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Recently, several scholars have demonstrated the efficacy of carbon ion radiotherapy (CIRT). To treat abdominal or pelvic tumors by CIRT, it is necessary to separate the tumor from the adjacent organs. Surgical placement of a GORE-TEX sheet as a spacer has been reported as a separation method. Usually, surgical spacer placement is done by open surgery. Here, we report a case of surgical spacer placement undertaken by a "pure" laparoscopic procedure. A 47-year-old man with recurrent sacral chordoma was referred for surgical spacer placement before CIRT. Laparoscopic dissection of the rectum and placement of a GORE-TEX sheet as a spacer were successfully performed. Surgical spacer placement by a pure laparoscopic procedure was safe and effective, and it seems to play an important part before CIRT.

Background: Immune checkpoint inhibitors (ICIs) has become a new promising treatment in the field of cancer therapy. Therefore, it is important to identify predictors of effect for ICIs in breast cancers (BC). PD-L1 expression and the abundance of TILs were known to be related to tumor mutational burden (TMB). TMB is associated with clinical benefit to ICIs in patients with melanoma, lung and colon cancer. However, the significance of TMB is unclear in BC. In this study, we assessed TMB using the TruSightOncology 500 panel (TSO500) (Illumina, San Diego), which the US Food and Drug Administration had designated as a breakthrough device, and identify characteristics of higher TMB tumors in triple negative breast cancer (TNBC), one of the most clinically aggressive subtypes. Methods: This study included 30 patients with primary TNBC underwent resection without neoadjuvant chemotherapy. DNA was extracted from FFPE tissue. Next-generation sequencing assay was performed by using the TSO500. The DNA of 523 genes for assessment of small variants, as well as biomarkers related to response to immunotherapy, such as TMB and MSI. TMB was measured in synonymous and/or non-synonymous mutation (mut) per megabase (mb). Total TMB levels were divided into three groups: low (1-5 mut/mb), intermediate (int) (6-19 mut/mb), and high (≥20 mut/mb). PD-L1 were assessed in IHC staining and PD-L1 positivity was defined as PD-L1 expression in ≥1% of tumor cells. TILs were assessed in HE staining and TILs were defined as TILs-high for ≥50% stromal TILs and TILs-low for Results: The median age of patients was 63 years old (range: 32-81). The median TMB was 8.56 mut/mb (2.35-14.22). Among the 30 tumors, 8 (26.7%) were TMB-low, 22 (73.3%) were TMB-int, and none was TMB-high. TMB-int tumors had more aggressive features than TMB-low tumors. In TMB-int tumors, nuclear grade 3 were 72.7%, high labeling index of Ki-67 (≥20%) were 54.5%, and PD-L1 positivity on tumor cells were 68.2%. Whereas, PD-L1 positivity were 25.0% in TMB-low tumors (p=0.03). TILs-high were 72.7% in TMB-int and TILs-low were 75.0% in TMB-low (p=0.02). Twelve patients in TMB-int (54.5%) and 1 patient in TMB-low (12.5%) were treated by anthracycline based chemotherapy as an adjuvant chemotherapy. Six patients with TMB-int had recurred within 5 years and 3 of them died. Meanwhile, no one with TMB-low had recurred and died. Conclusions: Findings of our study demonstrated that higher TMB in TNBC might be a poor prognostic factor. We could expect this breakthrough device to be useful for the treatment strategy in patients with TNBC. Citation Format: Kanako Kurata, Makoto Kubo, Yuan Yuan, Yurina Harada, Takafumi Morisaki, Akiko Shimazaki, Saori Hayashi, Hitomi Kawaji, Kazuhisa Kaneshiro, Mai Yamada, Masaya Kai, Masafumi Nakamura. Tumor mutational burden in Japanese patients with triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-08.

