Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Lymph node involvement is rare in mucinous cystic neoplasms of the pancreas: Role of minimally invasive surgery.

Mucinous cystic neoplasm (MCN) is a premalignant cystic tumor of the pancreas. Resection of MCN in the distal pancreas is a standard treatment; however, at present, there is no consensus on the necessity or extent of lymph node dissection, and minimally invasive pancreatectomy is commonly the preferred surgical technique. Thus, the present study aimed to assess the efficacy of minimally invasive surgery and the extent of lymph node metastasis as factors in determining an appropriate surgical treatment for MCN. The present study retrospectively analyzed 21 consecutive patients who underwent distal pancreatectomy (DP) for MCN under general anesthesia at Chiba University Hospital (Chiba, Japan) between April 2011 and July 2019. All 21 patients were female. DP with a splenectomy was performed in all the patients. A total of 14 patients underwent laparoscopic DP (LDP). No lymph node metastasis was found in any of the patients. The minimally invasive surgery group had lower operative blood loss and a shorter hospital stay than the open surgery group. There was no significant difference in the number of dissected lymph nodes between the open surgery group and the minimally invasive surgery group. Preoperative findings of malignancy in MCN included solid components on enhanced CT and endoscopic ultrasonography, high carbohydrate antigen 19-9 values and large tumor size. In conclusion, DP with spleen preservation, which is minimally invasive, may be preferentially considered as a surgical technique for MCN without malignant findings because lymph node metastases are rare in MCN and were not observed in the present study.

FGFR2 maintains cancer cell differentiation via AKT signaling in esophageal squamous cell carcinoma.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important for signaling to maintain cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). However, which FGF receptor, 1, 2, 3, 4, and L1, is essential or whether FGFRs have distinct different roles in ESCC-CSCs is still in question. This study shows that FGFR2, particularly the IIIb isoform, is highly expressed in non-CSCs. Non-CSCs have an epithelial phenotype, and such cells are more differentiated in ESCC. Further, FGFR2 induces keratinocyte differentiation through AKT but not MAPK signaling and diminishes CSC populations. Conversely, knockdown of FGFR2 induces epithelial-mesenchymal transition (EMT) and enriches CSC populations in ESCC. Finally, data analysis using The Cancer Genome Atlas (TCGA) dataset shows that expression of FGFR2 significantly correlated with cancer cell differentiation in clinical ESCC samples. The present study shows that each FGFR has a distinct role and FGFR2-AKT signaling is a key driver of keratinocyte differentiation in ESCC. Activation of FGFR2-AKT signaling could be a future therapeutic option targeting CSC in ESCC.

Complement factor B regulates cellular senescence and is associated with poor prognosis in pancreatic cancer.

BACKGROUND: The interplay between cancer cells and stromal components, including soluble mediators released from cancer cells, contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). Here, we set out to identify key secreted proteins involved in PDAC progression. METHODS: We performed secretome analyses of culture media of mouse pancreatic intraepithelial neoplasia (PanIN) and PDAC cells using Stable Isotope Labeling by Amino acid in Cell culture (SILAC) with click chemistry and liquid chromatography-mass spectrometry (LC-MS/MS). The results obtained were verified in primary PDAC tissue samples and cell line models. RESULTS: Complement factor B (CFB) was identified as one of the robustly upregulated proteins, and found to exhibit elevated expression in PDAC cells compared to PanIN cells. Endogenous CFB knockdown by a specific siRNA dramatically decreased the proliferation of PDAC cells, PANC-1 and MIA PaCa-II. CFB knockdown induced increases in the number of senescence-associated-ß-galactosidase (SA-ß-gal) positive cells exhibiting p21 expression upregulation, which promotes cellular senescence with cyclinD1 accumulation. Furthermore, CFB knockdown facilitated downregulation of proliferating cell nuclear antigen and led to cell cycle arrest in the G1 phase in PDAC cells. Using immunohistochemistry, we found that high stromal CFB expression was associated with unfavorable clinical outcomes with hematogenous dissemination after surgery in human PDAC patients. Despite the presence of enriched CD8+ tumor infiltrating lymphocytes in the PDAC tumor microenvironments, patients with a high stromal CFB expression exhibited a significantly poorer prognosis compared to those with a low stromal CFB expression. Immunofluorescence staining revealed a correlation between stromal CFB expression in the tumor microenvironment and an enrichment of immunosuppressive regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We also found that high stromal CFB expression showed a positive correlation with high CD8+/Foxp3+ Tregs populations in PDAC tissues. CONCLUSIONS: Our data indicate that CFB, a key secreted protein, promotes proliferation by preventing cellular senescence and is associated with immunological tumor promotion in PDAC. These findings suggest that CFB may be a potential target for the treatment of PDAC.

