[Effectiveness of minimally invasive surgery in the treatment of pancreatic acinar cell carcinoma].

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

[Clinical effect of laparoscopic transcystic drainage combined with common bile duct exploration for the patients with difficult biliary stones].

OBJECTIVE: To explore the feasibility and efficacy of laparoscopic transcystic drainage and common bile duct exploration in the treatment of patients with difficult biliary stones. METHODS: Between April 2020 and December 2021, eighteen patients with difficult biliary stones received laparoscopic transcystic drainage (C-tube technique) and common bile duct exploration. The clinical characteristics and outcomes were retrospectively collected. The safety and effectiveness of laparoscopic transcystic drainage and common bile duct exploration were analyzed. RESULTS: Among the eighteen patients with difficult biliary stones, thirteen patients received traditional laparoscopic transcystic drainage, and the remaining five received modified laparoscopic transcystic drainage. The mean surgical duration were (161±59) min (82-279 min), no bile duct stenosis or residual stone was observed in the patients receiving postoperative cholangiography via C-tube. The maximum volume of C-tube drainage was (500±163) mL/d (180-820 mL/d). Excluding three patients with early dislodgement of C-tube, among the fifteen patients with C-tube maintained, the median time of C-tube removal was 8 d (5-12 d). The duration of hospital stay was (12±3) d (7-21 d) for the 18 patients. Five C-tube related adverse events were observed, all of which occurred in the patients with traditional laparoscopic transcystic drainage, including two abnormal position of the C-tube, and three early dislocation of the C-tube. All the 5 adverse events caused no complications. Only one grade one complication occurred, which was in a patient with modified laparoscopic transcystic drainage. The patient demonstrated transient fever after C-tube removal, but there was no bile in the drainage tube and the subsequent CT examination confirmed no bile leakage. The fever spontaneously relieved with conservative observation, and the patient recovered uneventfully with discharge the next day. All the 18 patients were followed up for 1-20 months (median: 9 months). Normal liver function and no recurrence of stone were detected with ultrasonography or magnetic resonance cholangiopancreatography (MRCP). CONCLUSION: Laparoscopic transcystic drainage combined with common bile duct exploration is safe and feasible in the treatment of patients with difficult biliary stones. The short-term effect is good. Modified laparoscopic transcystic drainage approach may reduce the incidence of C-tube dislocation and bile leak.

[Advances in indocyanine green fluorescence imaging during hepatectomy].

While surgical operation is the preferred treatment for liver malignancies,the postoperative recurrence rate remains high. In the early 21st century,Japanese scientists first reported the use of indocyanine green(ICG) in liver resection. Follow-up studies also found its potential applications such as identifying tumors,determining surgical margins,delineating segmental boundaries,and preventing bile leakage. At present,ICG fluorescence imaging is applied to some types of hepatectomy with excellent effect and is expected to assist in generating surgical strategies for liver malignancies. However,its safety and efficacy still need further studies to evaluate.

[Problems and strategies in clinical application of associating liver partition and portal vein ligation for staged hepatectomy].

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can speed up the regeneration of future liver remnant (FLR) in short period of time, and offer a chance for surgical resection for patients without sufficient FLR. However, ALPPS still remains controversy due to its high perioperative morbidity and mortality, as well as the uncertain long-term oncological benefits. How to solve these problems is the key to ensure the safety of surgery.This article focus on the indication selection, liver function reserve evaluation and timing to perform the second stage surgery, surgical mode evolution and comparison with portal venous embolization/portal venous ligation+two-stage hepatectomy.

[The value of Gd-EOB-DTPA-enhanced MRI in patients with major resection of liver cancer].