Background: Oncogenic genetic alterations leading to identify patients who may benefit from the target therapy are essential biomarkers for them, and to review widely what kind of driver gene alteration that each cancer has is important for effective cancer treatments. Next-generation sequencing (NGS) is a powerful tool to comprehensively analyze driver gene mutations. In Japan, some multiplex cancer genetic testings were covered from national health insurance from June, 2019. Therefore, we reviewed our data using a targeted NGS platform (FoundationOne CDx (F1CDx)) in Japanese breast cancer patients. Methods: This study included 105 local advanced or metastatic breast cancer patients in Kyushu University Hospital between October 2018 and June 2019. We prospectively assessed NGS results, clinical characteristics and therapies received for the patients. Primary endpoint was a frequency at which actionable genetic alterations were detected, and coprimary secondary endpoints were the sequence success rate, the rate at which the corresponding therapeutic agent was administered, the percentage of agreement to results with approved in vitro diagnostic agents, and the overall survival. This study was approved by the Institutional Review Board of our hospital (No. 758-00). Results: Samples from 105 breast cancer patients were tested, all of who were women. Then, 99 samples (94.3 %) were success for sequencing and 6 (5.7 %) were failure. Among the succeeded samples, tested from primary tumor is 71 (71.7 %) and metastasis is 34 (34.3 %), while 62 (62.6 %) were biopsied tumor specimen and 43 (37.4 %) resected. The clinical subtypes of them were 45 HR +/ HER2 - (45.5 %), 22 HER2+ (22.2 %), and 32 TNBC (32.3 %). Based on the biomarker findings from F1CDx, microsatellite statuses in 97 samples were stable and 1 sample high, who was diagnosed with Lynch syndrome. Regarding tumor mutation burden (TMB), of 98 patients, 3 had high TMB (>19 mutations/mb), 31 had intermediate TMB (6-19 mutations/mb), 63 had low TMB (1-5 mutations/mb) and 1 were unable to be determinated. The average was 6.7 mutations/mb. The most frequent alteration is TP53 (54.5 %), PIK3CA (39.4 %) and ERBB2 (29.3 %). 87 patients (87.8 %) detected the alterations leading to some therapeutic options based on genetic profiling. 25 patients with metastases had taken genetic testing for BRCA1/2 germline mutation (gBRCA1/2mut), which isnamed BRACAnalysis. In all of 5 patients who had gBRCA1/2muts the same spot mutations were also detected with F1CDx. In 2 of 20 patients had negative gBRCA1/2mut, somatic BRCA1/2muts were newly detected with F1CDx. In 9 of the other patients had not taken the genetic testing, somatic BRCA1/2muts were founded. 18 tumors with HER2/Immunohistochemical staining (IHC) =3+ were judged as ERBB2 amplification, 3 tumors with HER2/IHC=2+ and HER2/FISH positive as low amplification, and 18 tumors with HER2/IHC=2+ and HER2/FISH negative as no amplification. Moreover, there are were 3 patients who newly confirmed ERBB2 amplification and 4 patients who confirmed ERBB2 mutations in this study. Conclusions: The multiplex cancer genetic testing could help identify actionable alterations for the breast cancer patients. NGS results may add some new therapeutic options to standard therapies. Citation Format: Hitomi Kawaji, Makoto Kubo, Nami Yamashita, Yurina Harada, Akiko Shimazaki, Saori Hayashi, Kanako Kurata, Mai Yamada, Kazuhisa Kaneshiro, Masaya Kai, Eiji Baba, Yoshinao Oda, Masafumi Nakamura. A prospective evaluation of comprehensive tumor profiling busing a targeted Next-generation sequencing for Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-12.

[background] In general, TNBC has a high distant metastasis rate and is highly aggressive. Despite good response to chemotherapy, it has a poorer prognosis compared to other subtypes. There is a need to develop new treatments for the selection of appropriate treatments. At present, treatments using an immune check point blockade are attracting attention, and the evaluations as biomarkers of and, PD-1 / PD-L1 expression on immune cells for therapeutic effects and prognosis in TNBC are controversial. In order to select patients with TNBC for who immunotherapy is likely to be effective, new biomarkers need to be explored. [Purpose] Our aim is to investigate the possibility as a biomarker of PD-L1 expression on immune cells(PD-L1/IC) in TNBC. We also assess the relationship among PD-L1/IC, PD-L1 expression on tumor cells(PD-L1/TC) and TIL. [Methods] This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital(Fukuoka, Japan) and related hospitals between January 2004 and December 2014. [Results] PD-L1/IC was positive in 129 cases (52.0%) of 248 TNBCs. Although there was no significant difference in RFS and OS between the positive and negative groups, PD-L1/IC-positive and TIL-High group showed the best prognosis, considering the combination whether PD-L1/IC was positive or negative, and TIL was high or low. PD-L1/IC was significantly correlated with PD-L1/TC(p [Conclusion] In TNBC, the relationship between PD-L1/IC and prognosis is still not clear, but in IMpassion130 trial, PD-L1/IC is a predictive marker for the effect of Atezolizumab. PD-L1/IC has potential as an immune biomarker in TNBCs. This study also found that PD-L1/IC was related to the therapeutic effect of anthracycline. PD-L1/IC may be a predictive marker of the efficacy of various treatments. Citation Format: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura. PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-21.