Usefulness of the MALDI-TOF MS technology with membrane filter protocol for the rapid identification of microorganisms in perioperative drainage fluids of hepatobiliary pancreatic surgery.

Surgical site infections (SSIs) are significant and frequent perioperative complications, occurring due to the contamination of the surgical site. The late detection of SSIs, especially organ/space SSIs which are the more difficult to treat, often leads to severe complications. An effective method that can identify bacteria with a high accuracy, leading to the early detection of organ/space SSIs, is needed. Ninety-eight drainage fluid samples obtained from 22 patients with hepatobiliary pancreatic disease were analyzed to identify microorganisms using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) with a new membrane filtration protocol and rapid BACpro® pretreatment compared to sole rapid BACpro® pretreatment. The levels of detail of rapid BACpro® pretreatment with or without filtration were also evaluated for the accuracy of bacterial identification. We found that reliable scores for E. coli and E. faecalis were obtained by inoculation with 1.0 × 104 CFU/ml after preparation of the membrane filter with rapid BACpro®, indicating approximately 10-folds more sensitive compared to sole rapid BACpro® pretreatment in drainage fluid specimens. Among 60 bacterial positive colonies in drainage fluid specimens, the MALDI-TOF MS and the membrane filtration with rapid BACpro® identified 53 isolates (88.3%) with a significantly higher accuracy, compared to 25 isolates in the rapid BACpro® pretreatment group (41.7%) (p < 0.001). Among the 78 strains, 14 enteric Gram-negative bacteria (93.0%) and 55 Gram-positive cocci (87.3%) were correctly identified by the membrane filtration with rapid BACpro® with a high reliability. This novel protocol could identify bacterial species within 30 min, at $2-$3 per sample, thus leading to cost and time savings. MALDI-TOF MS with membrane filter and rapid BACpro® is a quick and reliable method for bacterial identification in drainage fluids. The shortened analysis time will enable earlier selection of suitable antibiotics for treatment of organ/space SSIs to improve patients' outcomes.

Simultaneous brain and lung metastases of pancreatic ductal adenocarcinoma after curative pancreatectomy: a case report and literature review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient's condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood-brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. CONCLUSION: We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.

Outcome of interventional radiology for delayed postoperative hemorrhage in hepatobiliary and pancreatic surgery.

BACKGROUND AND AIM: Postoperative hemorrhage is a rare but potentially lethal complication of hepatobiliary and pancreatic surgeries. This study aimed to retrospectively evaluate the clinical outcome of patients with delayed postoperative hemorrhage and compare the results according to the surgical procedure. METHODS: Overall, 4220 patients underwent surgery for hepatobiliary and pancreatic diseases. Delayed postoperative hemorrhage (observed more than 24 h postoperatively) occurred in 62 patients. Of these, 61 underwent interventional radiology to achieve hemostasis. Patients' clinical data were analyzed retrospectively. The chi-squared or Fisher's exact test was used in data analysis. RESULTS: A total of 62 patients (1.5%) developed delayed postoperative hemorrhage; 61 (1.4%) of them underwent interventional radiology to achieve hemostasis. Median duration from surgery to interventional radiology was 19 days (range: 5-252 days). Sentinel bleeding was detected in 31 patients; Clinical success was achieved in 54 patients (88.5%) by interventional radiology. Overall mortality rate was 26.2%. Causes of 16 in-hospital deaths were uncontrollable hemorrhage (n = 4) and worsening of general condition after hemostasis (n = 12). Mortality rates were 50.0% (11/22) and 12.8% (5/39) after hepatobiliary surgery and pancreatic resection, respectively. Mortality rate was significantly higher after hepatobiliary surgery than after pancreatic surgery (P = 0.002). CONCLUSIONS: Interventional radiology can be successfully performed to achieve hemostasis for delayed hemorrhage after hepatobiliary and pancreatic surgeries. Because successful interventional radiology does not necessarily lead to survival, particularly after hepatobiliary surgery, meticulous attention to prevent surgical complications and intensive treatments before and after interventional radiology are required to improve outcomes.