Objective: To investigate the value of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and predicting the risk of post-hepatoectomy liver failure in patients with major resection of liver cancer. Methods: A total number of 212 patients were included from June 2016 to June 2019 at Department of General Surgery, Peking University Third Hospital with a retrospectively collected data.All patients underwent Gd-EOB-DTPA-enhanced MRI for diagnosis and preoperative evaluation of liver function.There were 135 males and 77 females, with age of (63.1±10.3) years old (range: 18 to 86 years old) . Relative enhancement ratio (RER) of the region of interest on Gd-EOB-DTPA-enhanced MRI was acquired by two independent researcher and then conducted the comparison of RER among the patients with or without post-hepatoectomy liver failure (PHLF) .Preoperative evaluation demonstrated that 141 cases infected by hepatitis virus, 128 cases with hepatitis B alone and 11 cases with hepatitis C alone, 2 cases had both of hepatitis B and C, and all patients were grade A judged by Child-Pugh score. The relationship between RER and PHLF was evaluated by Pearson correlation analysis and the diagnostic value of RER in predicting PHLF was test by receiver operating characteristic curve. Results: PHLF occurred in 42 patients according to ISGLS standard. Among them, 31 cases had level A liver failure, 9 cases had level B liver failure and 2 had level C failure. There was a significant correlation between RER and overall level of PHLF and RER was also significantly associated with severe B to C level of PHLF (P<0.05) .The further receiver operating characteristics curve analysis showed that the diagnostic accuracy of RER on overall PHLF was 0.818 (sensitivity 72.9%, specificity 83.3%, cut-off value 73.5%, 95%CI: 0.75 to 0.887) and on severe PHLF was 0.924 (sensitivity 97.0%, specificity 90.9%, cut-off value: 61.5%, 95%CI: 0.79 to 0.90) . Conclusion: For patients who planned to undergo major resection of liver cancer, preoperative Gd-EOB-DTPA-enhanced MRI can help with the assessment of liver function and predicting the risk for post-hepatectomy liver failure.

[Effect of an oral nutritional supplementation on nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy: A multi-center prospective randomized control trial].

Objective: To evaluate the effect of oral nutritional supplementation (ONS) on the nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy. Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13003798). A multi-center randomized controlled trial was conducted. Colorectal cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy, and had nutritional risk (nutrition risk screening 2002 score ≥3) when discharge from hospital in six hospitals (Beijing Hospital, Peking University Third Hospital, Guangzhou Nanfang Hospital, Shanghai Xinhua Hospital, Shanghai Ruijin Hospital, and Shanghai The Sixth People's Hospital) from June 2013 to August 2015 were prospectively enrolled. These patients were randomly divided into the ONS group and control group. Patients in the ONS group received dietary guidance and oral nutritional supplements (2092 kJ/day, whole protein enteral nutrition) for 90 days after discharge from hospital, while patients in the control group only received dietary guidance. Anthropometric measurements (body weight, body mass index [BMI], upper arm circumference, gripping power of the dominant hand, triceps skin fold), nutrition-related laboratory tests (hemoglobin, albumin, prealbumin, total cholesterol, triglyceride), gastrointestinal function scores and quality of life (evaluated by EuroQol five dimensions questionnaire) were collected and compared at baseline (at discharge), and at 30-day, 60-day and 90-day after discharge. Results: A total of 90 patients were included into this multi-center study, of whom 5 patients dropped out, 43 patients were assigned to the ONS group and 42 patients to the control group. Compared with baseline, the body weight of patients in the ONS group increased by (1.523±0.525) kg at 60-day and (1.967±0.661) kg at 90-day, which were significantly higher than those of patients in the control group [60-day: (-0.325±0.518) kg, P=0.015; 90-day: (-0.224±0.705) kg, P=0.027, respectively]. A similar pattern was observed for BMI, the ONS group increased by (0.552±0.203) kg/m(2) at 60-day and (0.765±0.205) kg/m(2) at 90-day, which were significantly higher than those of patients in control group [60-day: (-0.067±0.202) kg/m(2), P=0.034; 90-day: (0.022±0.210) kg/m(2), P=0.013]. No significant differences of other anthropometric measurements and nutrition-related laboratory tests were found between the two groups (all P>0.05). Furthermore, there were no significant differences of improvement in gastrointestinal function and quality of life between two groups (all P>0.05). Conclusion: Oral nutritional supplements can improve the body weight and BMI of colorectal cancer patients with nutritional risk receiving postoperative adjuvant chemotherapy, though it does not improve the quality of life.

[Gastroenteropancreatic neuroendocrine tumor microenvironment and related therapy].

Neuroendocrine tumor(NET) is a kind of highly heterogeneous and ubiquitous tumor, frequently localized in the gastrointestinal tract and pancreas. Surgery combined with regional ablation, endocrine therapy,chemotherapy and targeted therapy presents a favorable prognosis when treated with G1 or G2 gastroenteropancreatic neuroendocrine tumor(GEP-NET). However, there are only limited therapeutic strategies for metastatic unresectable tumors and poorly differentiated NEC,which are closely related to the special tumor microenvironment of neuroendocrine tumors.Targeting tumor microenvironment therapy is an important method in current systematic therapy, but till now the knowledge of neuroendocrine tumor microenvironment and its related treatment are limited. This article will specifically introduce the characteristics of tumor microenvironment in GEP-NET from the following aspects: the formation of enrichment vascular supply in TME,the role of tumor stroma,immune cells and cancer associacted fibroblast, and immune checkpoint and future trend of immunotherapy.