Recently, several scholars have demonstrated the efficacy of carbon ion radiotherapy (CIRT). To treat abdominal or pelvic tumors by CIRT, it is necessary to separate the tumor from the adjacent organs. Surgical placement of a GORE-TEX sheet as a spacer has been reported as a separation method. Usually, surgical spacer placement is done by open surgery. Here, we report a case of surgical spacer placement undertaken by a "pure" laparoscopic procedure. A 47-year-old man with recurrent sacral chordoma was referred for surgical spacer placement before CIRT. Laparoscopic dissection of the rectum and placement of a GORE-TEX sheet as a spacer were successfully performed. Surgical spacer placement by a pure laparoscopic procedure was safe and effective, and it seems to play an important part before CIRT.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Rationale: Pancreatic cancer is one of the most difficult cancers to manage and its poor prognosis stems from the lack of a reliable early disease biomarker coupled with its highly metastatic potential. Liver metastasis accounts for the high mortality rate in pancreatic cancer. Therefore, a better understanding of the mechanism(s) underlying the acquisition of the metastatic potential in pancreatic cancer is highly desirable. Methods: Microarray analysis in wild-type and highly liver metastatic human pancreatic cancer cell lines was performed to identify gene expression signatures that underlie the metastatic process. We validated our findings in patient samples, nude mice, cell lines and database analysis. Results: We identified a metastasis-related gene, laminin subunit alpha 4 (LAMA4), that was upregulated in highly liver metastatic human pancreatic cancer cell lines. Downregulation of LAMA4 reduced the liver metastatic ability of pancreatic cancer cells in vivo. Furthermore, LAMA4 expression was positively correlated with tumor severity and in silico analyses revealed that LAMA4 was associated with altered tumor microenvironment. In particular, our in vitro and in vivo results showed that LAMA4 expression was highly correlated with cancer-associated fibroblasts (CAFs) level which may contribute to pancreatic cancer metastasis. We further found that LAMA4 had a positive effect on the recruitment and activity of CAFs. Conclusions: These data provide evidence for LAMA4 as a possible biomarker of disease progression and poor prognosis in pancreatic cancer. Our findings indicate that LAMA4 may contribute to pancreatic cancer metastasis via recruitment or activation of CAFs.

BackgroundIt is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations. However, the frequency of MSI in Japanese TNBCs still remains unclear. We aimed to analyze the presence of MSI-H in TNBCs as a biomarker for ICI therapy.MethodsIn this study, we retrospectively evaluated the MSI of 228 TNBCs using an innovative method, MSI Analysis System Version 1.2 (Promega), consisting of 5 microsatellite markers: BAT-26, NR-21, BAT-25, MONO-27 and NR-24 without a normal tissue control.ResultsAmong 228 tumors, 222 (97.4%) were microsatellite stable, 4 (1.7%) low-frequency MSI and 2 (0.9%) MSI-H, respectively. Two MSI-H tumors were potentially aggressive pathologically as indicated by nuclear grade 3 and high Ki-67 (> 30%), and were classified as basal-like and non-BRCA-like, but were not consistent regarding tumor-infiltrating lymphocytes, CD8 and PD-L1 expression.ConclusionsAlthough we found that MSI-H was uncommon (0.9%) in TNBCs, potential targets for ICIs exist in TNBCs. Therefore, MSI-H breast cancer patients should be picked up using not only conventional methods but also platforms for comprehensive genomic profiling.

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA., Solid‐type poorly differentiated adenocarcinomas of the stomach showed frequent losses of mismatch repair proteins and SWI/SNF complex, suggesting that the loss of SWI/SNF complex could induce a solid morphology.

Hypoxia is a characteristic feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). We have recently explored new targeting molecules and pathways in PDAC cells under hypoxic conditions. In this study, we performed a microarray experiment to analyze the genes up-regulated in PDAC cell lines under hypoxia compared to normoxia, and identified human family with sequence similarity 115, member C (FAM115C) as a candidate gene for further study. Our data showed that FAM115C was overexpressed in PDAC cell lines under hypoxia, and FAM115C inhibition promoted PDAC cell migration and invasion in vitro. FAM115C inhibition did not affect tumor cell proliferation in PDAC. Immunohistochemically, FAM115C expression was observed ubiquitously in normal pancreas, pancreatic intraepithelial neoplasia (PanIN) and PDAC tissue, and it was located mainly in the nucleus but also in the cytoplasm of cells. In qPCR analysis, high expression of FAM115C was correlated with better prognosis in patients with PDAC. Our findings suggest that FAM115C could be a novel tumor suppressor associated with prolonged survival in patients with PDAC.

