Vol 52, No 5 (2024)

Cover Page

Full Issue

ARTICLES

Is there a place for surgery in oligometastatic ductal carcinoma of the pancreatic head?

Egorov V.I., Kotelnikov A.G., Patyutko Y.I., Podluzhny D.V., Polyakov A.N., Kudashkin N.E., Daminov A.N.

Abstract

Background: New chemotherapy regimens (gemcitabine / nab-paclitaxel, FOLFIRINOX) have improved overall survival rates in ductal carcinoma, which has renewed the interest in surgical treatment for isolated liver metastases.

Aim: To identify the role of surgery in ductal carcinoma of the pancreatic head with liver oligometastases.

Methods: We retrospectively analyzed the data from 490 patients with morphologically verified ductal carcinoma of the pancreatic head in two specialized centers, who had undergone pancreatoduodenectomy (PD) from January 2011 to April 2024. In 21 patients, PD was performed simultaneously with liver resection (liver oligometastases were found during the surgery).

Results: In the postoperative period after PD with liver resection, compared to that after PD without liver resection, intra-abdominal abscesses were more frequent (4/21 (19.0%) versus 10/469 (2.2%), p = 0.002) and relaparotomy was performed more often by 9.8% [95 confidence interval (CI, Miettinen-Nurminen score method) 0.21–30.3] (3/21 (14.3%) versus 21/469 (4.5%), p = 0.077). The postoperative death rates were comparable (1/21 (4.8%) versus 19/469 (4.1%), p = 0.8). The median overall survival of the patients after PD with liver resection was 11 (95% CI: 6–16) months, and overall 1-, 2-, and 3-year survival rates were 39.2, 16.8 and 7.2%, respectively. In the patients after PD with liver resection without any adjuvant chemotherapy (n = 5), the median overall survival was 6 (95% CI: 5–7) months, and in those with chemotherapy, 13 (95% CI: 6–16) months (p = 0.006). The overall three-year survival of the patients after PD with liver resection and adjuvant chemotherapy was 11.5%. In the patients after PD with liver resection R0, the median overall survival was 13 (95% CI: 6–32) months, with R1 resection 6 (95% CI: 6–7), and with R2 resection 6 (95% CI: 6–7) months (p = 0.021). The median overall survival of patients after PD with liver resection for G1 tumors was 17 (95% CI: 6–32) months.

Conclusion: Surgery as a component of combination therapy for oligometastatic pancreatic head cancer can be considered in a certain category of patients with high tumor differentiation grade and mandatory preliminary assessment of the feasibility of R0 surgery and systemic chemotherapy.

Almanac of Clinical Medicine. 2024;52(5):249-258
pages 249-258 views

Low sensitivity of chromogranin A in the diagnosis of insulinoma: a single-center study

Yukina M.Y., Troshina E.A., Nuralieva N.F., Rebrova O.Y., Nikankina L.V., Mokrysheva N.G.

Abstract

Background: Insulinoma is a neuroendocrine tumor (NET), with its main clinical manifestation being the hypoglycemic syndrome. The symptoms of hypoglycemia are nonspecific, and therefore, in most cases, the diagnosis is made untimely. The Russian clinical guidelines for the diagnosis and treatment of NET suggest as a diagnostic test that the universal circulating marker of all NET, chromogranin A (CgA) be determined. However, the literature data on the sensitivity of CgA in the diagnosis of insulinoma are contradictory.

Aim: To evaluate the diagnostic effectiveness of the CgA test in the diagnosis of insulinoma.

Materials and methods: This was a hospital-based single-center, cross-sectional comparative (first step) and prospective non-comparative (second step) study conducted from 2016 to 2022. During the first part of the study, we determined serum CgA in 120 patients with suspected non-diabetic hypoglycemia and compared its levels in the patients with and without confirmed insulinoma (n = 87 and n = 33, respectively). During the second study step, CgA was measured in the insulinoma patients at 6 [4.0; 7.0] months after surgery. The CgA levels at baseline and post-surgery were analyzed in 74 patients (those with recurring non-diabetic hypoglycemia were excluded from the analysis).

