ПОВРЕЖДЕНИЕ ПРОТОКА ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ ПРИ ОСТРОМ НЕКРОТИЧЕСКОМ ПАНКРЕАТИТЕ И ЕГО ПОСЛЕДСТВИЯ
Objective. To study signs of pancreatic duct disruption in the early phase of necrotizing pancreatitis.
Material and methods. Contrast-enhanced CT was performed in 227 patients, in 67 patients – on the 2nd and 3rd days from the disease onset. Damage of the pancreas was estimated according to the configuration of necrosis: the depth of necrosis in the sagittal plane (transverse necrosis) and the mutual location of necrosis and healthy parenchyma. At the 1st type of configuration it was more distal than necrosis, at the 2nd type – absent. Peripancreatitis was assessed according to Ishikawa criteria, we studied alpha-amylase activity in fluid collections. The effect of the depth of necrosis and its volume (the Balthazar criterion) on the severity of peripancreatitis was compared.
Results. Necrotizing pancreatitis was detected in 200 patients: in 132 patients – type 1 (necrosis of the head, isthmus, body, initial part of the tail), in 30 – type 2 (necrosis of the tail), in 38 – necrotizing pancreatitis with localization of acute necrotic collections only in the retroperitoneal tissue. Advanced peripancreatitis was revealed in 80% of patients at early term and was present in 19 of 26 patients with early organ failure. It was more severe in type 1 in comparison with type 2 by Ishikawa criteria (5.28 ± 0.25 vs 4.27 ± 0.43, p < 0.05), by accumulation volume (278 and 166 cc, p < 0.05), by presence of high (over 1000 units/L) alpha-amylase activity 1in fluid. The depth of necrosis greater than the volume determined the degree of peripancreatitis in the first and second CT studies (data from multivariate variance and regression analyses).
Conclusion. Deep transverse necrosis in patients with type 1 configuration and high alpha-amylase activity in fluid collections are early signs of disconnected pancreatic duct syndrome. They determine the severity of peripancreatitis and systemic complications. Computed tomography allows you to diagnose this in the first 2–3 days from the onset of the disease.
Aim. To determine the indications for early interventions in patients with acute pancreatitis and disconnected pancreatic duct syndrome, and evaluate their effectiveness.
Material and methods. The study included 180 patients: type 1 of the necrosis configuration was detected in 150, type 2 – in 30. The diagnosis of disconnected pancreatic duct syndrome was established according to CT data (type 1 of pancreatic necrosis) and high activity of alfa-amylase in fluid collections. The patients underwent various treatments: only conservative (50), percutaneous punctures / drainage of collections (33), surgery (54), 2-stage treatment (percutaneous punctures / drainage at 1–2 weeks and sequestrectomy at 3-5 weeks) – in 25. In 18 patients with type 1 necrosis, endoscopic recanalization of the pancreatic duct through the zone of transverse necrosis was performed on days 1–4 from the onset of the disease.
Results. The overall mortality rate was 22.8%: with type 1 of the necrosis configuration – 26.6%, with type 2 – 3.3%, p < 0.01. Conservative treatment and percutaneous punctures were effective in 22 (73%) patients with type 2 necrosis configuration and in 53 (35%) with type 1 with shallow necrosis and the absence of high alpha-amylase activity in the fluid. In patients with disconnected pancreatic duct syndrome, the mortality rate in 2-stage treatment was 9%, which was significantly lower than in early (58%) and late (39%) surgery.
Conclusion. The indication for early intervention is the high activity of alpha-amylase in fluid collections with type 1 necrosis configuration. Early interventions should be minimally invasive and aimed at transferring an internal fistula to an external one. This prevents the progression of parapancreatitis and allows to perform stage 2 (sequestrectomy) at a later date. Two-stage treatment significantly reduces mortality compared to early and late surgery.
Aim. Improvement of treatment results in patients with necrotizing pancreatitis and signs of the dissociation between the distal and proximal parts of the pancreas by using endoscopic transpapillary stent placement.
Material and methods. There were 25 patients with acute necrotizing pancreatitis and disconnected pancreatic duct syndrome, which have been managed by using endoscopic transpapillary stent placement throughout 2018-2020. Twenty patients have been admitted into hospital in first 24-72 hours of onset, while 5 patients – later than 72 hours. We have diagnosed necrotizing process located in the head and the neck of the pancreas and peripancreatic space in all these patients (“Model III”).