The aim of this study was to describe the factors associated with growth before and after kidney transplant.We retrospectively reviewed 60 pediatric patients with end-stage kidney disease aged ≤16 years who underwent kidney transplant at our facility between November 2001 and March 2018. Height standard deviation score and possible associated factors were also compared.Among the 60 patients, median age was 11 years (interquartile range, 5.3-14 years), and 24 (40%) were female. All patients were alive during the observational period. The 2-, 5-, and 15-year graft survival rates were 96.7%, 94.4%, and 77.8%, respectively. Mean height standard deviation score for preoperative kidney transplant was -2.1 ± 1.5. Duration of dialysis (months) was associated with preoperative height standard deviation score (β = -0.020; standard error = 0.006; t = -3.23; P = .002).Higher age andepisode of rejection were significant factors for loss of catch-up growth (P.001 and P = .023, respectively). In total, 26 patients (43.3%) and 19 patients (31.7%) had short stature preoperatively and at 2 years after kidney transplant, respectively. Although 23 patients (38.3%) presented with catch-up growth after kidney transplant, 14 (53.9%) remained with short stature even 2 years after kidney transplant.Height standard deviation score 2 years after kidney transplant was associated with age, preoperative height standard deviation score, and episodes of rejection (P = .032, P.001, and P = .005, respectively).Our study suggests that, although kidney transplant results in catch-up growth in pediatric patients, short stature often persists even 2 years after kidney transplant and is affected by age, preoperative height standard deviation score, and episodes of rejection.

Background Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021). Methods Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network (SIGN) methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. Results Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts. Conclusions The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide.

The combined resection of the vesical artery (VA) in laparoscopic lateral pelvic lymph node dissection (L-LPLD) was reported to facilitate the safe dissection of metastatic lymph nodes. However, whether or not the combined VA resection affects the urinary function remains controversial.The purpose of the present study was to examine the risk factors for the postoperative urinary dysfunction (PUD) after L-LPLD followed by total mesorectal excision and to clarify the effects of the combined VA resection in L-LPLD on PUD.L-LPLD was performed in 95 patients with advanced rectal cancer at Saga University Hospital and Kyushu University Hospital from January 2013 to December 2017. The risk factors for PUD after L-LPLD were investigated.The univariate analysis revealed that the combined resection of the inferior vesical artery (IVA) was a risk factor for PUD. To examine by the type of IVA resection, the incidence of PUD significantly increased with the bilateral IVA resection, but the unilateral IVA resection induced PUD on the same level with the preservation of IVA.Bilateral IVA resection in L-LPLD could increase the incidence of PUD. Thus, if possible, the preservation of the unilateral IVA through L-LPLD should be considered.

Mucinous cystic neoplasm (MCN) of the pancreas rarely progresses to invasive carcinoma, but few studies have analyzed genomic alterations involved in its malignant transformation. The relationships of ring finger protein 43 (RNF43) mutations with cytological atypia, RNF43 protein expression, and Wnt signaling proteins in MCN remain unclear. This study included 106 MCN cases, classified into 89 low-grade dysplasia (LG), 9 high-grade dysplasia (HG), and 8 invasive carcinoma (INV). We analyzed HG/INV and LG lesions of 9 HG/INV cases and LG lesions of 9 LG cases using targeted sequencing and confirmed the protein expression of RNF43 and β-catenin. The frequency of RNF43 mutations was significantly higher in HG/INV cases than in LG cases. Furthermore, HG/INV lesions (56%) and LG lesions (33%) of HG/INV cases possessed RNF43 mutation, whereas no such mutation was detected in any LG cases. The expression of RNF43 was reduced in 71% of HG/INV cases and significantly correlated with histological grade and aberrant expression of β-catenin. In 3 of 5 RNF43-mutated cases, the expression of RNF43 was reduced, but there was no significant correlation between RNF43 mutation and protein expression. MCNs frequently harbored KRAS mutations, at rates of 100% in HG/INV lesions and 50% in LG lesions of HG/INV and LG cases. There was no significant difference in mutation frequency in LG lesions between HG/INV and LG cases. These results suggest that RNF43 mutations may be involved in and predictive of malignant transformation from an early stage of MCN.

