Learning curve stratified outcomes after robotic pancreatoduodenectomy: International multicenter experience.

BACKGROUND: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking. METHODS: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points. RESULTS: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually. CONCLUSION: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach.

The value of dual probes in tracerpositron emission tomography/magnetic resonance imaging in the grading diagnosis of pancreatic neuroendocrine neoplasms / 中华消化杂志

Objective:To explore the diagnostic and grading value of combination of 68Ga -1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide ( 68Ga-DOTA-TATE) and 18F-flurodeoxyglucose ( 18F-FDG) dual probes in multi-parameter positron emission tomography (PET)/magnetic resonance (MR) imaging in pancreatic neuroendocrine neoplasm (PNEN). Methods:From April 9th, 2020 to February 24th, 2022, in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the clinical data and the imaging of 68Ga-DOTA-TATE PET/MR and 18F-FDG PET/MR of 59 patients with pancreatic tumors (27 male, 32 female, aged 22 to 75 years old(51.8±13.3) years old), confirmed by surgical or biopsy pathology were retrospectively analyzed. All the cases were divided into PNEN group (42 cases) and non-PNEN group (17 cases) according to pathological results. Among which 39 patients with PNET were further divided into grade 1 group (G1 group, 27 cases) and grade 2 group (G2 group, 12 cases). Non-zero parameters were selected via the least absolute shrinkage and selection operator (LASSO) regression approach, and a logistic regression model was established by combination of the selected features and the corresponding non-zero coefficients. The measurement data with non-normal distribution were compared by Mann-Whitney U test. The receiver operating characteristic (ROC) curve were used to detemine the optimal cut off value to assess the dignostic efficiency. Results:Compared with those of non-PNEN group, the parameters of PNEN group increased, which included maximum standard uptake value of 68Ga-DOTA-TATE(SUV Gmax, 46.70 (22.37, 76.35) vs. 7.12 (4.75, 8.64)), mean standard uptake value of 68Ga-DOTA-TATE(SUV Gmean, 25.50 (13.18, 43.90) vs. 3.65 (2.89, 4.69)), peak standard uptake value of 68Ga-DOTA-TATE (SUV Gpeak, 27.17 (12.39, 46.97) vs. 5.46 (4.12, 6.56)), total lesion somatostatin receptor (SSR) expression (TLSRE, 68.21 (32.52, 440.96) vs. 26.02 (14.87, 69.57)), SUV Gmax/maximum standard uptake value of 18F-FDG (SUV Fmax, 12.71 (3.80, 21.70) vs. 1.10 (0.52, 2.35)), tumor to background ratio of 68Ga-DOTA-TATE (TBR G, 13.31 (5.54, 22.38) vs. 1.57 (1.31, 2.66)), tumor to liver ratio of 68Ga-DOTA-TATE(T/L G, 6.54 (2.90, 9.63) vs. 0.74 (0.65, 0.94)), tumor to spleen ratio of 68Ga-DOTA-TATE (T/S G, 2.36 (0.97, 3.70) vs. 0.25 (0.23, 0.38)), tumor to mediastinum ratio of 68Ga-DOTA-TATE (T/M G, 104.41 (34.03, 206.52) vs. 16.00 (12.87, 21.46)), SUV Gmax/minimum apparent diffusion coeffecient (ADC min, 55.14 (22.50, 96.37) vs. 6.76 (4.39, 12.76)) and SUV Gmean/ADC min (34.57 (13.47, 55.13) vs. 3.57 (2.46, 6.81)), and the differences were statistically significant ( U=28.00, 25.00, 32.00, 198.00, 54.00, 31.00, 28.00, 19.00, 10.00, 56.00 and 44.00, all P<0.01). The area under the curve (AUC) and diagnostic accuracy of dual-probe PET/MR imaging in the diagnosis of PNEN and non-PNEN were 0.941 and 96.6%, respectively. The AUC and diagnostic accuracy of model Y 1 in the diagnosis of PNEN and non-PNEN were 0.959 and 96.6%, respectively. There was no significant difference in AUC between model Y 1 and dual-probe PET/MR imaging in PNEN diagnosis ( P>0.05), however combining model Y 1 could improve the accuracy of PNEN diagnosis (100.0%). Compared with those of PNET G1 group, the parameters of G2 Group were higher, which included the maximum diameter of tumor (2.69 cm (2.08 cm, 5.00 cm) vs. 1.50 cm (1.20 cm, 2.50 cm)), metabolic tumor volume (MTV, 7.56 mL (4.45 mL, 53.57 mL) vs. 2.16 mL (1.22 mL, 5.48 mL)), total lesion glycolysis (TLG, 22.24 (11.95, 189.85) vs. 3.81 (2.11, 18.67)), tumor to background ratio of 18F-FDG (TBR F, 2.94 (2.00, 3.96) vs. 1.48 (1.29, 3.72)), tumor to liver ratio of 18F-FDG (T/L F, 2.32 (1.35, 2.98) vs. 1.08 (0.90, 2.17)) and SSR-expressing tumor volume (SRETV, 8.00 (3.06, 40.00) vs. 1.91 (0.95, 4.88)), and the differences were statistically significant ( U=66.00、66.00、77.00、93.00、90.00、65.50, all P<0.05). The maximum diameter of tumor was the best single parameter for the differential diagnosis of PNET G2 and G1, AUC was 0.796 and the cutoff value was 1.90 cm. The model Y 2, which combined the maximum diameter of tumor and TBR G had an AUC of 0.835 for the differential diagnosis of PNET G2 and G1. There was no significant difference in AUC between the maximum diameter of tumor and model Y 2 ( P>0.05). However the combination of the maximum diameter of tumor and model Y 2 could improve the accuracy of differential diagnosis of PNET G2 and G1 (94.87%). Conclusion:The combination of multi-parameter of 68Ga-DOTA-TATE and dual-probe 18F-FDG PET/MR imaging can improve the diagnostic and grading accuracy of PNEN, which may be helpful in the selection of clinical treatment for patients.