Results. Positive results related to transpapillary stent placement were noted in 18 patients (72% – main group). Sixteen patients from this group were admitted into hospital in first 24–72 hours, two patients – later than 72 hours from the disease onset. Transpapillary stent placement failed in 7 (28%) patients (control group). Complications in the main group occurred in 2 patients (11,1%): in one case – the dislocation of stent into duodenum and one patient with bleeding after papillosphincterotomy, infected necrotized pancreatitis developed in 4 patients. Mortality observed in 1 case (5.5%).
Complications among control group occurred in 2 patients (28.6) – arrosive bleeding, infected necrotized pancreatitis developed in 3 patients. Mortality observed in 1 case (14.3%).
Conclusions. Endoscopic transpapillary stent placement is an effective minimally invasive approach in management of patients with necrotizing pancreatitis.
Aim. To analyze the outcomes of pancreatic necrosis depending on the depth and localization of damage to the pancreatic tissue, to determine the main risk factors for the development of external and internal pancreatic fistulas.
Materials and methods. The analysis of long-term results of treatment of pancreatic necrosis in 81 patients was carried out: 53 patients were treated at the stage of acute pancreatitis in our clinic, 28 – in other medical institutions. The algorithm of the survey included a CT scan with contrast enhancement, fistulography, MRI-pancreatocholangiography and/or endoscopic retrograde cholangiopancreatography. The influence of various factors on the development of pseudocysts and pancreatic fistulas was estimated using the Spearman correlation coefficient.
Results. Signs of damage to the pancreatic duct were detected in 19 (36%) of 53 patients: 9 were diagnosed with pseudocysts, 10 had external pancreatic fistulas. The daily flow rate of pancreatic juice (α-amylase activity >20950 u/l) was 300–350 ml. Interventions (minimally invasive, open surgery) required 10 patients (52.6%). The correlation coefficient of external pancreatic fistulas with the depth of pancreatic necrosis was 0.46 (р = 0.00005), the CT severity index according to Balthazar – 0.05 (р = 0.63), the localization of necrosis in the neck – 0.31 (р = 0.006), the amount of drainage discharge – 0.55 (р = 0.000001), the activity of α-amylase fluid – 0.53 (р = 0.000002). There was a significant positive correlation of mediastinal pancreatogenic cysts with pseudocysts located on the posterior surface of the pancreas (r = 0.7; p = 0.003), pleural effusion with high activity of α-amylase (r = 0.87, р = 0.0005) and alcoholic etiology of acute pancreatitis (r = 0.75, р = 0.002).
Conclusion. Predictors of resistant to conservative treatment external pancreatic fistulas are deep necrosis, especially in the area of the neck of the pancreas, the discharge flow rate through the drainage is more than 150 ml with an α-amylase activity of more than 1000 u/l. A risk factor for the development of internal pancreatic fistulas with penetration into the mediastinum is the localization of pseudocysts on the posterior surface of the pancreas in the body and tail area.
Aim: improving the results treatment of patients with severe acute pancreatitis by early diagnosis fulminant course of the disease and development of individualized treatment tactics based on early surgical interventions with perioperative extracorporeal detoxification
Materials and methods: In research analyzed the treatment of 232 patients with severe acute pancreatitis: 175 patients were evaluated retrospectively (control group), 57 were included in a prospective study (main group). The severity of the disease was studied using integral scales, necrosis of the pancreas (its localization, depth) and the prevalence of parapancreatitis (gradations according to Ishikawa et al.) - according to CT data. The tactics of treatment at the retrospective stage of the study was based on the current Clinical Recommendations, at the prospective stage - on the developed signs of a "fulminant" course of the disease and included early operations with perioperative extracorporeal detoxification.
Results: Criteria for a fulminant course of severe acute pancreatitis were found in 41 (23%) of 175 and 24 (42%) of 57 patients. According to the scale values (APACHE II ≥ 16 Ranson ≥ 8, SOFA ≥ 7 points) in the first 48 hours from the onset of the disease, the presence of aseptic enzymatic peritonitis, the depth of necrosis in the region of the head and body of the pancreas ≥50%, intra-abdominal hypertension of the III-IV degree, significant differences with similar indicators in 134 and 33 patients with severe acute pancreatitis. With fulminant course in the control and main groups, all 5 patients who received only conservative treatment died, 33 (86.8%) and 9 (40.9%) after operations, χ2 = 13.32, p<0.001. Mortality in severe acute pancreatitis, excluding patients with fulminant course, was comparable in the groups, being 15.7% and 15.2%, χ2 = 0.450, p> 0.05.