Results: In the study subjects without insulinoma, the median CgA level was 0.7 [0.5; 1.1] (range, 0.1 to 2.0) nmol/l and the difference (with Bonferroni adjustment) from its levels in the patients with insulinoma before surgery was non-significant (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, р = 0.045). The CgA concentration in the insulinoma patients after surgery was 0.9 [0.7; 1.2], range, 0 to 1.9 nmol/l and significantly differed from that at baseline (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, p = 0.012, Wilcoxon test). In the patients with insulinoma before surgery the CgA levels exceeding the generally accepted reference range (> 2 nmol/l) was found in 11.5% (n = 10), with its median level of 2.5 [2.3; 4.1], range 2.3 to 8.5 nmol/l. There were no significant associations between the CgA levels and localization, tumor numbers, their size and malignization grade, insulin and proinsulin values, and duration of fasting. The sensitivity and specificity of the CgA test were 12% [95% confidence interval [CI]: 6%–20%] and 100% [95% CI: 97%–100%], respectively. The prognostic value of a positive result (PVPR) was 100% [95% CI: 69%–100%] and the prognostic value of a negative result (PVNR) 30% [95% CI: 28%–32%].

Conclusion: As a diagnostic test, CgA has high specificity and prognostic value of a positive result. However, the uncertainty of the prognostic value of a negative result is unacceptably high. A special study is required to clarify the operational characteristics of CgA in insulinoma.

Almanac of Clinical Medicine. 2024;52(5):259-268
pages 259-268 views

An association between the blood perfusion parameters in foot tissues and the severity of arterial occlusion and stenosis in the lower extremities

Krasulina K.A., Glazkova P.A., Glazkov A.A., Selivanova D.S., Zagarov S.S., Vataev A.V., Larkov R.N., Rogatkin D.A.

Abstract

Rationale: Peripheral artery disease (PAD) is common among the elderly and increases the risk of cardiovascular events, disability and death. PAD course and outcomes depend not only on the condition of macrovasculature but also on the tissue perfusion. We have previously shown that Type 2 diabetic patients with lower extremity ischemia have significantly lower perfusion than healthy volunteers, and the ratio of basal perfusion in the arm and leg (BP1/BP3) measured by incoherent optical fluctuation flowmetry (IOFF) allows to identify hemodynamically significant stenoses.

Aim: To analyze associations between perfusion parameters registered by IOFF and the severity of vascular involvement in PAD patients.

Methods: This single center cross-sectional study included 38 PAD patients admitted to the Department of Vascular Surgery and Coronary Artery Disease. The arteries were assessed with duplex Doppler ultrasonography (DDU), according to the results of which the PAD severity score and ankle-brachial index (ABI) were calculated. Skin microhemodynamic parameters were recorded by IOFF. The basal perfusion on the arm (BP1), the dorsal foot surface and the toe (BP2 and BP3), the ratio BP1/BP3, local thermal hyperemia (LTH2 and LTH3) and an increase in perfusion after heating on two leg zones (LTH2-BP2, LTH3-BP3) were evaluated and expressed in perfusion units (PU). BP1, BP3, and BP1/BP3 values were additionally measured with laser Doppler flowmetry (LDF). The analysis was performed depending on the degree of arterial involvement determined by DDU for each limb separately (n = 73). There were ≥ 50% stenoses in 15 extremities (Group 1), occlusion of one of the major arteries in 42 (Group 2) and ≥ 2 occlusions in 16 lower extremities (Group 3).

Results: In the groups 1, 2 and 3, the values of most parameters estimated by IOFF decreased with an increase in severity of limb lesions. As an example, the respective perfusion parameters for the big toe in the study groups were as follows: BP3 4.0 [2.0; 9.8], 2.2 [0.9; 3.7] and 1.1 [0.7; 2.6] PU (p = 0.007); LTH3 10.0 [6.4; 14.9], 5.0 [1.5; 7.8] and 2.5 [1.4; 4.5] PU (p < 0.001), and LTH3-BP3 3.8 [2.6; 7.8], 2.4 [0.6; 4.3] and 1.2 [0.4; 1.5] PU (p = 0.001). The BP1/BP3 ratio in the above mentioned group increased: 1.8 [0.8; 7.7], 7.2 [3.4; 21.3] and 14.2 [6.6; 18.3] (p = 0.004), respectively. No similar trend was found for this parameter registered by LDF. There were significant correlations between the lower extremities perfusion parameters measured by IOFF and ABI, with the correlation coefficients ranging from 0.365 to 0.717 (p < 0.05).