Up-regulation of Toll-like receptors 2 and 4 on peripheral monocytes after major abdominal surgical operation.

BACKGROUND: This study is to investigate the time-course expression of TLR2 and TLR4 on peripheral monocytes in patients receiving major abdominal surgical operation. METHODS: Blood samples were obtained from peripheral vein before and after an operation in 30 patients with gastrointestinal or pancreatic surgery. The mRNA expression of TLR2, TLR4, TNF-α and IL-6 on peripheral blood mononuclear cells (PBMC) was analyzed by real-time PCR. The expressions of TLR2, TLR4, HLA-DR, CD80, and CD86 on monocytes were analyzed by flow cytometry. The expressions of TLR2 and TLR4 on monocytes responding to each agonist (zymosan and lipopolysaccharide) were also measured by flow cytometry. RESULTS: TLR2 and TLR4 mRNA showed significant up-regulation after the completion of the operation when compared with those before the operation. TLR2 expression reached its peak level on day 1 and TLR4 on days 1 and 3. There was no significant difference between pre- and post-operation in the expressions of HLA-DR, CD80 and CD86. Stimulation with zymosan, increased the expression of TLR2 significantly after the operation and reached its highest value on day 3. Similarly, after stimulation with lipopolysaccharide, the expression of TLR4 was also increased and the highest level was observed on day 1. The expression of TNF-α and IL-6 mRNA decreased after completion of the operation and gradually returned to basal level. CONCLUSIONS: The expressions of TLR2 and TLR4 on monocytes were up-regulated during the early period after a major abdominal surgical operation in patients, which might be related to the activation of innate immunity.

The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility.

BACKGROUND: Toll-like receptors (TLR) are key innate immunity receptors participating in an immune response. Growing evidence suggests that mutations of TLR2/TLR9 gene are associated with the progress of cancers. The present study aimed to investigate the temporal relationship of single nucleotide polymorphisms (SNP) of TLR2/TLR9 and the risk of hepatocellular carcinoma (HCC). METHODS: In this single center-based case-control study, SNaPshot method was used to genotype sequence variants of TLR2 and TLR9 in 211 patients with HCC and 232 subjects as controls. RESULTS: Two synonymous SNPs in the exon of TLR2 were closely associated with risk of HCC. Compared with those carrying wild-type homozygous genotypes (T/T), risk of HCC decreased significantly in individuals carrying the heterozygous genotypes (C/T) of the rs3804099 (adjusted odds ratio (OR), 0.493, 95% CI 0.331 - 0.736, P < 0.01) and rs3804100 (adjusted OR, 0.509, 95% CI 0.342 - 0.759, P < 0.01). There was no significant association found in two TLR9 SNPs concerning the risk of HCC. The haplotype TT for TLR2 was associated significantly with the decreased risk of HCC (OR 0.524, 95% CI 0.394 - 0.697, P = 0.000). Inversely, the risk of HCC increased significantly in patients with the haplotype CC (OR 2.743, 95% CI 1.915 - 3.930, P = 0.000). CONCLUSIONS: These results suggested that TLR2 rs3804099 C/T and rs3804100 C/T polymorphisms were closely associated with HCC. In addition, the haplotypes composed of these two TLR2 synonymous SNPs have stronger effects on the susceptibility of HCC.