[A Case of Anaplastic Carcinoma with Osteoclastlike Giant Cells of the Pancreas Concomitant with Lung Recurrence of Solitary Fibrous Tumor].

A 32-year-old woman presented with epigastric pain and an abdominal mass. Abdominal CT showed a 130mm pancreatic tail mass with an enhanced rim, central necrosis, and small calcification. A 6mm lung tumor was also found via chest CT. Her medical history included surgical resection of cerebral solitary fibrous tumor when she was 24 years old. When she was 31 years old, it had recurred but was cured by gamma knife radiosurgery. We performed distal pancreatectomy and splenectomy with lymph node dissection. According to pathological and immunohistochemical findings, it was diagnosed as an anaplastic carcinoma with osteoclast-like giant cells. She underwent surgical resection of the lung tumor 2 months after pancreatic resection and was diagnosed with metastasis from the solitary fibrous tumor. Fourteen months since undergoing pancreatectomy, the patient experienced no recurrence from both diseases. We report a rare resected case of anaplastic carcinoma of pancreas concomitant with recurrent solitary fibrous tumor.

High expression of Krüppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer.

Krüppel-like factor 5 (KLF5) plays an oncogenic role and has diverse functions in cancer cells. However, correlation between KLF5 and clinical outcome has not been determined in patients with colorectal cancer and colorectal liver metastasis. Herein, we analyzed 65 patients with colorectal cancer who developed colorectal liver metastasis. Clinical effects were assessed through immunohistochemical analysis of primary colorectal cancer lesions and metastatic liver lesions. High expression of KLF5 in these tissues correlated with the presence of vascular invasion, elevated serum carbohydrate antigen 19-9 levels, large diameters of metastatic liver tumors, and poor prognosis following surgery. Multivariate analyses revealed that high expression of KLF5 was an independent prognostic factor. Increased expression of KLF5 in both colorectal cancer primaries and colorectal liver metastasis was significantly associated with shorter overall survival time and time to surgical failure. Krüppel-like factor 5 expression positively correlated with Ki-67 and c-Myc expression in colorectal cancer tissues. In vitro experiments with colon cancer cell lines showed that siRNA knockdown of KLF5 inhibited cell proliferation. Western blot analyses revealed that knockdown of KLF5 expression reduced cyclin D1 and c-Myc expression. It also impaired the stem cell-like properties of cancer cells in tumorsphere formation assays. Furthermore, anoikis assay indicated that KLF5 contributed to anoikis resistance. High KLF5 expression is associated with poor prognosis in patients with colorectal cancer and liver metastasis by promoting cell proliferation and cancer stem cell-like properties.

Long-term outcomes and significance of preoperative lymphocyte-to-monocyte ratio as a prognostic indicator in patients with invasive pancreatic neoplasms after repeat pancreatectomy.

BACKGROUND: Invasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called "repeat pancreatectomy" to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors. METHODS: Twenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models. RESULTS: Of 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan-Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis. CONCLUSIONS: Preoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.

Needle tract seeding recurrence of pancreatic cancer in the gastric wall with paragastric lymph node metastasis after endoscopic ultrasound-guided fine needle aspiration followed by pancreatectomy: a case report and literature review.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging. CASE PRESENTATION: An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19-9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing. CONCLUSION: It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.

[A Case of Long-Term Survival in a Patient with Recurrence of Peritoneal Dissemination after Resection of Pancreatic Tail Cancer].

A 60-year-old man underwent distal pancreatectomy with splenectomy and combined resection partially of the stomach, jejunum, and left renal vein. We administered S-1 adjuvant chemotherapy for 1 year. After its completion, the patient showed no evidence of recurrence. However, his carbohydrate antigen(CA)19-9 level was elevated for 1 year and 8 months postoperatively. We administered gemcitabine chemotherapy. He was admitted for bowel obstruction 3 years and 10 months postoperatively. Conservative treatment with an ileus tube did not improve the bowel obstruction. Therefore, we performed the surgery. Intraoperative findings revealed peritoneal nodules invading the small intestine. We performed a small bowel bypass. Pathological examination revealed the peritoneal nodule of pancreatic cancer. Although we administered FOLFIRINOX chemotherapy postoperatively, his CA19-9 level remained elevated for 4 years and 8 months after the first surgery. Therefore, chemotherapy was changed to gemcitabine and nab-paclitaxel. Six years and 11 months after the first surgery and 5 years and 3 months after the diagnosis of peritoneal dissemination, he survives with recurrence. Herein, there were 2 contributors to long-term survival; the patient not only showed positive responses to each chemotherapy regimen but could also continue chemotherapy without developing significant adverse effects.