[Laparoscopic treatment for incidental gallbladder cancer: a retrospective 10 years study from a single institution].

Objective: To explore the feasibility of laparoscopic treatment for incidental gallbladder cancer(IGBCA) and analyze the factors influencing prognosis. Methods: A retrospective study of 71 patients with IGBCA received laparoscopic treatment at Department of General Surgery, Peking University Third Hospital from January 2007 to December 2016 was conducted,the clinicopathological data and prognosis were analyzed. There were 18 males and 53 females,aged 23 to 81 years. They were divided into two groups based on the presence of intraluminal mass in the gallbladder. Sixty-five of the 71 patients received laparoscopic radical resection, the prognosis of them were compared with 14 patients with open radical resection. Results: Among the 71 patients,65 patients received radical resection,3 patients simple gallbaldder resection and 3 patients palliative resection. Postoperative complications occurred in 6 patients. IGBCA were detected by frozen section in 57 patients,with the accuracy of 96.5%,while the accuracy of T stage is 43.8% in the 48 patients received T stage evaluation during frozen section examination. The T stages based on final pathology were Tis(n=6),T1a(n=5),T1b(n=10),T2(n=46),and T3(n=4).The number of harvested lymph node was 4.7±2.9(range:2-12).There are 14 patients with lymph node metastasis. The 50 patients with intraluminal gallbladder mass include 21 patients with ≤T1b stage and 29 patients with ≥T2 stage, while the 21 patients without intraluminal gallbladder mass are all with ≥T2 stage. The median survival time of the 71 patients was 33 months, with the 5-year cumulative survival rate 67.3%. The 5-year cumulative survival rate is 78.5% for the 65 patients who received radical resection,comparable with those who received open radical resection(P=0.485).Univariate analysis demonstrated that T stage, lymph node metastasis, G grade, lymphovascular invasion, neural invasion, acute cholecystectomy, bile spillage, gallbladder mass and preoperative CA19-9/CEA were the most important prognostic factors(P<0.05). Conclusions: Laparoscopic treatment for IGBCA is feasible, especially for those with intraluminal gallbladder mass. The accuracy of frozen section examination in evaluating T stage is low.

[Comparison of the minimally invasive treatments of laparoscopic and endosopic for common bile duct stones after gastrojejunostomy].

OBJECTIVE: To explore the feasibility and to compare the merits and demerits of laparoscopic and endoscopic approach in removing common bile duct stones in patients with gastrojejunostomy after gastrectomy. METHODS: Between January 2012 and December 2016, 25 patients with common bile duct stones after gastrojejunostomy received laparoscopic or endoscopic treatment in our centers. They were divided into laparoscopic group and endoscopic group based on treatment approaches for common bile duct stones, including 15 patients in laparoscopic group and 10 in endoscopic group. The clinical characteristics and outcomes between the two groups were retrospectively analyzed. RESULTS: Among the 25 patients with gastrojejunostomy, the method of reconstruction was Billroth II in 21 patients and Roux-en-Y in 4 patients. Six patients received laparoscopic or endoscopic treatment during the acute cholangitis state. Among the laparoscopic group, 5 patients with stones more than 1 cm, 7 patients with multiple stones, while in the endoscopic group, 3 patients with stones more than 1 cm and 4 patients with multiple stones. Fourteen patients in the laparoscopic group with coexisting gallbladder stones, and 6 of their common bile duct stones were successfully removed by transcystic approach without T tube drainage. Stone removals were successful in 4 patients of the endoscopic group by a single performance, including 3 patients with single small stone and one patient with multiple small stones. Two patients in the laparoscopic group were converted to open surgery for severe adhesion and one patient in the endoscopic group turned to laparoscopic operation for failing of finding papilla in the Roux-en-Y anastomotic status. The median hospital stays were 12 d and 10 d, respectively in the laparoscopic and endoscopic group. There were 3 patients with postoperative complications, including one patient with paralytic ileus in the laparoscopic group and 2 patients with biliary pancreatitis or bacteremia in the endoscopic group, and all of them recovered uneventfully with conservative treatment. CONCLUSION: Both laparoscopic and endoscopic approaches are feasible for removing stones in the common bile duct in patients with gastrojejunostomy after gastrectomy, and they complement each other. In addition, both techniques are difficult to conduct, and a technical competence should be considered in selection of each method.