The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021.The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations.This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed.The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

Supplemental Digital Content is available in the text., Background. Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can be used effectively and safely in kidney transplant (KT) recipients with pretransplant type 2 diabetes as the primary cause of end-stage renal disease (ESRD) remains unclear. In this study, we retrospectively analyzed the efficacy and safety of SGLT2 inhibitors compared with other oral hypoglycemic agents (OHAs) in KT recipients with pretransplant type 2 diabetes as the primary cause of ESRD. Methods. In this retrospective, observational, single-center, inverse probability of treatment weighting (IPTW) analysis study, we compared the outcomes of SGLT2 inhibitors (SGLT2 group) and other OHAs (control group) following KT. A total of 85 recipients with type 2 diabetic nephropathy as the major cause of ESRD before KT who were treated at our institute between October 2003 and October 2019 were screened and included. The variables considered for IPTW were recipient age, sex, body mass index, history of cardiovascular disease, ABO incompatibility, insulin therapy, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) at the initiation of additional OHAs. Primary endpoints were changes in HbA1c, body weight, and eGFR 1 y after the initiation of additional OHAs. Results. After IPTW analysis, there were 26 patients in the SGLT2 group and 59 patients in the control group (n = 85 overall). The body weights were significantly reduced in the SGLT2 group. There was no statistical difference in changes in HbA1c and eGFR. Similarly, there was no significant difference in the incidence of urinary infection, acute rejection, or other side effects between the groups. Conclusions. Our findings suggested that SGLT2 inhibitors reduced the body weight of KT recipients and were used safely without increasing side effects.

Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses. Methods The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared. Results The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs. Conclusions Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies.

This study found distribution of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and dioxin like polychlorinated biphenyls (DL-PCBs) in bovine milk and ash samples collected from 9 different major districts namely Erode, Salem, Namakkal, Coimbatore, Trippur, Madurai, Chennai, Dindigul and Tiruchirappalli, which were highly populated and industrialized districts of South India (Tamil Nadu). The total toxic equivalency (TEQ) for PCDD/Fs and DL-PCBs in the bovine milk samples were ranged from 0.028 to 7.331-pg TEQ/g fat. Some of the districts showed higher PCDD/Fs and DL-PCBs concentration in milk and ash samples. Further, BM14 (7.331 pg-TEQ/g fat) and BM21 (6.406 pg-TEQ/g fat) sampling sites showed exceed level of PCDD/Fs and DL-PCBs than WHO regulation limits (6 pg-TEQ/g fat). Similarly, Total dioxins and DL-PCBs concentration in the ash sample were between 0.003-1. ng TEQ/g. Samples from AS3 (1.2 ng-TEQ/g) and AS11 (1.06 ng-TEQ/g) showed higher total dioxins and DL-PCBs level among other sampling sites. This study provides an overview of dioxins and dioxin-related compounds contamination in bovine milk and ash samples in south Tamil Nadu. Further, the CALUX assay method validation has simplified the monitoring of dioxin contamination in the environment.

Background The concept of Minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). Methods Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network (SIGN) method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. Results Seven Clinical Questions (CQs) were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. Conclusions The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.

Highlights • PTPN3 suppression associates with lymphocyte activation and cancer suppression. • PTPN3 is involved in the induction of malignant traits. • PTPN3 is associated with cellular immunosuppression. • Signals from PTPN3 go through MAPK and PI3K signaling. • PTPN3-inhibited lung NET cells enhance PTPN3-suppressed activated lymphocytes., In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC). Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.

Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cancer-derived fibroblasts and normal fibroblasts were used, and the pathway analysis suggested altered pathways that were chosen for validation. It was found that the 'neuroactive ligand-receptor interaction' pathway from the Kyoto Encyclopedia of Genes and Genomes pathway analysis was one of the altered pathways. Several compounds related with this pathway were chosen, and changes in PSC activity were investigated using fluorescence staining of lipid droplets, reverse transcription-quantitative PCR, western blotting, and invasion and migration assays. Among these candidates, duloxetine, a serotonin-noradrenaline reuptake inhibitor, was found to suppress PSC activation and disrupt tumor-stromal interaction. Thus, duloxetine may be a potential drug for suppressing PSC activation and pancreatic cancer growth.