[A Case of Pancreatic Mucinous Cystic Carcinoma with Bilateral Lung Metastases].

A 48-year-old female visited former doctor with abdominal pain and bloating. She was suspected of having pancreatic tumor and referred to our hospital. Abdominal dynamic CT showed multilocular cystic tumor in the pancreatic tail, and chest CT showed multiple lung nodules. From these findings, the patient was diagnosed mucinous cystic carcinoma(MCC)with lung metastases. We performed distal pancreatectomy for the first and lung resection after pancreatectomy. After all, the pathological diagnosis was MCC and metastatic lung cancer from the MCC. The adjuvant chemotherapy was not performed. Eleven months after pancreatectomy and 6 months after lung resection, the patient is still alive without recurrence.

Is hepatic artery coil embolization useful in distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic cancer?

BACKGROUND: The exact contribution of preoperative coil embolization in distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for the prevention of ischemic liver complication is not fully elucidated. METHODS: From January 2004 to July 2015, 31 patients underwent DP-CAR for the pancreatic body-tail cancer. Twenty-three patients received preoperative coil embolization. The characteristics and operative outcomes were analyzed retrospectively. RESULTS: The median survival time and 1- and 3-year overall survival rates were 23.7 months and 74.2% and 34.4%, respectively. No 30-day mortality occurred in any of the patients. Postoperative liver infarction developed only in 8 patients (25.8%) even though 7 of 8 patients had undergone preoperative coil embolization. Tumor contact with the gastroduodenal artery (GDA)/proper hepatic artery (PHA) on preoperative multi-detector computed tomography (MDCT), tumor size, operative time, portal vein resection, and stenosis of the GDA/PHA after DP-CAR are related to liver infarction. Among them, postoperative stenosis of the GDA/PHA on MDCT, which was observed in all 8 patients with liver infarction, was the most closely related factor to postoperative liver infarction. Tumor contact with the GDA/PHA did not worsen the R0 resection rate or overall survival rate. CONCLUSION: Our data indicate that preoperative coil embolization of the common hepatic artery is not useful in DP-CAR as long as GDA is completely preserved during surgery.

Successful treatment of a locally advanced unresectable pancreatic cancer patient with interstitial pneumonitis by conversion surgery following gemcitabine plus nab-paclitaxel chemotherapy: A case report.

Conversion surgery is an attractive strategy to improve the outcomes for locally advanced unresectable (UR-LA) pancreatic ductal adenocarcinoma (PDAC). The present case report, presents a case of successful conversion surgery following the treatment of a patient with UR-LA PDAC, suffering from interstitial pneumonitis (IP), using a combination of gemcitabine and nab-paclitaxel (GnP). A 67-year-old woman presented at the hospital with a high level of carbohydrate antigen 19-9 (CA19-9; 1,713 U/ml). Radiological examination revealed a pancreatic tumor in contact with the superior mesenteric artery, with invasion extending to the most proximal draining jejunal branch into the superior mesenteric vein. The patient was diagnosed with UR-LA PDAC. Following 6 courses of GnP therapy, the tumor size markedly decreased from 50 to 18 mm, and the level of CA19-9 also decreased from 1,713 to 60.1 U/ml. Due to the progression of IP, the patient was administered steroid medication along with a restart of tacrolimus for the treatment of dermatomyositis and IP. After recovery from her lung condition, an additional 3 courses of GnP therapy were administered, and then pancreatoduodenectomy was performed. The patient was still alive 14 months post-surgery with no recurrence. Between July 2009 and September 2017, conversion surgery was performed for 18 cases of UR-LA PDAC treated with gemcitabine plus S-1 (GS) therapy, and 11 cases with GnP therapy. The percentage of median CA19-9 and median tumor volume reductions were 73.7 and 51.6%, respectively, following GS therapy, and 86.7 and 68.8%, respectively, following GnP therapy. Tumor reduction following GnP therapy was significantly higher than that after GS therapy (P=0.02). GnP therapy is a suitable regimen to shrink the tumor mass in patients with UR-LA PDAC. Careful management of systemic conditions is required to treat patients with PDAC and IP when using GnP therapy. Conversion surgery should be considered for recognizing radiological responses (tumor shrinkage adjacent to major arteries) and reductions in CA19-9 levels.