Conclusion: Patients with severe acute pancreatitis represent a heterogeneous group. The morphological substrate of "fulminant" pancreatitis is deep (more than 50%) necrosis with localization in the head and body of the pancreas and widespread parapancreatitis. The developed individualized approach to treatment allows predicting an unfavorable course in the first 48 hours after the onset of the disease. Early operations in the nature of detoxification, decompression and drainage interventions, with perioperative use of extracorporeal detoxification methods allowed to reduce mortality from 86.8% to 40.9%.
A clinical observation of a successful staged treatment of a patient with severe acute pancreatitis based on early diagnosis of damage to the pancreatic duct according to CT data (configuration of pancreatic necrosis) and high level of amylase in the fluid collection is presented.
LIVER
Aim. To study the long-term results of liver transplantation for hepatocellular carcinoma in accordance with various criteria for selecting patients for surgery.
Materials and methods. The results of 71 liver transplantations for hepatocellular carcinoma have been studied. Long- term survival and disease-free survival have been studied in accordance with various criteria for selecting patients for liver transplantation.
Results. The five-year survival rate was 84.3%, the median survival rate was 47.4 months. Higher overall survival and disease-free survival rates were found in patients after living donor liver transplantation compared to patients after cadaveric liver transplantation. The five-year survival rate for patients within the Milan criteria compared to those beyond the Milan criteria were 92.4% vs 74.1%. The five-year survival rate for patients within the UCSF criteria compared to patients beyond the UCSF criteria were 93.3% vs 68.3%. The five-year survival rate for patients within the Up-to-seven criteria compared to patients beyond the Up-to-seven criteria were 88.4% vs 71.0%. The five-year survival rate for patients within the Hangzhou criteria compared to patients beyond the Hangzhou criteria were 84.4% vs 72.9%. Hepatocellular carcinomas recurrent were in 8.4% of patients in the long-term period of liver transplantation. The five-year disease-free survival rate among all patients was 87.7%. The median disease-free survival rate was 43.2 months. The five-year disease-free survival rate for patients within criteria were from 85.4% (Hangzhou University) to 93.3% (UCSF). The five-year disease-free survival rate for patients beyond criteria were from 68.3% (UCSF) to 74.1% (Milan criteria). A statistically significant relapse rate was observed in patients with a Guerrini coefficient >2.3, regardless of the selection criteria in all study groups of patients.
Conclusion. The optimal prognostic criteria for liver transplantation for patients with hepatocellular carcinoma are the Milan criteria. Some expansion of the Milan criteria show comparable results. In this regard, it can be assumed that the optimal criteria have not been found at present, which requires new ways to search for expansion of the Milan criteria, taking into account the level of AFP, tumor differentiation, etc.
Aim. To improve the results of the treatment of colorectal cancer with hepatic metastases in patients over 60 years old by applying selective chemoembolization of the hepatic artery.
Materials and methods. At the Central Clinical Hospital “Railways-Medicine“, 20 patients over 60 years old with colorectal cancer liver metastases were treated. Ten patients in the control group received systemic chemotherapy. In the main group, 10 patients underwent chemoembolization of the hepatic artery using microspheres saturated with doxorubicin. Treatment results were assessed using the RECIST 1.1 scale. We considered the immediate and long- term results up to 12 months after the treatment.
Results. A partial response according to the RECIST 1.1 scale was detected in 4 patients from the main group (40%), stabilization of the oncological process in the liver in 2 (20%) patients, progression of the metastatic process was detected in 4 (40%) patients. There were no deaths within 12 months after the chemotherapy. In the control group, stabilization was observed in 2 (20%) patients after systemic chemotherapy according to the RECIST 1.1 scale, and progression was diagnosed in 8 (80%) patients. One death (10%) was noted during the observation period.
Conclusion. The use of selective chemoembolization of the hepatic artery in the main group of patients has shown its effectiveness while preserving a satisfactory quality of life (QLP).
PANCREAS
Aim. Analysis of the results of the application of the modified step-up approach in the treatment of infected pancreatonecrosis in a third-level hospital.