Background : Schizophrenia is a devastating mental disease that affects approximately 1% of the world's population. Breast cancer is the second most common type of cancer in the world that causes death in women. It is often unclear whether patients with schizophrenia receive recommended cancer treatment that met the guideline. This study characterized breast cancer treatment disruptions in schizophrenia patients and sought to identify and resolve correctable predictors of those disruptions. Materials and methods : A retrospective cohort study was conducted on 55 primary breast cancer patients diagnosed with schizophrenia and treated for breast cancer. We evaluated the characteristics of the breast cancer patients with schizophrenia compared to those of 610 breast cancer patients without schizophrenia. Results : Compared to the control group, the schizophrenia group had significantly advanced T and N factors and disease stage. Significantly fewer patients in the schizophrenia group than in the control group received chemotherapy (p Conclusions : Patients with schizophrenia are often diagnosed with breast cancer in advanced stages. In addition, patients with schizophrenia with reduced ADL are less likely to receive chemotherapy or recommended cancer treatment. It is highly recommended that patients with schizophrenia undergo breast cancer screening so that they can be diagnosed early and treated adequately. Micro Abstract : Patients with schizophrenia are often diagnosed with breast cancer in advanced stages. In addition, patients with schizophrenia with reduced ADL are less likely to receive chemotherapy or standard treatment. It is highly recommended that patients with schizophrenia undergo breast cancer screening so that they can be diagnosed early and treated adequately.

To evaluate patients undergoing a new procedure, iliac vascular transposition, in pancreas transplantation regarding the risk of thrombosis and graft survival without heparin-based anticoagulation therapy. Iliac vascular transposition (IVT) involves changing the positions of the external iliac artery and vein relative to each other. In this study, this technique was evaluated in patients undergoing the procedure compared with patients not undergoing the procedure (iliac vascular parallel (IVP) group). No patients received prophylactic heparin therapy. Two patients in the IVP group (n = 26) developed complete thrombosis and six developed partial thrombosis, compared with no patients with complete thrombosis and one with partial thrombosis in the IVT group (n = 29). The cumulative incidence of thrombosis was significantly higher in the IVP group (p

Background/objectives Pancreatic ductal adenocarcinoma (PDAC) is characterized by excessive desmoplasia and autophagy-dependent tumorigenic growth. Pancreatic stellate cells (PSCs) as a predominant stromal cell type play a critical role in PDAC biology. We have previously reported that autophagy facilitates PSC activation, however, the mechanism remains unknown. We investigated the mechanism of autophagy in PSC activation. Methods We compared gene expression profiles between patient-derived PSCs from pancreatic cancer and chronic pancreatitis using a microarray. The stromal expression of target gene in specimen of PDAC patients (n = 63) was analyzed. The effect of target gene on autophagy and activation of PSCs was investigated by small interfering RNAs transfection, and the relationship between autophagy and ER stress was investigated. We analyzed the growth and fibrosis of xenografted tumor by orthotopic models. Results In analysis of gene expression microarray, endoplasmic reticulum aminopeptidase 2 (ERAP2) upregulated in cancer-associated PSCs was identified as the target gene. High stromal ERAP2 expression is associated with a poor prognosis of PDAC patients. Knockdown of ERAP2 inhibited unfolded protein response mediated autophagy, and led to inactivation of PSCs, thereby attenuating tumor-stromal interactions by inhibiting production of IL-6 and fibronectin. In vivo, the promoting effect of PSCs on xenografted tumor growth and fibrosis was inhibited by ERAP2 knockdown. Conclusions Our findings demonstrate a novel mechanism of PSCs activation regulated by autophagy. ERAP2 as a promising therapeutic target may provide a novel strategy for the treatment of PDAC.

Background/aim With advances in anti-HER2 treatment and improved prognoses of HER2-positive breast cancer, the American Society of Clinical Oncology and the American Society of Pathologists (ASCO/CAP) have revised the HER2 diagnostic guidelines several times. We examined how to respond clinically to the revisions of the interpretation of the immunohistochemistry (IHC) method. Patients and methods We re-evaluated 254 patients diagnosed as HER2 IHC equivocal, who underwent fluorescence in situ hybridization (FISH) before and after the IHC diagnostic criteria update in 2013. Results Twenty of 131 (15.3%) IHC equivocal cases by the ASCO/CAP 2007 guideline were IHC score 3+ and one of 20 (0.76%) was negative for FISH. Five of 123 (4.1%) IHC equivocal cases by the ASCO/CAP 2013 guideline were negative for IHC as per the 2007 guideline and four were positive for FISH. Conclusion After revision of the ASCO/CAP 2013 guideline, 3.3% of HER2-negative cases before the revision should have received anti-HER2 treatment.

