[Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet].

Objective To study the expression of SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4(SMARCA4)/Brahma-related gene 1,V-raf murine sarcoma viral oncogene homolog B(BRAF),P53,programmed cell death protein-1(PD-1),and programmed death-ligand 1(PD-L1),and changes in the expression of BRAF and neurotrophic tyrosine receptor kinase(NTRK) in the patients with colorectal cancer in Tibet,thereby providing a basis for targeted therapy and immunotherapy for this disease in Tibet. Methods A total of 64 patients with colorectal cancer resected in the Tibet Autonomous Region People's Hospital from January 2015 to July 2021 were enrolled in this study.The expression of SMARCA4,BRAF,P53,PD-1,and PD-L1 was detected by immunohistochemical staining.The gene fusion involving NTRK1,NTRK2,and NTRK3 was detected by fluorescence in situ hybridization,and the BRAF V600E gene mutation by polymerase chain reaction. Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.

A puzzling case report of well-differentiated neuroendocrine tumor mixed with gastric adenocarcinoma of the fundic gland type associated with autoimmune gastritis.

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a rare gastric neoplasm. We present a unique case of multiple GA-FG that coexisted with the well-differentiated neuroendocrine tumors in a patient with autoimmune gastritis. To our knowledge, this is the first documented instance of such a co-occurrence and the molecular mechanism of their origin has been reviewed systematically. A 47-year-old male presented to our hospital with abdominal distension for over 10 years. Gastroscopy revealed multiple gastric eminence lesions (0.2-1.5 cm). After endoscopic mucosal resection, the pathological morphology showed mixed tumor components infiltrating into the submucosa with puzzling similarity. One with uniform-sized tumor cells arranged in nests or tubes and the other a well-differentiated tubular adenocarcinoma with irregular branching and visible gland fusion. Immunohistochemistry findings revealed the first component expressed typical markers of neuroendocrine tumor, whereas the second component expressed pepsinogen and mucin-6, indicating the presence of oxyntic gland adenocarcinoma. Due to the tumors' proximity to the surgical margins, the patient underwent laparoscopic subtotal gastrectomy three months after the diagnosis without any tumor residue and showed no recurrence or metastasis occurred in the following regular checkups.

EGFR mediates epithelial­mesenchymal transition through the Akt/GSK-3ß/Snail signaling pathway to promote liver cancer proliferation and migration.

Epidermal growth factor receptor (EGFR) is expressed in various types of cancer and is associated with the malignant biological behavior of cancer cells. In the present study, the expression of EGFR in hepatocellular carcinoma (HCC) tissues and liver cancer cells was detected by immunohistochemical staining, western blotting and immunofluorescence. Furthermore, a lentivirus was transduced into HepG2 liver cancer cells to knock down EGFR expression. Cell proliferation and migration, and the expression levels of epithelial-mesenchymal transition (EMT) markers were assessed by EdU staining, Cell Counting Kit-8, colony formation, wound healing and Transwell assays, and western blotting. The results revealed that EGF/EGFR can mediate EMT through the Akt/glycogen synthase kinase-3ß (GSK-3ß)/Snail signaling pathway to promote HepG2 cell proliferation and migration. Inhibition of the activation of the EGFR signaling pathway can help to partially reverse the EMT phenotype, and inhibit the proliferation and migration of HepG2 cells. In conclusion, the EGFR/Akt/GSK-3ß/Snail signaling pathway serves an important role in HCC progression, and inhibition of the activation of the EGFR signaling pathway may be a valuable strategy in liver cancer treatment.

[Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet].

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

[Clinicopathological Features of Meningiomas in Tibet].