[Laparoscopic treatment for pancreatic pseudocysts].

Pancreatic pseudocyst is the most common pancreatic cystic disease in clinical practice.In the surgical treatment of pancreatic pseudocysts, most surgeons preferred laparoscopic surgery in recent years.The options and the timing of laparoscopic surgery for pancreatic pseudocysts in different situations are explored in the paper.Pancreatic pseudocysts during the observation period, the imaging examination to detect whether the cyst has disappeared or increased, such as cysts found to be enlarged or still can not dissipate after 6 months, the largest diameter greater than 6 cm, and clinical symptoms, surgical drainage should be considered treatment.Surgery based on the location of the cyst and surgical experience of surgical options.Pancreatic cyst often choose laparoscopic cyst-gastric anastomosis, far from the stomach cyst should choose laparoscopic cyst-jejunal anastomosis.Laparoscopic surgery for the treatment of pancreatic pseudocyst has a unique advantage, short operation time, less bleeding, less trauma, less postoperative complications, rapid recovery, is a safe and effective treatment options.

[Surgical strategies for treatment of T1b gallbladder cancers diagnosed intraoperatively or postoperatively].

OBJECTIVE: To explore the surgical strategies for the treatment of T1b gallbladder cancer patients diagnosed intraoperatively or postoperatively. METHODS: A retrospective analysis of 42 patients with T1b gallbladder cancers was performed. There were 14 patients diagnosed intraoperatively and 28 patients diagnosed postoperatively. The reevaluations of T stages were conducted in the 28 T1b gallbladder cancer patients diagnosed postoperatively by the professional pathologist. After T stage reevaluation, 25 confirmed T1b patients with complete follow-up data were divided into simple cholecystectomy group and ra-dical resection group, and the clinicopathologic characteristics between the two groups were analyzed. RESULTS: Only 2 of the 14 T1b gallbladder cancer patients diagnosed by the intraoperative frozen specimen proved to be T1b on postoperative paraffin pathology, and for the remaining 13 patients, T2 was in 11 patients, and T3 in one patient. The rate of misdiagnosis was 85.7% by the intraoperative frozen specimens, postoperative T stages were equal or higher than intraoperative T stages. Two of the 28 postoperatively diagnosed T1b patients were proved to be T2 after reevaluation, the rate of misdiagnosis was 7.1%, the reevaluated T stages were equal to or higher than the previous stages. Twenty-five confirmed T1b gallbladder cancer patients had complete follow-up data, 11 of whom underwent simple cholecystectomy and the remaining 14 radical resections. No patient had vessel or perineural invasion on pathology in the 25 confirmed T1b patients. Metastasis was absent in all the 30 lymph nodes examined, which achieved from 14 patients with radical resection. The survival rate after simple cholecystectomy was comparable to that after radical resection (P=0.361). Only one patient with radical resection had abdominal cavity implantation relapse, who received gallbladder compression during operation and 2 years later died from metastasis. CONCLUSION: Intraoperatively diagnosed T1b gallbladder cancer should receive radical resection. Reevaluation of the T stage is necessary and the initial step for postoperative diagnosed T1b gallbladder cancer patients. The pros and cons of radical surgery for definitive T1b patients should be carefully evaluated, and systemic chemotherapy is recommended for those with bile spillover.

[The treatment options of pancreatic neuroendocrine neoplasm with liver metastasis].

Liver metastasis is the one of the main prognostic factors of pancreatic neuroendocrine neoplasm (PNEN). With the development of multidisciplinary collaboration among surgical oncology, medical oncology, and intervention treatment, the treatment of PNEN with liver metastasis gradually tends to become diversification. Surgery is still the only way for curing the patients with pancreatic neuroendocrine tumor with liver metastasis when the histological types are G1 and G2. Medical oncology and intervention treatment could be selected for those having PNEN with diffuse liver metastasis or those cannot tolerate surgery. Liver transplantation only suits for a small number of selected patients. The present article explored the relationship between histological classifications and the treatment options of PNEN with liver metastasis, and discussed the specific treatments from perspectives of surgical treatment, medical treatment and intervention treatment.

Adaptive transfer of B10 cells: a novel therapy for chronic rejection after solid organ transplantation.

Chronic rejection occurs between almost all MHC-mismatched donors and recipients after transplantation. Immunosuppressive agents have been administrated indiscriminately to manage potential rejection, but complications from lifelong immunosuppressive therapy threaten transplant recipients. Recent studies demonstrated that a number of regulatory B cells (B10 cells) negatively regulate T cell mediated immune responses without inducing systemic immune suppression. Therefore, we propose that adaptive transfer of B10 cells suppresses alloreactive CD8(+) cytotoxic T cell activation induced by allogeneic solid organ transplantation, reduces T cell mediated rejection and prolongs allograft survival.

