using 48.0 to 55.2 Gy (RBE) in 12 fractions, delivered over 3 weeks. Inclusion criteria included: 1) unresectable disease due to tumor invasion or patient refusal of re-resection; 2) absence of distant metastasis, 3) ECOG performance of 0 to 2. Patients with disease invading the GI tract, previous radiotherapy, or metallic stent placement were excluded.A total of 60 patients treated between January 2007 and 2020 were retrospectively reviewed. Median age was 65, with pancreatic head primary in 34 cases and body/tail in 26 cases. 34 cases underwent pancreaticoduodenectomy, with 26 distal pancreatectomies. 14 cases recurred in the residual pancreas, while 46 cases recurred in surrounding tissue. 16 cases received 48 - 52.8 Gy (RBE) via dose escalation, with 44 cases receiving 55.2 Gy (RBE). Grade 3 hematologic toxicity was seen in 3 cases, with no other G3+ acute or late toxicity was noted. 2-year local control was achieved in 56% for 48-52.8 Gy (RBE) and 61% for 55.2 Gy (RBE) cohorts. 2-year survival was 48% in the high dose cohort, with median survival time (MST) of 23 months.CIRT for postoperative recurrence of pancreatic cancer compared favorably to conventional chemoradiation salvage (2-year survival 38%, 16-month MST), with acceptable toxicity. CIRT may be a viable treatment alternative when re-resection is difficult.

S1499 Large Pancreatic Cyst in Von Hippel-Lindau (VHL) Syndrome Causing Bile Duct Obstruction

Introduction: Von Hippel-Lindau (VHL) syndrome is a rare autosomal inherited disorder characterized by the development of multiple tumors, the most common of which is renal cell carcinoma, hemangioblastomas, pheochromocytomas, and solid and cystic tumors of the pancreas. Morbidity and mortality in VHL are more commonly related to renal and central nervous system pathologies. Extrahepatic biliary obstruction secondary to pancreatic cysts is rare in patients with VHL. We present a case of extrahepatic biliary obstruction secondary to pancreatic cysts in a patient with a history of VHL syndrome successfully managed endoscopically. Case Description/Methods: 35-year-old woman with history of VHL and course complicated by clear cell renal cell carcinoma status post partial nephrectomy, cervical/medullary/fourth ventricle hemangioblastomas status post resection, and serous cystic pancreatic adenoma status post distal pancreatectomy and splenectomy with subsequent development of insulin-dependent diabetes mellitus type 2, presented with three days of right upper quadrant abdominal pain. MR Cholangiopancreatography revealed the residual pancreas was completely replaced by multiple cystic lesions with a dominant cyst in the head of the pancreas measuring 6.2 cm causing mass effect on the portal vein and mid to distal common bile duct with resultant intrahepatic, extrahepatic biliary ductal dilatation, and gallbladder distension. Using EUS with fine-needle biopsy of the cyst was done. Intraprocedural cholangiogram during ERCP revealed 14mm dilation of proximal extrahepatic biliary duct and non-opacification of the distal extrahepatic bile duct in the region of the pancreatic head, consistent with a stricture. CBD brushings were sent for cytology and a straight plastic biliary stent was successfully deployed across the stricture. After the endoscopic procedure, the patient demonstrated clinical improvement. Discussion: The pancreatic manifestation of VHL can present as a cystic, solid, or combined lesion. The management is complex because of the challenge in the differentiation of benign cystic lesions from malignant lesions. This case highlights the fact that pancreatic involvement leading to acute biliary obstruction, although uncommon, can occur in patients with VHL syndrome. Conservative management with endoscopic biliary stent placement and endoscopic surveillance (for secondary manifestations - portal hypertension) may be helpful in these patients, however eventual surgical management may be needed.Figure 1.: (Top left) Stricture/obstruction in ERCP, (Bottom left) EUS with biopsy, (Right) MRI showing cyst, CBD, and distended gallbladder.