Objective To analyze the clinicopathological features and immunohistochemical expression of meningiomas in the Tibetan population in Tibet,and improve the understanding of meningiomas. Methods The clinical and pathological data of all the meningiomas diagnosed by pathology in Tibet Autonomous Region People's Hospital from April 2013 to March 2021 were analyzed retrospectively.All the cases underwent immunohistochemical staining of trimethylation of lysine 27 on histone H3 (H3K27me3),mucin 4 (MUC4),somatostatin receptor 2 (SSTR2),progesterone receptor,epithelial membrane antigen,glial fibrillary acidic protein,vimentin,S-100,P53,and Ki-67.The histopathological features and the staining results were observed under a light microscope. Results A total of 116 cases of meningiomas were included in this study,with the male-to-female ratio of 1.0∶2.6 and the age of 4-73 years.The main clinical symptom was headache.The imaging examination showed that 114 cases had single lesions and 2 cases had multiple lesions.The tumors were located in the cranium (108 cases) and spinal canal (8 cases).The maximum diameter of the tumors ranged from 0.3 cm to 10.0 cm,with a mean of (5.7±2.2) cm.In terms of microscopic grading and histological types,the 116 cases included 111 cases of WHO grade Ⅰ (including 53 cases of fibrous type,20 cases of meningothelial type,24 cases of transitional type,10 cases of psammomatous type,etc.),4 cases of WHO grade Ⅱ (3 cases of atypical type and 1 case of clear cell type),and 1 case of WHO grade Ⅲ (papillary type).The immunohistochemical staining showed H3K27me3 expression absent in 9 cases (9/116,7.8%),MUC4 positive in 64 cases (64/116,55.2%),SSTR2 positive in 101 cases (101/116,87.1%).Eighty cases had follow-up results,among which 71 cases had no recurrence,while 9 cases recurred. Conclusions Meningioma is the most common tumor in the central nervous system in the pathological file of Tibet.It mainly attacks the middle-aged female patients,occupying the parasagittal sinus,falx,and convex surface of the brain.Fibrous meningioma of WHO grade Ⅰ is common,while the meningiomas of WHO grades Ⅱ and Ⅲ are rare.The expression degree of MUC4 is higher in meningothelial and transitional meningiomas but lower in fibrous meningiomas.There may be no correlation between the absence of H3K27me3 expression and prognosis.

[Primary Cutaneous Anaplastic Large Cell Lymphoma:Report of One Case].

Primary cutaneous anaplastic large cell lymphoma is a rare non-Hodgkin's lymphoma.The tumor cells have the characteristics of anaplastic cells,expressing CD30 but not anaplastic lymphoma kinase.In this study,we reported a case of primary cutaneous anaplastic large cell lymphoma in a Tibetan child and summarized the clinicopathological features,aiming to strengthen the understanding of this disease.

[Retrospective Analysis of Pathological Diagnosis of Central Nervous System Diseases in Tibet].

Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188∶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82∶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106∶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade Ⅰ,3.7%(4/108)cases of grade Ⅱ,and only 1(1/108,0.9%)case of grade Ⅲ.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade Ⅲ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.

[Androgen Insensitivity Syndrome with Bilateral Cryptorchidism and Seminoma in Tibet:Report of One Case].

Androgen insensitivity syndrome(AIS)with bilateral testicular malignant transformation is very rare,and its diagnosis should be based on clinical manifestations,physical examination,serological findings,karyotype analysis,and pathological findings.This study reported a case of complete androgen insensitivity syndrome among Tibetan in Tibet.It took 17 years from the discovery of congenital absence of uterus to bilateral pelvic mass resection.Pathological examination confirmed that bilateral pelvic space occupying lesions were dysplastic testicular tissue with seminoma and sertoli cell adenoma-like nodules.This study summarized the clinicopathological features to deepen the understanding of the disease.

Global supply chains in the pandemic.

We study the role of global supply chains in the impact of the Covid-19 pandemic on GDP growth using a multi-sector quantitative framework implemented on 64 countries. We discipline the labor supply shock across sectors and countries using the fraction of work in the sector that can be done from home, interacted with the stringency with which countries imposed lockdown measures. One quarter of the total model-implied real GDP decline is due to transmission through global supply chains. However, "renationalization" of global supply chains does not in general make countries more resilient to pandemic-induced contractions in labor supply. This is because eliminating reliance on foreign inputs increases reliance on the domestic inputs, which are also disrupted due to nationwide lockdowns. In fact, trade can insulate a country imposing a stringent lockdown from the pandemic-shock, as its foreign inputs are less disrupted than its domestic ones. Finally, unilateral lifting of the lockdowns in the largest economies can contribute as much as 2.5% to GDP growth in some of their smaller trade partners.