Respiratory impact of paracentesis in cirrhotic patients with acute lung injury.

INTRODUCTION: Ascites may contribute to the loss of lung volume and alter the gas exchange in cirrhotic patients with acute lung injury (ALI). AIM: The aim of the study was to evaluate the effects of paracentesis on respiratory parameters in ventilated cirrhotic patients with ALI. STUDY DESIGN: This was a prospective trial in an intensive care unit of a university hospital. PATIENTS AND METHODS: Thirty-one cirrhotic patients on mechanical ventilation (with ALI) requiring paracentesis were included in this study. Arterial blood gases, intraabdominal pressures, ventilator parameters, and lung volumes were measured before and after the ascitic drainage. RESULTS: Following paracentesis, the intraabdominal pressure decreased (24.1 ± 7.0 vs 12.3 ± 8.9 mm Hg, P < .0001) and the Pao(2)/Fio(2) improved significantly (190.0 ± 65.2 vs 284.9 ± 76.1 mm Hg, P < .0001), without hemodynamic disturbances. End-expiratory lung volume, markedly reduced before drainage, increased significantly following paracentesis (Δ end-expiratory lung volume: +463 ± 249 mL, P = .0009). No adverse effects related to the paracentesis were encountered. CONCLUSION: In contrast to ventilatory recruitment maneuvers, paracentesis is a simple and well-tolerated technique able to improve oxygenation and alveolar recruitment without the risk of the lung overdistension in severely hypoxemic cirrhotic patients.

Pathological characteristics of the solid pseudopapillary tumor of pancreas / 中华胰腺病杂志

Objective To summarize and analyze the pathological characteristics of solid pseudopapillary tumor of pancreas (SPTs).Methods The clinical data of 51 cases of SPTs were retrospectively analyzed.The immunohistochemical localizations of different markers (HSE,SYN,CD_(56),CD_(10),Nestin,Vim,a1-ACT,EMA,AE1/AE3 and CK19) on 39 SPTs were studied.Results Pathological features included a combination of solid and cystic components with pseudopapillae formation and degenerative regions without glands.Among the 39 cases of SPTs,the expression rate of NSE was 97.4%,the expression rate of CD_(56),CD_(10) was 84.6%,the expression rate of Nestin and Vim was 64% and 87%,the expression rate of S100 was 79.5%,the expression rate of a1-ACT and a1-AT was 82.1% and 79.5%,while the expression rate of SYN was 12.8%;however there was low expression and weak positive reaction of EMA,AE1/AE3 and CK19.Conclusions The typical pathological characteristics of SPTs may result from gradual degenerative changes induced anoxemia in some SPT's areas.The heterogeneity of SPTs on different antibody markers showed that the SPTs may be originated from pancreatic embryonic stem cells,and result from immature differentiation of the pluripotential stem cells during pancreatic genesis.

The solid-pseudopapillary tumor of pancreas:the clinical characteristics and diagnosis / 中国医师进修杂志

Objective To study the clinical characteristics and diagnosis of the solid-psendopapillary tumor of pancreas (SPT).Methods The clinical data of 40 SPT from January 1996 to January 2008 were retrospectively analyzed. The average age was (32.9 + 13.6 )years. The average clinical course was (8.6±0.1) months.Clinical symptoms usually included distensible pains and secret anguish in abdomen (60.0%).No jaundice appeared in any case.Results The surgical resection was favorable for the treatment of SPT,which had excellent prognosis.No tumor recurrence were found in those following-up patients. Grossly,the cut surface showed areas of solid and papillary tissue,cystic degeneration,hemorrhage,and necrosis.Pathological features included a combination of solid and cystic components with pseudopapillae formation and degenerative regions without glands.Conclusions SPT has its uniquely clinical and pathological characteristics.Its main diagnosed points are helpful for clinical doctors to make timely diagnosis and reduce the rate of misdiagnosis and mistreatment.