Pyloruserhaltende partielle Pankreatoduodenektomie mit segmentaler Pfortaderresektion

Pylorus-preserving partial pancreatoduodenectomy is a complex visceral operation, especially when simultaneous resection and reconstruction of the portal venous axis is necessary. Pancreatic anastomosis plays a decisive role in this procedure, since postoperative pancreatic fistula (POPF) is a frequent complication, with serious consequences (morbidity and mortality) for the affected patient. Various techniques are available for anastomosing the residual pancreas: the duct-to-mucosa pancreaticojejunostomy, invaginating pancreatojejunostomy, Blumgart anastomosis and pancreatogastrostomy. Adenocarcinoma of the pancreatic head with portal vein infiltration. Pylorus-preserving pancreaticoduodenectomy (PPPD) with portal vein resection. A standardised and structured approach to pylorus-preserving partial pancreatoduodenectomy helps the surgeon to perform this procedure safely. Performing a simultaneous portal vein resection increases the complexity of the procedure, but nonetheless, if infiltration of the portal venous axis is suspected, the indication for en-bloc resection should be given generously, as intraoperatively it is not possible to differentiate reliably between inflammatory adherence and tumour infiltration and portal vein/V.-mesenterica-superior-resection does not increase morbidity and mortality. The choice of the surgical technique for anastomosing the residual pancreas should be made by the surgeon on the basis of his expertise and, if necessary, adapted to the patient's situs, since the most important pancreatic anastomosis techniques appear to be equivalent according to the current evidence.

Abstract 2185: Genetic analysis of metachronous pancreatic cancers

Abstract [Introduction] Early detection of pancreatic cancer is a key to curable surgery. However, many patients are diagnosed with an advanced disease and even in those who have an early stage tumor successfully resected, the development of metachronous cancer in the residual pancreas prevents a long-term survival. Thus, it is important to control metachronous tumors to improve clinical outcomes, whose pathogenesis, however, is poorly understood. In this study, we aimed to reveal the origin of metachronous tumors using an unbiased detection of somatic mutations in primary and metachronous tumors as well as adjacent precursor lesions. [Methods] Serially obtained formalin-fixed paraffin-embedded surgical specimens from 12 patients who had undergone curative surgery for an early-stage pancreatic cancer were subjected to laser microdissection for enrichment of tumor and precancerous components, from which DNA was extracted and analyzed for somatic mutations using whole-exome sequencing (WES) with matched normal DNA. Based on shared and private mutations across different samples, we interrogated history of clonal evolution of these lesions. [Results] Pathology for resected primary cancer was margin-negative in all patients. The median interval between the initial and second surgery was 34.6 months (12 - 65.1 months). Paired primary and metachronous cancers were analyzed in all 12 patients. An additional 5 pancreatic intraepithelial neoplasia (PanIN) samples were also analyzed in one case. We identified a median of 86 (range: 40-145) and 20 (14-42) somatic mutations using WES in cancers and PanIN lesions, respectively. None of the patients have known pathogenic germline variants. All samples had one or more driver mutations. In each patient, all driver mutations and many passenger mutations were shared between primary and metachronous cancer samples, suggesting that those metachronous tumors are evolutionally closely related to the primary cancer, despite long years before recurrence. Negative pathology of the margins at the initial surgery suggested that those metachronous lesions originated from distant dissemination or metastasis, rather than contiguous, intraductal invasion. By contrast, none of the mutations other than hotspot KRAS mutations were shared between precursor lesions and cancer samples. Despite multiple independent clones in the precancerous lesion, all metachronous tumors originated from the primary lesions in this study. [Conclusions] Our study suggests that even early pancreatic cancer might be disseminated within the pancreas and give rise to metachronous cancers, suggesting the importance of close monitoring of recurrence in the residual pancreas. Citation Format: Tomonori Hirano, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Tomomi Nishimura, Toshihiko Masui, Sachiko Minamiguhi, Hironori Haga, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Satoru Miyano, Uza Norimitsu, Yuzo Kodama, Hiroshi Seno, Seishi Ogawa. Genetic analysis of metachronous pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2185.

How to Perform Total Laparoscopic Duodenum-Preserving Pancreatic Head Resection Safely and Efficiently with Innovative Techniques.