[Clinicopathological Features and Expression of P504s,E-cadherin,Erythroblast Transformation-specific Related Gene and Estrogen Receptor in Prostate Adenocarcinoma in Tibet].

Objective To investigate the clinicopathological features and immunohistochemical expression of P504s,E-cadherin,erythroblast transformation-specific related gene(ERG)and estrogen receptor(ER)in prostate adenocarcinoma in Tibet.Methods The clinical data of 15 patients with prostate adenocarcinoma diagnosed by the Department of Pathology of Tibet Autonomous Region People's Hospital from September 2013 to September 2020 were analyzed retrospectively.All patients were assigned to prognostic grade groups based on Gleason score according to the WHO 2016 criteria.Immunostaining of P504s,E-cadherin,ERG,and ER was performed.Results The age of all 15 patients ranged from 61 to 86 years.The serum prostate specific antigen(PSA)concentration was ≥20 ng/ml in 12 patients and<20 ng/ml in 3 patients.Among the 15 patients,11 underwent needle biopsy,1 transurethral resection of the prostate,and 3 radical prostatectomy.Prognostic grouping results revealed 5 cases in grade groups 1-3,4 cases in grade group 4,and 6 cases in grade group 5.Immunohistochemistrically,15 cases(100%)were positive for P504s,E-cadherin and PSA;one case(7%)was positive for ERG;all cases were negative for P63,ER and CK34ßE12.Thirteen cases were followed up for 2-48 months,with 2 cases treated with total prostatectomy and 11 cases with non-surgical treatment.Two cases were lost to follow-up. Conclusions Prostate adenocarcinoma is rare relatively in Tibet.The accuracy of diagnosis can be improved by using multiple immunohistochemical markers.The cases of grades 4 and 5 by pathological confirmed are relatively common in Tibet.P504s and E-cadherin are highly expressed in prostate adenocarcinoma patients in Tibet,while ERG presents low expression,ER is unexpressed.

Development of a Sandwich Chemiluminescence Immunoassay for the Detection of Intact Procollagen Type I N Propeptide with Magnetic Nanosphere Carrier Technology.

The metabolic product of type I collagen synthesis, intact procollagen type I N propeptide (intact PINP), is a potential marker of bone formation and osteoporosis, which is not affected by kidney function. We sought to establish a chemiluminescent immunoassay method for the detection of serum intact PINP with previously prepared paired monoclonal antibodies and to evaluate the diagnostic value of the assay in osteoporosis. Using the capture molecule and monoclonal antibody as detection molecule, a diagnostic reagent was developed to detect intact PINP in serum with magnetic nanosphere carriers by the chemiluminescence method, and its analytical performance in the laboratory was evaluated. Serum intact PINP was measured in 142 healthy people and 115 osteoporosis patients. Results were matched with results of a similar test kit, Roche total PINP Elecsys Chemiluminescent Immunoassay Assay. Compared with the performance of the Roche PINP assay product, our method had higher sensitivity (0.02 ng/mL), wider linear range (0.02-1500 ng/mL), and anti-interference. Serum intact PINP values in osteoporosis patients were significantly higher than in healthy subjects (p < 0.001). Our method had good consistency compared with the Roche PINP assay (r = 0.9794). This chemiluminescence method for detecting serum intact PINP (CLIA-intact PINP) with magnetic nanosphere carrier technology meets the requirements of a clinical testing reagent and is expected to have clinical application after further evaluation and can compete with expensive imported kits on the market.

Development of chemiluminescence method based on serum type I collagen hydroxyl terminal peptide ß special sequence (ß-CTX).