Materials and methods. The study included 52 patients over 18 years of age with acute pancreatitis and suspected or proven infection with pancreatic or peripancreatic necrosis .The control group included 27 patients who underwent primary open necrectomy. The comparison group included 25 patients who underwent surgical treatment within the framework of the modified concept of the stepwise surgical approach (Step-up). In the groups compared mortality rates, early postoperative complications (IIIb-IVb grade Clavien-Dindo), late postoperative complications (ventral hernias, pseudocysts, diabetes mellitus), the duration of inpatient treatment, and the duration of treatment in the intensive care unit. The indicator "Full return to primary social activity after treatment" was also proposed.
Results. In the Step-up approach group, in comparison with the control group, there was a decrease in the overall incidence of postoperative complications of IIIb-IVb grade Clavien-Dindo (24% and 51.9%, respectively, p <0.05), the frequency of arrosive bleeding (0% and 14 , 8%, respectively, p <0.05), the need for necrsequestrectomy (64 and 100%, respectively, p <0.01), the total average duration of treatment in the intensive care unit (3.2 ± 0.6 and 9.2 ± 1.6 days, respectively, p <0.05), and the average duration of treatment in the intensive care unit after execution of necrosectomy (1,4±0,4 7,2±1,3 days, respectively, p<0.01). A complete return to social activity in the control group was noted only in 10 (37%) patients compared with 19 (76%) in the Step-up group (p <0.01). In the Step-up group, in comparison with the control group, a tendency towards a decrease in mortality was revealed (16% and 34.5%, respectively, p> 0.05).
Conclusion. The step-up approach can improve the results of treatment of infected pancreatic necrosis. The most important advantage of this concept is reproducibility - that is, the possibility of using it not only in the leading metropolitan clinics, but also in the regions of the Russian Federation. The step-up approach, however, has not yet acquired a complete form, and there is room for improvement.
Aim. To determine the role of microcirculation disorders in association with the C774T polymorphism of the eNOS gene in the progression of acute pancreatitis.
Materials and methods. We investigated 90 patients with acute pancreatitis. In 30 patients of group 1, a mild course of acute pancreatitis was noted, in 30 patients in group 2 – moderate severity of the disease, in 30 patients in group 3 – severe acute pancreatitis. The state of microcirculation was evaluated by LACK-02 apparatus (NPO “Lazma”, Russia). The molecular genetic testing of eNOS gene polymorphism (C774T) was performed using DNA samples (isolated from peripheral blood) by real-time polymerase chain reaction (CFX96 Touch™ Real-time PCR Detection System, USA). The study design is prospective. The evidence level – II.
Results. It has been established that in the early stages of acute pancreatitis occur microcirculatory disorders (a depression of the microcirculation index, coefficient of variation, and microcirculation efficiency index), which associated with the severity of the disease. In mild and moderate forms, these changes were stopped by using standard therapy to sixth day of illness. In patients with acute severe pancreatitis these changes persisted. It should be noted that microcirculation disorders were more significant in patients with the T774T polymorphism of the eNOS gene. The most frequent (56.3 %, C' = 0.880, p = 0.001) such pathological phenomena were registered in severe form of the disease, which is an important argument for adjusting personalized therapy.
Conclusion. The presence of T774T polymorphism of the eNOS gene in patients with acute pancreatitis, associated with an increased level of nitric oxide production, leads to the development of microcirculatory disorders, which should be recognized as one of the risk factors for disease progression and development of complications.
BILE DUCTS
Aim: comparative study of the immediate and long-term results of combined treatment of patients with pancreatobiliary cancer of the ampulla of Vater.
Materials and methods. From 2001 to 2019 21 patients with pancreatobiliary cancer of the ampulla of Vater underwent curative treatment. It included preoperative radiotherapy, extended Wipple procedure and adjuvant chemotherapy as indicated (main group). In 48 cases of pancreatobiliary cancer of the ampulla of Vater extended Wipple procedure and adjuvant chemotherapy according to indications was performed (comparison group). In 43 cases of intestinal cancer of the ampulla of Vater extended Wipple procedure and adjuvant chemotherapy according to indications was performed.
Results. Postoperative complication and mortality in the study group and the comparison group were 14.3% and 35.4% (p = 0.07), 4.8% and 6.3% (p = 0.8). Overall 5-year survival rate, median survival were 50.7% and 9.8% (p = 0.01), 51 (36.5–115) mo. and 10 (4–29) mo. (p = 0.0008). Overall 5-year survival rate, median survival in the group of intestinal cancer of the ampulla of Vater accounted for 61.3 % and 44 (17–85.5) mo. One-year disease-free survival in patients with adenocarcinoma of the ampulla of Vater who have undergone curative treatment was 77.8%, 3-year survival – 51.0%, 5-year survival – 35.2%, median is 22 (9–54) mo.