Although rapid progress has been achieved in laparoscopic pancreaticoduodenectomy (PD) over the last decade, laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) remains a challenging surgery that has been rarely reported due to not only requiring complicated pancreaticojejunostomy (PJ) but also ensuring sufficient blood supplies to duodenum and common bile duct (CBD). We completed LDPPHR for 22 patients safely and efficiently with innovative techniques. Clinical outcomes, including rate of conversion to laparotomy, time of residual pancreatic duct reconstruction, incidence of postoperative complications, and time of hospital stay, were collected for 22 consecutive patients who underwent LDPPHR with innovative techniques as follows: application of indocyanine green (ICG) to visualize and preserve CBD and the vessels supplying the duodenum and CBD, Hong's PJ, and pancreatic duct end-to-end anastomosis (ETEA) for the residual pancreas. All surgeries were performed successfully under laparoscopy except for one case. The duration of ETEA was significantly shorter than PJ (18.2 ± 5.1min versus 27.5 ± 8.3min, p < 0.05). There was no significant difference in incidence of postoperative complications between the Hong's PJ and ETEA group. The overall incidence of postoperative pancreatic fistula (POPF) in the Hong's PJ and ETEA group was 23.5% and 20%, respectively, without grade C fistula. All complications were resolved after conservative treatment. By utilizing intraoperative ICG navigation, LDPPHR is a minimally invasive, safe, and efficient approach for chronic pancreatitis with pancreatic head stones by using pancreatic duct ETEA and benign or low-grade malignant tumors of the pancreatic head by using Hong's PJ.

Pancreatic Regeneration and Changes in Endocrine Function after Pancreatectomy

Background: Limited evidence is available on the regeneration of and functional changes to remnant pancreas after pancreatectomy. Therefore, we investigated the correlation between changes in volume and endocrine function in the remnant pancreas. Methods: Ninety patients undergoing pancreaticoduodenectomy (PD) and 45 undergoing distal pancreatectomy (DP) from January 2009 to December 2017 were included in this prospective study. Computed tomography was used to determine the volume of remnant pancreas 3 months, 1 year, and 2 years after pancreatectomy. Findings: The remnant pancreas volume compared to the initial residual pancreas was 80·79%, 68·67%, and 65·34% in the PD patients (p<0·001), and 106·25%, 106·62%, and 110·43% (p=0·019) in the DP patients at 3 months, 1 year, and 2 years, respectively. The DP patients had a higher incidence of new-onset diabetes than PD patients (33·3% vs. 22·7%). In addition, PD patients had more pancreatic duct dilatation with severe atrophy of the remnant pancreas (p=0·027), whereas DP patients had better pancreas regeneration (p=0·084) with spleen preservation. The changes in pancreas volume did not correlate with postoperative new-onset diabetes. Interestingly, the PD group had significantly greater restoration of endocrine function based on secretion of C-peptide. Interpretation: Pancreatic regeneration is more predominant after DP than PD. The distal portion of the pancreas had greater restoration capacity, corresponding with a lower rate of new-onset diabetes. Funding Statement: The study was supported by Taiwan Ministry of Science and Technology (MOST108-2321-B-006-014), Ministry of Health and Welfare (MOHW 107-TDU-B-212-114026A), and HSU-YUAN Education Foundation (HY-2018-001). Declaration of Interests: The authors reported no conflict of interest. Ethics Approval Statement: IRB approved by the Institutional Review Board of the National Cheng Kung University Hospital (approval number of B-ER-108-312).