The objective of this work is to develop and verify the analytical performance of a chemiluminescence immunoassay for the specific sequence ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX) in human serum. Two specific monoclonal antibodies (mAb-8A03 and mAb-3D12) with high affinity for ß-CTX were selected, and, under optimized conditions, a chemiluminescence immunoassay method (CLIA) for ß-CTX was established. The CLIA of ß-CTX detected ß-CTX in a wide range of 2.0-6000 ng/L. The recovery rate in serum is 95-105%, the specificity is high, and the cross-reaction rate with common easily interfering substances is low (not more than 0.01%). The CLIA correlates well with Roche electrochemiluminescence immunoassay (ECLIA), with a correlation coefficient of 0.9551, which fully meets the requirements of clinical analysis. The developed ß-CTX CLIA kit has high sensitivity and good stability. It has the same performance as the commercial Roche ECLIA kit and can be applied clinically.

Clinical features and management experience in patients with metastatic spinal bladder cancer: a single-institution 10-year retrospective study.

BACKGROUND: Limited case reports of metastatic spinal bladder cancer (MSBC) have been published to date. Owing to the rarity of this condition, it has not been well-studied and it is thus difficult to predict patient prognosis or to plan appropriate clinical treatment strategies for MSBC. This study is by far the largest clinical case series on MSBC worldwide. METHODS: Six patients with MSBC were included from January 2010 to May 2020 at the bone tumor center of orthopedics department in Peking Union Medical College Hospital. Clinical information, radiological data, operative notes, and pathological results of all patients were reviewed. Baseline clinical data of all patients were retrospectively analyzed, and regular follow-up was performed postoperatively. Overall survival (OS) was the time from the initial spinal surgery to the death of patients or the end of May 2020, whichever came first. RESULTS: All six patients with MSBC were male patients, with an average age of 68.1±12.8 years. The mean interval between surgery for primary BC and the first discovery of spinal metastases was 15.6 [2-33] months. Overall, nine spinal operations were performed in the six patients. The mean follow-up period was 11.0±4.2 (range, 7-18) months. All patients (100%) died from MSBC during the follow-up period, with a mean OS of 11.0±4.2 (range, 7-18) months. CONCLUSIONS: Patients with MSBC had a poor prognosis in this study. Spinal surgery combined with adjuvant therapy may contribute to relieving the clinical symptoms and improve the quality of life of patients. Appropriate surgical treatment options should be selected according to patients' general condition and relevant characteristics of spinal metastases.

Targeted Delivery of Glypican 3 (GPC3) Antibody-Modified MicroRNA (miR let-7b-5p) Polymer Nanoparticles to Sorafenib-Resistant Hepatsocellular Carcinoma Cells.

The miR let-7b-5p (a kind of microRNAs) has many pathophysiological regulation effects, including human hepatocellular carcinoma (HCC) pathogenesis. This study investigated whether nanoparticle-mediated miR let-7b-5p could jointly enhance the therapeutic effect of sorafenib on HCC by inhibiting the proliferation of HCC cells, inducing apoptosis, and reversing drug resistance. We evaluated the level of miR let-7b-5p in sorafenib-resistant HepG2 cells (HepG2R) and HepG2 HCC cells by qRT-PCR and analyzed the biological effects of hepatocellular carcinoma treated with sorafenib with miR let-7b-5p, and further studied the toxicity of nanoparticles (Ab-miR-NPs) that deliver miR let-7b-5p mimics and target GPC3 on the surface of hepatocellular carcinoma cells. Results showed that, in HepG2 cells, the expression level of miR let-7b-5p was significantly higher than that in HepG2R cells. Targeted nanoparticle Ab-miR-NPs mediated the delivery of miR let-7b-5p to the HCC cytoplasm and released miRNA after being broken down, down-regulating the expression of IGF1R and inhibiting AKT/mTOR and Ras/Raf signal transmission. Ab-miR-NPs not only enhanced the proliferation of sorafenib in cultured HepG2R cells and induced cell apoptosis efficiency, but they also improved the anti-tumor activity in the mouse models. These results indicated that GPC3 antibody-modified PLGA-PLL (polylactic acid-glycolic acetic copolymer grafted hyper-branched polylysine) loaded miR let-7b-5p polymer nanoparticles combined with sorafenib may be a new treatment strategy for HCC resistant to sorafenib.