Introduction: Although neoadjuvant treatment is recommended for patients with borderline resectable pancreatic cancer (BRPC), no standard neoadjuvant regimen has been established for BRPC with arterial involvement (BRPC-A), which is associated with a higher risk of margin-positive resection and poorer prognosis than BRPC with only venous involvement. Gemcitabine plus nab-paclitaxel (GnP) has been reported to significantly reduce tumor size in metastatic pancreatic cancer, and some retrospective studies suggested that neoadjuvant GnP for BRPC improved resectability and survival. Methods and analysis: A prospective multicenter single-arm phase II study is conducted to evaluate the safety and efficacy of GnP as neoadjuvant chemotherapy for BRPC-A. The primary endpoint is the R0 resection rate. The secondary endpoints are the neoadjuvant chemotherapy response rate, resection rate, pathological response rate, incidence rate of adverse events, and quality of life. Ethics and dissemination: This study protocol was approved by the institutional review board of Kyushu University (no. 181). The results will be published in a peer-reviewed journal and will be presented at medical meetings. Highlights: Strategy for borderline resectable pancreatic cancer involving arteries (BRPC-A). There is no standard regimen for neoadjuvant chemotherapy for BRPC-A. Gemcitabine plus nab-paclitaxel (GnP) shows significant tumor shrinkage. Neoadjuvant GnP for BRPC-A increases resectability and margin-negative resection.

Fat suppression is a technique used to suppress the signals from adipose tissues, during clinical evaluation of the tissues near the fat-tissue boundary. However, in cases where the scan area has a complicated shape, the effect of fat suppression may demonstrate poor uniformity, resulting in diagnosis-related difficulties. To improve the uniformity of fat suppression, phantom studies are more suitable than volunteer studies. In this study, we evaluated the reliability of the region of interest (ROI) dependency using an unevenness phantom, to develop a method to assess the uniformity of fat suppression while using whole magnetic resonance imaging by masking the surrounding phantom. We modulated different ROI sizes, which were eroded from 100% to approximately 50%, and observed that the normalized absolute average deviation and error increased with decreased ROI. Using our method, more objective, concrete, and accurate data could be obtained by including the whole-body phantom (whole poor uniformity area).

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p

Background/aim Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. Patients and methods PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. Results Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. Conclusion The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample.

Graft biopsy is the gold standard for diagnosis of BK polyomavirus-associated nephropathy (BKPyVAN), and polymerase chain reaction is the most specific screening technique. Development of a noninvasive, cost-effective marker for BKPyVAN is important.We reviewed 492 adult kidney transplant patients. We investigated peripheral blood lymphocyte (PBL) count and urinary cytology at graft biopsy in patients with BKVPyAN (n = 21), acute T-cell-mediated rejection (n = 79), and no evidence of acute rejection (n = 149). We performed univariate and multivariate logistic regression and receiver operating characteristics analyses to compare the test performance of PBL count, urinary cytology, and their combination for diagnosis of BKPyVAN.The PBL count at biopsy was significantly lower in the BKPyVAN group than the acute T-cell-mediated rejection and no acute rejection groups (959 ± 290/μL, 1433 ± 673/μL, and 1531 ± 549/μL, respectively; P .01). The PBL count was 959 ± 290/μL at diagnosis of BKPyVAN and increased to 1123 ± 377/μL, 1238 ± 419/μL, and 1292 ± 491/μL at 1, 2, and 3 months after treatment, respectively (P .05). On univariate analysis, the area under the curve was significantly higher for the combined model than for PBL and cytology alone (0.930, 0.797, and 0.875, respectively; P .01). The improved test performance in the combined model remained significant after multivariate adjustment (0.972, 0.844, and 0.928, respectively; P .01).Decreased PBL count was found in BKPyVAN, and the predictive performance of the combination of PBL count and urinary cytology was significantly enhanced for diagnosis of BKPyVAN.

Although the postoperative recurrence rate for pancreatic neuroendocrine tumors (PNETs) is reported to be 13.5%‐30%, the paucity of valuable biomarkers to predict recurrence poses a problem for the early detection of relapse. Hence, this study aimed to identify new biomarkers to predict the recurrence of PNETs. We performed RNA sequencing (RNA‐Seq) on RNA isolated from frozen primary tumors sampled from all localized G1/G2 PNETs resected curatively from 1998 to 2015 in our institution. We calculated differentially expressed genes (DEGs) in tumor with and without recurrence (≥3 years) for the propensity‐matched cohort. Gene ontology analysis for the identified DEGs was also performed. Furthermore, we evaluated the expression levels of candidate genes as recurrence predictors via immunostaining. Comparison of transcriptional levels in tumors with and without recurrence identified 166 DEGs. Up‐ and downregulated genes with high significance in these tumors were mainly related to extracellular organization and cell adhesion, respectively. We observed the top three upregulated genes, C‐type lectin domain family 3 member A (CLEC3A), matrix metalloproteinase‐7 (MMP7), and lipocalin2 (LCN2) immunohistochemically and compared their levels in recurrent and nonrecurrent tumors. Significantly higher recurrence rate was shown in patients with positive expression of CLEC3A (P = 0.028), MMP7 (P = 0.003), and LCN2 (P = 0.040) than that with negative expression. We identified CLEC3A, MMP7, and LCN2 known to be associated with the phosphatidylinositol‐3‐kinase/Akt pathway, as potential novel markers to predict the postoperative recurrence of PNETs.