Abstract 5877: Genetic analysis of metachronous pancreatic cancers

Abstract [Introduction] Early detection of pancreatic cancer is a key to curable surgery. However, many patients are diagnosed in an advanced stage and even in those cases who had a surgical resection of early stage tumors, metachronous pancreatic cancer in residual pancreas prevents cure. Thus, it is important to control metachronous tumors to improve clinical outcomes, whose pathogenesis is poorly understood. In this study, we aimed to reveal the origin of metachronous pancreatic cancers using an unbiased detection of somatic mutations in primary and metachronous cancers as well as adjacent precursor lesions. [Methods] Serially obtained formalin-fixed paraffin-embedded surgical specimens from 8 patient who had undergone curative surgery for an early stage pancreatic cancer were subjected to laser microdissection for the enrichment of tumor and PanIN lesions, from which DNA was extracted and analyzed for somatic mutations of each lesion by whole-exome sequencing (WES) with matched normal DNA. Based on shared and private mutations across different samples, we interrogated history of clonal evolution of these lesions. [Results] Pathology for primary cancer were margin-negative in all patients. The median interval between the initial and second surgery was 29.8 months (23 - 64.4 months). We analyzed a median of two cancer and one PanIN samples (0-5), from which we identified a median number of 45(range: 26-69) and 20 (14-42) somatic mutations using WES, respectively. None of the patients have known pathogenic germline variants. All samples had one or more driver mutations. In each patient, all driver mutations and more than half of passenger mutations were shared between primary and metachronous cancer samples, suggesting that those metachronous tumors are evolutionally closely related to the primary cancer. Negative pathology of the margins at the initial surgery suggested that those metachronous lesions originated from distant dissemination or metastasis, rather than contiguous, intraductal invasion. By contrast, none of the mutations other than hotspot KRAS mutations were shared between precursor lesions and cancer samples. Despite multiple independent clones in the precancerous lesion, all metachronous tumors originated from the primary lesions in this study. [Conclusions] Our study suggests that even early pancreatic cancer might be disseminated within the pancreas and contribute to metachronous cancers, suggesting the importance of close monitoring of the recurrence in the residual pancreas. Citation Format: Hirano Tomonori, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Yoshikage Inoue, Tomomi Nishimura, Yoichi Fujii, Akira Yokoyama, Hideki Makishima, Toshihiko Masui, Shinji Uemoto, Sachiko Minamiguchi, Hironori Haga, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Satoru Miyano, Norimitsu Uza, Yuzo Kodama, Hiroshi Seno, Seishi Ogawa. Genetic analysis of metachronous pancreatic cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5877.

The relationship between cholecystokinin secretion and pancreatic [11C]methionine uptake in patients after partial pancreaticoduodenectomy.

The pancreatic uptake of [11C]methionine ([11C]MET) is associated with beta-cell function and insulin secretion, but [11C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [11C]MET in the residual pancreas following pancreaticoduodenectomy. Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56-67years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8-26years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180min after ingestion. Simultaneously, 800MBq of [11C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60min after injection. Integrated CCK (AUC30) correlated with SUVmax (AUC60, R2 = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC60) and CCK concentrations and young age as significant independent predictors of [11C] methionine uptake. The association between CCK concentrations and pancreatic [11C]MET uptake might indicate a causal relationship. Further research should assess whether [11C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity.

A Case of Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Adenosquamous Cell Carcinoma in Residual Pancreas Five Years after Surgery for Intraductal Papillary Mucinous Adenocarcinoma

A Case of Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Adenosquamous Cell Carcinoma in Residual Pancreas Five Years after Surgery for Intraductal Papillary Mucinous Adenocarcinoma

Abstract 5126: Genetic analysis of metachronous pancreatic cancers

Abstract [Introduction] Early detection of pancreatic cancer is a key to curable surgery, although many are diagnosed in advanced stage. However, even in those cases in which cancer was detected early enough for curative resection, metachronous pancreatic cancer may occur in residual pancreas, whose pathogenesis, including its relationship with primary cancer, has been poorly understood. In this study, we aimed to reveal the origin of metachronous pancreatic cancers using an unbiased detection of somatic mutations in primary and metachronous cancers as well as adjacent precursor lesions. [Methods] Samples were obtained from longitudinal sampling from above lesions using laser microdissection from formalin-fixed paraffin-embedded surgical specimens. DNA was extracted and analyzed for somatic mutations of each lesion by whole-exome sequencing with matched normal DNA. On the basis of shared and private mutations across different samples, we interrogated history of clonal evolution of these lesions. [Results] Four patients were enrolled who underwent curative surgery for early pancreatic cancer and subsequently for metachronous tumors in the residual pancreas. Pathology from surgery for primary cancer were margin-negative in all patients. The median interval between the initial and second surgery was 29.8 months (22.8 - 38.3 months). The number of precursor lesions analyzed was from 0 to 5 per patient. The median number of somatic mutations per sample was 78 (range: 41-92) in cancers and 20 (14-42) in precursor lesions. None of the patients have known pathogenic germline mutations. With a median of 78 and 20 mutations per sample, all samples had one or more driver mutations. In each case, all driver mutations that were detected in cancers were shared between primary and metachronous cancer. It indicated that metachronous cancer branched off from primary cancers at later stage of carcinogenesis. And negative margin at initial surgery suggested that metachronous cancer was formed by dissemination or metastasizing rather than Intraductal progression. By contrast, none of the mutations other than a hotspot KRAS mutations were shared between precursor lesions and cancers, suggesting multiple independent clonal growth of precancerous cells in the cancer bearing pancreas. [Conclusions] Our study shows that metachronous pancreatic cancers are derived from the same origin of initial cancer. Therefore, even in the case of early pancreatic cancer careful checkup for recurrence in the residual pancreas is important. Citation Format: Hirano Tomonori, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Yoshikage Inoue, Tomomi Nishimura, Yoichi Fujii, Akira Yokoyama, Hideki Makishima, Toshihiko Masui, Shinji Uemoto, Sachiko Minamiguchi, Hironori Haga, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Satoru Miyano, Norimitsu Uza, Yuzo Kodama, Hiroshi Seno, Tsutomu Chiba, Seishi Ogawa. Genetic analysis of metachronous pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5126.