[Clinicopathological Analysis of Brain Metastatic Carcinoma in Tibet].

Objective To investigate the clinicopathological features and immunohistochemical phenotypes of brain metastatic carcinoma in Tibetan patients. Methods The clinical and pathological data of all patients with brain metastases from 2014 to 2020 in Tibet Autonomous Region People's Hospital were retrospectively analyzed,including 13 cases of brain metastatic carcinoma.All cases were diagnosed and classified by immunohistochemical staining. Results 13 cases(9 males and 4 females)of brain metastatic carcinoma,aged 26-62 years old,present with headache,dizziness,nausea and vomiting clinically.Four patients had a medical history of tumor,and among the 9 patients with no history of tumor,7 present space occupying lesions in both the brain and other organs.Imaging data could be found in 10 cases,including 4 cases of single lesion and 6 cases of multiple lesions.Primary tumors were identified in 11 cases(8 located in the lung,including 4 cases of adenocarcinoma,3 cases of small cell carcinoma,and 1 case of squamous cell carcinoma;1 case of urothelial carcinoma of the renal pelvis;1 case of thyroid papillary carcinoma;1 case of uterine choriocarcinoma),whereas the primary tumor was unknown for the other 2 cases(1 case of small cell carcinoma and 1 case of adenocarcinoma). Conclusions Brain metastatic carcinoma are more common among middle-aged and elderly people in Tibet.Most of the cases have no history of tumor,with the initial site at the brain metastatic lesions.The most common primary site is the lung,and the primary site of some cases is unknown.Multiple lesions are common in brain metastatic carcinoma,especially in the cerebral hemisphere.For older patients with multiple brain space occupying lesions,the possibility of brain metastatic carcinoma increases.

Learning Curve From 450 Cases of Robot-Assisted Pancreaticoduocectomy in a High-Volume Pancreatic Center: Optimization of Operative Procedure and a Retrospective Study.

OBJECTIVE: We aimed to describe our experience and the learning curve of 450 cases of robot-assisted pancreaticoduodenectomy (RPD) and optimize the surgical process so that our findings can be useful for surgeons starting to perform RPD. SUMMARY BACKGROUND DATA: Robotic surgical systems were first introduced 20 years ago. Pancreaticoduodenectomy (PD) is a challenging surgery because of its technical difficulty. RPD may overcome some of these difficulties. METHODS: The medical records of 450 patients who underwent RPD between May 2010 and December 2018 at the Shanghai Ruijin Hospital were retrospectively analyzed. Operative times and estimated blood loss (EBL) were analyzed and the learning curve was determined. A cumulative sum (CUSUM) analysis was used to identify the inflexion points. Other postoperative outcomes, postoperative complications, and long-term follow-up were also analyzed. RESULTS: Operative time improved graduallyovertimefrom405.4 ±â€Š112.9 minutes (case 1-50) to 273.6 ±â€Š70 minutes (case 301-350) (P < 0.001). EBL improved from 410 ±â€Š563.5 mL (case 1-50) to 149.0 ±â€Š103.3 mL (case 351-400) (P< 0.001). According to the CUSUM curve, there were 3 phases in the RPD learning curve. The inflexion points were around cases 100 and 250. The incidence of pancreatic leak in the last 350 cases was significantly lower than that in the first 100 cases (30.0% vs 15.1%, P = 0.003). CONCLUSIONS: RPD is safe and feasible for selected patients. Operative and oncologic outcomes were much improved after experience of 250 cases. Our optimization of the surgical process may have also contributed to this. Future prospective and randomized studies are needed to confirm our results.