Metabonomic analysis of rats with acute heart rejection.

BACKGROUND: Organs transplantation is an effective treatment for end-stage organ failure. Despite the use of modern immunosuppressants to decrease its incidence, acute rejection episodes (ARE), still present a problem for diagnosis, resolution, and prediction of long-term outcomes due to the absence of sufficiently robust biomarkers. METHODS: Using an heterotopic heart transplantation model using Dark Agouti to Lewis rats, and sirolimus (rapamycin, Rapa) treatment by gavage, we divided recipients into four groups: controls, ARE, Rapa-14, and Rapa-7. We evaluated recipients by hematoxylin and eosin staining of grafts and reverse transcription polymerase chain reactions. Levels of plasma metabolites were quantified using gas chromatography/time-of-flight mass spectrometry. Data were evaluated employing partial least-squares discriminant analysis (PLS-DA), the area under the receiver operating characteristic curves with negative predictive values (NPV) and positive predictive values (PPV). RESULTS: The graft survival was prolonged by Rapa. Plasma levels of 10 metabolites differed significantly between the ARE and the Rapa-14 groups as illustrated by the total ion current. According to PLS-DA, proline, glycine, serine, phenylalanine, and isocitrate showed the greatest effects with areas under the curve of 0.944, 0.917, 1.0, 0.861, and 0.944 respectively. The NPV values were 85.7%, 85.7%, 100%, 83.3%, and 85.7% and PPV values, 100%, 100%, 100%, 83.3%, and 100% respectively. Therefore, these metabolites may be used to predict the occurrence and progression of ARE. CONCLUSION: The trend of changes suggested that plasma metabolites correlated with the immune state of recipients. Therefore, metabonomics may provide new biomarkers for graft injury in the early phases of ARE.

Chronopharmacology of oral prednisolone in rats.

The chronopharmacology of oral prednisolone (PSL) was studied in rat models. Differences in the dosing-time-dependent toxicity were evaluated at four time points (3, 9, 15 and 21 HALO) in adult male Wistar rats and confirmed in an inbred strain of Lewis rats (MHC haplotype; RTIl) at two time points (9 and 21 HALO). The total body weight and that of the immunologic-related organs were maximally reduced when PSL was repeatedly administered during the late active phase (21 HALO). This chronotoxicity was independent of plasma concentrations of PSL, adrenocorticotropic hormone, and corticosterone. Repeated administration of PSL prolonged cardiac allograft survival in a DA (RTIa) -to-Lewis combination, and there was a tendency to be more effective in the 21 HALO trial. These results suggested that single dose therapy of PSL at the selected point of the day may be less harmful, protecting against allograft rejection.

Dosing time-dependent pharmacological effects of anti-metabolites for rat cardiac graft.

Antimetabolites such as methotrexete and 6-mercaptopurine have been shown to have circadian variations in their toxicities. However, chronopharmacological profiles of mizoribine (Miz) that is newly synthesized as an anti-metabolic agent for immunosuppression, have not been evaluated. In this study, we examined the dosing time-dependent alterations in the pharmacokinetics and pharmacodynamics of Miz. In addition, chronopharmacology of azathiopurine (Aza) was also evaluated to compare with that of Miz. Initially, Miz (10 and 20 mg/kg) or Aza (20 mg/kg) was orally administered at 8:00 hr or 20:00 hr for 3 weeks to rats. To reveal the dosing time-dependent difference of pharmacokinetics, Miz (20 mg/kg) was orally given at 8:00 hr or 20:00 hr and blood was obtained for 12 hours. Finally, Miz (20 mg/kg) or Aza (20 mg/kg) was administered at 8:00 hr or 20:00 hr to rats with heterotopic allogeneic heart grafts. The Miz group treated at 8:00 hr and Aza group treated at 20:00 hr showed severe myelosuppression compared with their each opposite dosing time. AUC of Miz in the morning trial was twice as high as that in the evening trial. The graft survival durations of the Miz- and Aza-treated groups were significantly longer than those of the respective control groups, but were not affected by dosing time of each agent. These results suggest that the toxicity, but not efficacy of Miz is varied with the dosing time. The chronotoxicological phenomenon of Miz might be, at least in part, explained by the dosing time-dependent difference in serum drug concentrations and apparent clearance.