Conclusion: The functional parameters of the skin microhemodynamics vary with different PAD severity. In addition, they correlate with clinical indicators of atherosclerosis. The IOFF technique can be promising as an additional quantitative method for assessment of microvascular blood flow in patients with PAD.

Almanac of Clinical Medicine. 2024;52(5):269-279
pages 269-279 views

REVIEW ARTICLE

Chronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbiotics

Serkova M.Y., Avalueva E.B., Sitkin S.I.

Abstract

Chronic constipation is a global medical, social, and economic problem due to its negative impact on patients’ quality of life and increased risk of colorectal cancer, cardiovascular and cerebrovascular disorders.

The gut microbiota plays an important role in the pathophysiology of constipation through its interplay with the immune system, enteral and central nervous system, representing a promising therapeutic target. Gut dysbiosis in patients with constipation is characterized by reduced relative numbers of bacteria producing lactate (Lactobacillaceae, Bifidobacteriaceae) and butyrate (Lachnospiraceae, Oscillospiraceae), as well as with increased numbers of those producing hydrogen sulfide (Desulfovibrionaceae) and methanogenic archaea (Methanobacteriaceae). The leading pathogenetic mechanism related to intestinal dysbiosis in chronic constipation, can be microbial metabolic abnormalities (metabolic dysbiosis) characterized by altered production of short-chain fatty acid, methane, hydrogen sulfide, tryptophan metabolites and by abnormal bile acid biotransformation. It has been proven that dysbiotic abnormalities of the intestinal microbiome play a role in the pathophysiology of constipation, which allows for the use of prebiotics, probiotics, and synbiotics for effective microbiome-modulating therapy in patients with chronic constipation. The proven role of dysbiotic abnormalities of the intestinal microbiome in the pathophysiology of chronic constipation determines the effectiveness of microbiome-modulating therapy (prebiotics, probiotics, synbiotics) in patients with this syndrome.

Inulin is the most studied preboitic; it is a soluble food fiber that markedly contributes to the regulation of intestinal microbiota, stimulates the growth of beneficial bacteria, and production of anti-inflammatory metabolites. Inulin normalized the intestinal function in patients with chronic constipation increasing the stool frequency, softening the stool, and reducing the intestinal transit time. In addition, inulin modulates the immune response and impacts the absorption of minerals, appetite, and satiety.

Treatment with probiotics is also associated with reduced intestinal transit time, compared to controls. According to a systematic review and meta-analysis of 30 randomized controlled trials, only Bifidobacterium lactis strains (but not other probiotics) significantly increase stool frequencies in chronic constipation in adults. Clinical studies have shown that the targeted probiotic Bifidobacterium lactis HN019 can significantly increase the stool frequencies in patients with low (≤ 3 per week) stool frequency up to 4.7–5.0 per week, reduce the intestinal transit time and the rate of functional gastroenterological symptoms in adults with constipation. Beyond its clinical effects, Bifidobacterium lactis HN019 leads to beneficial changes in intestinal microbiota, significantly increasing the bifidobacteria and decreasing the enterobacteria numbers.

The results of trials confirm the importance of synbiotic correction of dysbiotic microbiota in all patients with constipation to increase stool frequencies and improve fecal consistency, as well as to prevent the chronic disorders associated with constipation. Synbiotics, such as a combination of Bifidobacterium lactis HN019 and inulin, with the properties of both complementary and synergic synbiotic, may have the greatest microbiome-modulating and functional potential to significantly improve clinical outcomes in patients with chronic constipation compared to probiotics or prebiotics used alone.

Almanac of Clinical Medicine. 2024;52(5):280-296
pages 280-296 views

CLINICAL CASES

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

Binyakovskiy R.V., Borisovskaya S.V., Zaharov O.D., Kiselev D.G., Lepkov S.V., Melekhov A.V., Nikitin I.G., Salikov A.V.

Abstract

We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis.

An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes.

The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Almanac of Clinical Medicine. 2024;52(5):297-306
pages 297-306 views

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