Mixed ductal-acinar cell carcinoma of the pancreas: A case report.

Mixed carcinoma of the pancreas is defined as the concurrent existence of pancreatic ductal carcinoma, acinar cell carcinoma, and/or islet cell carcinoma within the same neoplasm. We herein report a rare case of mixed ductal-acinar cell carcinoma in a 74-year-old man who was undergoing treatment for hypertension and diabetes at another hospital. After an abrupt worsening of his blood glucose control, the patient was referred to our hospital for further evaluation. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging revealed a tumor with a multilocular cystic lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed obstruction of the main pancreatic duct and dilation of the dorsal pancreatic duct; in addition, adenocarcinoma was detected in the pancreatic juice cytology. Based on the abovementioned findings, the patient was diagnosed with carcinoma of the pancreatic head and underwent subtotal stomach-preserving pancreaticoduodenectomy. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with mixed ductal-acinar cell carcinoma. The patient was prescribed TS-1 as postoperative adjuvant chemotherapy upon discharge. However, treatment was discontinued 2 months later due to marked general malaise, and the patient succumbed to tumor recurrence in the residual pancreas 12 months after the surgery.

Subtype of intraductal papillary mucinous neoplasm of the pancreas is important to the development of metachronous high-risk lesions after pancreatectomy.

Backgrounds/AimsAlthough intraductal papillary mucinous neoplasm (IPMN) has showed a favorable prognosis compared to pancreatic ductal adenocarcinoma, its recurrence patterns have somewhat questionable in detail. After partial pancreatectomy for IPMN, the evaluation for risk of metachronous occurrence of high-risk lesions (HRL) in the residual pancreas is important to establish a postoperative surveillance modality and duration of follow-up. This study aimed to evaluate the factors that may predict the metachronous occurrence of HRL in the remnant pancreas after surgery of the IPMN.MethodsFrom 2005 to 2016, clinicopathologic and surveillance data for 346 consecutive patients who underwent surgical resection for IPMN were reviewed retrospectively. Histologic subtype was classified as gastric, intestinal, pancreato-biliary, or oncocytic type.ResultsAll of IPMN were classified as main duct (n=64, 18.5%), branch duct (n=171, 49.4%), and mixed type (n=111, 32.1%). Forty-eight patients (13.9%) experienced recurrence during follow-up. Among these, 9 patients (2.6%) were identified to metachronous development of HRL in the remnant pancreas. After multivariate analysis, high-grade dysplasia (HGD) or invasive carcinoma (IC) compared to low- or intermediate dysplasia was only independent risk factor for recurrence (HR 3.688, 95% CI 2.124– 12.524, p=0.009). The independent risk factors for metachronous development were HGD/IC (HR 8.414, 95% CI 4.310– 16.426, p=0.001), and intestinal/pancreato-biliary subtype compared to gastric subtype (HR 7.874, 95% CI 3.650– 27.027, p=0.010).ConclusionsPatients with high-grade dysplasia or invasive carcinoma, and with intestinal or pancreatobiliary subtype should undergo close, long-term surveillance of the remnant pancreas after initial resection.

Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study

Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content<200μg per gram of feces while EndoPI was defined as fasting glucose>126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; P<0.001), while the rate of EndoPI was lower after PD vs. LP, but this difference did not reach statistical significance (28% vs. 38.5%; P=0.412). There was no statistically significant difference in ExoPI found between pancreatico-gastrostomy (PG) and pancreatico-jejunostomy (PJ) (100% vs. 98%; P=1.000). Remnant pancreatic volume less than 39.5% was predictive of ExoPI. ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP.

Agenesis of the dorsal pancreas: systematic review of a clinical challenge.