The interaction between post-transplant anemia (PTA) and allograft function in kidney transplantation has not been evaluated directly. PTA, defined by WHO/AST criteria, was investigated in 1307 adult kidney transplant recipients between 2000 and 2015 (median follow-up, 7 years). We investigated the impact of hemoglobin (Hb) on graft failure (non-censored for death) and their interactions, time-dependent Cox model, and subgroup analysis were used. PTA prevalence was 43.6% at 7 years and varied according to allograft function, recipient sex, and follow-up period. Decreased Hb considering the time-varying effect was associated with an increased risk of graft failure (hazard ratio = 1.83, 95% CI 1.66–2.02, P

Purpose This study aimed to develop a novel technique for retrospective distortion correction based on non-rigid image registration in magnetic resonance diffusion image. Methods A 3.0 T MRI scanner with an 18-channel dedicated breast coil and the outer shell of the original breast phantom, which provided images with non-uniform fat-suppression based on clinical data were used. The diffusion-weighted imaging with and without parallel imaging (PI) was used. The proposed study included several steps, which are FOV size matching, matrix size matching, image segmentation, edge detection, non-rigid image registration, and image wrap. We compared the results obtained using the proposed method with that obtained using TOPUP images. The correlation was assessed between T1-weighted image with fat suppression (FS-T1WI) and b1000 image with the help of cross-correlation coefficient (CCC). Shape-error analysis of tumor model and apparent diffusion coefficient (ADC) was calculated. The Steel–Dwass multiple-comparison tests were used for all comparisons and statistical analysis (P Results The novel method of CCC showed the highest correlation between FS-T1WI and b1000 images. In the Steel–Dwass multiple-comparison test, significant differences were found (P The novel method was the lowest degree of error. With PI in the right breast, no significant differences, whereas in the left breast, significant differences were observed except for between novel method and TOPUP (P = 0.73). Without PI in the right breast, significant differences were observed. In the left breast, no significant differences were observed between any combinations. The ADC value, no significant differences were observed for non-correction and novel methods. Conclusions We developed a novel technique for retrospective distortion correction based on non-rigid image registration. The high degree of accuracy of this method combined with the lack of requirement for additional scans renders it a promising tool for application in clinical practice.

Although minimally invasive procedures have been established as the standard for a donor nephrectomy, there are many different surgical techniques described in the literature. The aim of this study is to compare the outcomes of kidney transplant procedures using the pure retroperitoneoscopic donor nephrectomy (PRDN) and hand-assisted retroperitoneoscopic donor nephrectomy (HARDN) techniques. A retrospective study involving 1508 transplant procedures was conducted; 874 were PRDN procedures; and 634 were HARDN. We reviewed the outcomes of the PRDN and HARDN groups, which were performed at two different centers over an identical time period. Donors in the PRDN group had a longer operation time (P

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by cystic dilation of the pancreatic duct, caused by mucin hypersecretion, with slow progression via the adenoma-carcinoma sequence mechanism. Mutation of GNAS at codon 201 is found exclusively in IPMNs, occurring at a rate of 41-75%. Recent advances in molecular biological techniques have demonstrated that GNAS mutation might play a role in the transformation of IPMNs after the appearance of neoplastic cells, rather than in the tumorigenesis of IPMNs. GNAS mutation is observed frequently in the intestinal subtype of IPMNs with MUC2 expression, and less frequently in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC). Research has focused on assessing GNAS mutation status in clinical practice using various samples. In this review, we discuss the clinical application of GNAS mutation assessment to differentiate invasive IPMNs from concomitant PDAC, examine the clonality of recurrent IPMNs in the remnant pancreas using resected specimens, and differentiate pancreatic cystic lesions using cystic fluid collected by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), duodenal fluid, and serum liquid biopsy samples.

Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients’ prognosis and facilitates surgical procedures.