Oncological outcomes of robotic-assisted versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: Robotic-assisted minimally invasive surgery is associated with worse oncologic outcomes for some but not other types of cancers. We conducted a propensity score-matched analysis to compare oncologic outcomes of robotic-assisted laparoscopic (RPD) vs. open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Treatment-naïve PDAC patients undergoing either RPD or OPD at our hospital between January 2013 and December 2017 were included. Propensity score matching was conducted at a ratio of 1:2. The primary outcome was disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 672 cases were identified. The propensity score-matched cohort included 105 patients receiving RPD and 210 patients receiving OPD. The 2 groups did not differ in the number of retrieved lymph nodes [11 (7-16) vs. 11 (6-17), P = 0.622] and R0 resection rate (88.6% vs. 89.0%, P = 0.899). There was no statistically significant difference in median DFS (14 [95% CI 11-22] vs. 12 [95% CI 10-14] months (HR 0.94; 95% CI 0.87-1.50; log-rank P = 0.345) and median OS (27 [95% CI 22-35] vs. 20 [95% CI 18-24] months (HR 0.77; 95% CI 0.57-1.04; log-rank P = 0.087) between the two groups. Multivariate COX analysis showed that RPD was not an independent predictor of DFS (HR 0.90; 95% CI 0.68-1.19, P = 0.456) or OS (HR 0.77; 95% CI 0.57-1.05, P = 0.094). CONCLUSION: Comparable DFS and OS were observed between patients receiving RPD and OPD. This preliminary finding requires further confirmation with prospective randomized controlled trials.

Robotic-assisted versus open distal pancreatectomy for benign and low-grade malignant pancreatic tumors: a propensity score-matched study.

BACKGROUND: This study aimed to compare the short-term outcomes of open and robotic-assisted distal pancreatectomy (ODP and RDP) for benign and low-grade malignant tumors. METHODS: The patients who underwent RDP and ODP for benign or low-grade malignant pancreatic tumors at our center were included. After PSM at a 1:1 ratio, the perioperative variations in the two cohorts were compared. RESULTS: After 1:1 PSM, 219 cases of RDP and ODP were recorded. The RDP cohort showed advantages in the operative duration [120 (90-150) min vs 175 (130-210) min, P < 0.001], estimated blood loss [50 (30-175) ml vs 200 (100-300) ml, P < 0.001], spleen preservation rate (63.5% vs 26.5%, P < 0.001), infection rate (4.6% vs 12.3%, P = 0.006), and gastrointestinal function recovery [3 (2-4) vs. 3 (3-5), P = 0.019]. There were no significant differences in postoperative pancreatic fistula, postoperative hemorrhage, and delayed gastric emptying. Multivariate analysis showed that RDP (HR 0.24; 95% CI 0.16-0.36, P < 0.001), age (HR 1.02; 95% CI 1.00-1.03, P = 0.033), tumor size (HR 1.28; 95% CI 1.17-1.40, P < 0.001), pathological inflammatory neoplasm type (HR 5.12; 95% CI 2.22-11.81, P < 0.001), and estimated blood loss (HR 1.003; 95% CI 1.001-1.004, P < 0.001) were independent predictors of spleen preservation; RDP (HR 0.27; 95% CI 0.17-0.43, P < 0.001), age (HR 1.02; 95% CI 1.00-1.03, P = 0.022), elevated CA 19-9 level (HR 2.55; 95% CI 1.02-6.39, P = 0.046), tumor size (HR 1.44; 95% CI 1.29-1.61, P < 0.001), pathological inflammatory neoplasm type (HR 4.48; 95% CI 1.69-11.85, P = 0.003), and estimated blood loss (HR 1.003; 95% CI 1.001-1.004, P < 0.001) were independent predictors of spleen preservation with the Kimura technique. CONCLUSION: RDP has advantages in the operative time, blood loss, spleen preservation, infection rate, and gastrointestinal function recovery over ODP in treating benign and low-grade malignant pancreatic tumors. The robotic-assisted approach was an independent predictor of spleen preservation and use of the Kimura technique.