Feasibility and safety of distal pancreatectomy with en bloc celiac axis resection (DP-CAR) combined with neoadjuvant therapy for borderline resectable and unresectable pancreatic body/tail cancer.

PURPOSE: Pancreatic body/tail cancer commonly invades the hepatic artery or celiac artery, making surgical resection difficult. Distal pancreatectomy with celiac axis resection (DP-CAR) has recently been performed to achieve curative resection of these tumors. However, the safety and efficacy remain unclear. This study aimed to clarify the efficacy and safety of DP-CAR, mainly focusing on the combination with neoadjuvant therapy (NAT). METHODS: We retrospectively reviewed 31 consecutive patients with pancreatic ductal adenocarcinoma who underwent DP-CAR between 2010 and 2016. Data from 7 patients who underwent DP-CAR without NAT were used as a reference (upfront surgery, US). RESULTS: Gemcitabine + S-1 (GS) (n = 17) and gemcitabine + albumin-bound paclitaxel (GnP) (n = 8) were frequently used as NAT. DP-CAR following NAT was performed safely with 1 death, resulting in a mortality rate of 3%. The median survival time (MST) in the NAT group was 38.6 months, while that in the US group was 15.6 months. The NAT group had a high R0 resection rate (74%), while only 1 of 7 cases in the US group achieved R0 resection. Within the NAT group, patients treated with GS showed favorable overall survival with 39.5 months of MST, while that of patients treated with GnP was 19.8 months. CONCLUSION: The combination of NAT and DP-CAR was feasible and safe for pancreatic body/tail cancer invading the celiac artery and/or hepatic artery. This strategy should be further assessed for the optimal regimen and duration of NAT in prospective studies.

Ischemic gastropathy after distal pancreatectomy with en bloc celiac axis resection versus distal pancreatectomy for pancreatic body/tail cancer.

BACKGROUND: Ischemic gastropathy (IG) is a major complication after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for locally advanced body/tail pancreatic ductal adenocarcinoma (PDAC), and its incidence is still unknown. METHODS: To evaluate the occurrence of IG, 77 and 18 consecutive patients with body/tail PDAC were analyzed in a retrospective and a prospective study, respectively. We utilized perioperative gastroendoscopy, Gastrointestinal Quality of Life Index (GIQLI) score, and quantitative assessment for gastric arterial blood flow using the HyperEye Medical System (HEMS) with indocyanine green (ICG) fluorescence imaging in the prospective arm. RESULTS: In the retrospective arm, no significant difference was noted in the occurrence rate of IG between the DP-CAR (8.7%) and DP groups (5.5%). In the prospective arm, the postoperative endoscopic scores were significantly higher in the DP-CAR group (45%) than in the DP group (11%) (p < .0007) despite no difference in the GIQLI score. The ICG-HEMS imaging system demonstrated more delayed arterial flow velocity in the IG (+) group (p < .028), but showed no significant difference in arterial flow volume compared to the IG (-) group. CONCLUSION: This is the first demonstration assessing IG incidence after DP-CAR using multiple methods. Despite the high IG rate, gastric arterial flow volume was almost equally maintained in DP-CAR patients with or without IG compared with the DP group. We should note the fact that many of the IG patients do not present with typical symptoms, and proper treatment is required for those "silent" IG patients.

[Anaplastic Carcinoma of the Pancreas of the Spindle Cell Type with Rapid Growth and Liver Metastases after Resection-A Case Report].

An 81-year-old man was referred to our department because of rapid progression of a cystic lesion in the pancreatic tail. Abdominal CT revealed a heterogeneously enhancing tumor, measuring 70mm in diameter, in the pancreatic tail, encompassing a low-density area with calcification and directly invading the spleen. We diagnosed the patient with malignant transformation of solid-pseudopapillary neoplasm and performed distal pancreatectomy with splenectomy, partial transverse colectomy, and partial resection of the diaphragm. Histopathological examination revealed anaplastic carcinoma of the pancreas of the spindle cell type, and R0 resection was achieved. Anastomotic leakage of the transverse colon occurred on postoperative day 4, and ileostomy was performed. Multiple liver metastases were observed on postoperative day 27, and the patient was orally administered with S-1. Although he was discharged on postoperative day 50, he died of cancer on postoperative day 61. Anaplastic carcinoma of the pancreas has a poor prognosis, and an early multidisciplinary treatment should be performed.