Agenesis of the dorsal pancreas is a rare malformation. Since 1911 and until 2008, 53 cases have been reported. Several authors have recently described the association of this anomaly with neoplasia of the ventral pancreas, thus we performed a systematic review of the literature from 2008 to 2015. A systematic review of the MedLine and ISI Web of Science Databases from 2008 until 2015 was carried out, and 30 articles which met the inclusion criteria were identified that included a total of 53 patients: 7 children and 46 adults. Although dorsal pancreatic agenesis is a rare malformation, given its association with non-alcoholic pancreatitis and neoplasia of the residual pancreas, physicians should maintain an expectant attitude.

Pancreatic exocrine insufficiency following pancreatic resection.

Untreated pancreatic exocrine dysfunction is associated with poor quality of life and reduced survival, but is difficult to diagnose following pancreatic resection. Many factors including the extent of the surgery, the health of the residual pancreas and the type of reconstruction must be considered. Patients remain undertreated, and consequently there is much debate to whether or not pancreatic enzyme replacement therapy should be routinely prescribed following pancreatic resection. A review of the literature was undertaken to establish the incidence of PEI and factors identifying treatment. Forty two to forty five percent of patients undergoing pancreatico-duodenectomy (PD) experience pancreatic exocrine insufficiency pre-operatively, whilst the post-operative incidence is 56-98% in PD, and 12-80% following distal and central pancreatectomy. Routine use of pancreatic enzyme replacement should be considered at a starting dose of 50 to 75,000units lipase with meals and 25,000 to 50,000units with snacks in this patient group. Patients who have had a central or distal pancreatectomy should be individually assessed for pancreatic exocrine insufficiency in the post operative period, with those undergoing extensive resection most likely to experience insufficiency. Patients who fail to respond to pancreatic enzyme replacement therapy should be referred to a specialist dietitian, be advised on dose adjustment, and undergo investigation to exclude other gastro-intestinal pathology, including small bowel bacterial overgrowth and bile acid malabsorption.

Very small embryonic-like stem cells are involved in regeneration of mouse pancreas post-pancreatectomy.

IntroductionDespite numerous research efforts, mechanisms underlying regeneration of pancreas remains controversial. Views are divided whether stem cells are involved during pancreatic regeneration or it involves duplication of pre-existing islets or ductal cells or whether pancreatic islet numbers are fixed by birth or they renew throughout life. Pluripotent embryonic stem (ES) and induced pluripotent stem (iPS) cells have been used by several groups to regenerate diabetic mouse pancreas but the beneficial effects are short-lived. It has been suggested that cells obtained after directed differentiation of ES/iPS cells resemble fetal and not their adult counterparts; thus are functionally different and may be of little use to regenerate adult pancreas. A novel population of pluripotent very small embryonic-like stem cells (VSELs) exists in several adult body tissues in both mice and humans. VSELs have been reported in the mouse pancreas, and nuclear octamer-binding transcription factor 4 (OCT-4) positive, small-sized cells have also been detected in human pancreas. VSELs are mobilized into peripheral blood in streptozotocin treated diabetic mice and also in patients with pancreatic cancer. This study aimed to evaluate whether VSELs are involved during regeneration of adult mouse pancreas after partial pancreatectomy.MethodsMice were subjected to partial pancreatectomy wherein almost 70% of pancreas was surgically removed and residual pancreas was studied on Days 1, 3 and 5 post-surgery.ResultsVSELs were detected in Hematoxylin and Eosin stained smears of pancreatic tissue as spherical, small sized cells with a large nucleus surrounded by a thin rim of cytoplasm and could be sorted as LIN-/CD45-/SCA-1+ cells by flow cytometry. Results reveal that although neutrophils with multi-lobed nuclei are mobilized into the pancreas on day 1 after pancreatectomy, by day 5 VSELs with spherical nuclei, high nucleo-cytoplasmic ratio and nuclear OCT-4 are mobilized into the residual pancreas. VSELs undergo differentiation and give rise to PDX-1 and OCT-4 positive progenitors which possibly regenerate both acinar cells and islets.ConclusionsResults provide direct evidence supporting the presence of VSELs in adult mouse pancreas and their role during regeneration. VSELs are an interesting alternative to ES/iPS cells to regenerate a diabetic pancreas in future.