Conclusion. Preoperative radiotherapy in curative treatment of pancreatobiliary cancer of the ampulla of Vater did not result to a change in the nature and an increase in the postoperative complications rate.
Combination treatment for pancreatobiliary cancer of the ampulla of Vater significantly improved long-term survival.
REVIEWS
The literature review is devoted to the analysis of the main methods of treatment of patients with colorectal cancer liver metastases. The analysis of the clinical trials results over the past 10 years has been carried out. Colorectal cancer is the common malignant neoplasm. About 20% of patients have distant metastases in the diagnosing. Liver is the most frequent targeted organ, liver metastases are detected in 14,5% of patients with colorectal cancer. Despite the encouraging results of treatment of certain groups of patients with metastatic colorectal cancer, the treatment tactics for most patients is limited to palliative chemotherapy. In recent years, the survival of patients with metastatic colorectal cancer has significantly improved due to the success of systemic therapy. The median overall survival has reached for 2 years due to combination chemotherapy based on fluoropyrimidines, oxaliplatin, irinotecan in combination with monoclonal antibodies (bevacizumab, cetuximab and panitumumab). The optimal combination and sequence of using these anticancer agents in the treatment of metastatic colorectal cancer has not yet been determined. Surgery is the standard of care for this category of patients. At the same time, until nowdays there are no clear and generally accepted criteria for choosing the optimal volume of surgical intervention, prescribing first-line chemotherapy and using other methods of antitumor treatment.
A literature review is devoted to the current classifications of liver failure that occurs in obstructive jaundice. Modern methods of diagnosis and criteria for determining the time of development and assessing the severity of this disease, model assessment and prognosis of acute liver failure are also considered. Attention is paid to assessing the severity and determining the timing of the development of liver failure in extrahepatic cholestasis. In addition, there is no common understanding of the role of liver compensatory mechanisms involved in the development of this condition. There are no generally accepted views on the surgical tactics of treatment of patients with obstructive jaundice complicated by liver failure. The limits of application of step-by-step treatment of patients with neoplastic obstructive jaundice have not been reliably determined. All these issues require further research, search for universal tools for assessing liver failure, predicting postoperative complications for choosing the optimal surgical treatment tactics.
EXPERIMENTAL STUDY
Aim: comparative assessment of the effectiveness of hemostatic materials in an acute experiment in vivo.
Materials and methods. We studied samples of hemostatic materials TachoComb (No. 1), Gelita-Spon Standard (No. 2), Surgicel Fibrillar (No. 3), samples of hemostatic sponges developed jointly with LLC ”Lintex“ (St. Petersburg, Russia) based on sodium carboxymethyl cellulose ( Na-CMC): Na-CMC + Tranexamic acid, pressed (No. 4), Na-CMC + Tranexamic acid, uncompressed (No. 5), Na-CMC pressed (No. 6), Na-CMC uncompressed (No. 7). Rats under general anaesthesia were given a middle laparotomy, and the partial liver resection of the left liver lobe was simulated. The bleeding was stopped by application of test materials. Blood loss volume (blood volume absorbed by one sample), bleeding time were evaluated. We applied nonparametric criterion of Mann-Whitney (p ≤ 0.05) to determination of reliability of differences.
Results. The lowest values of the index ”Bleeding time“ are observed in experimental groups No. 4-No. 7. Among the samples of these groups there are the following statistically significant differences: the values of the samples of group No. 4 are 1.5 times higher than that of sample No. 5; 2.68 times – group No. 6; 2.41 times – groups No. 7. The values of samples of group No. 7 are 1.74 times less than samples of group No. 5 and 4 seconds more than in group No. 6. When comparing blood loss volume in investigated groups, fewer statistically significant differences are observed. But the values of the samples of group No. 2 significantly exceed the values of all experimental groups.
Conclusion. The use of a local hemostatic agent based on Na-CMC (with and without the addition of tranexamic acid) in stopping bleeding after the partial liver resection in laboratory animals (rats) is no less than clinically introduced applicational hemostatic agents such as TachoComb, Gelita-Spon Standard and Surgicel Fibrillar.
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