Trends in oesophageal cancer mortality in Montenegro, 1990-2018.

BACKGROUND: Oesophageal cancer (OC) is a significant public health issue, despite the decreasing trends in OC mortality rates observed globally in the past decades. The objective of our study is to analyze the pattern of OC mortality in Montenegro between 1990 and 2018 and contribute to the development of a national long-term strategy for the prevention and control of this malignancy. METHODS: The data on OC death cases in Montenegro between 1990 and 2018 were collected. The mortality rates were standardized according to the World Standard Population. The Joinpoint, Linear and Poisson regressions were applied to analyze the OC mortality trend. RESULTS: Joinpoint regression analysis showed an increase in death rates for men and the overall level which were not statistically significant. However, the number of cases increases significantly with an average annual percentage change (AAPC) increase of 2.6% for the overall level [AAPC (95% CI)=2.6 (1.0-4.2); P = 0.002] at the expense of the increase in men, which on average was 2.6% annually [AAPC (95%CI) = 2.6 (1.2-4.1); P = 0.001]. The age groups 55-64 and 65-74 have the highest percentage of deaths cases from OC with 30.6% and 31.4%, respectively. CONCLUSION: Montenegro has witnessed a recent increase in the number of deaths from OC, although the mortality rates remain stable. National strategies to further reduce mortality rates for OC are necessary. Individuals aged 55-64 and 65-74 need specific attention during the ongoing monitoring of this cancer.

Time trends in liver cancer mortality rates in Montenegro from 1990 to 2018.

OBJECTIVE: Liver cancer is the third most common cause of cancer-related deaths worldwide. Hepatitis B and C infections are the main factors affecting mortality. During recent years, Montenegro conducted activities on eradication of viral hepatitis according to the global strategy for the primary prevention of liver cancer mortality. The objective of this study was to assess the liver cancer mortality trend in Montenegro for the period of 1990-2018 using regression techniques. METHODS: liver cancer mortality data in Montenegro from 1990 to 2018 were collected. Mortality rates were age standardized to the World Standard Population. The joinpoint, linear and Poisson regressions were used to assess liver cancer mortality trends both overall and gender specific. RESULTS: The mortality trend was constant, with no significant increase or decrease in mortality rates both at the overall level and by gender. The number of cases, however, increases significantly at the overall level by an average of 1.4% per year [average annual percentage change (AAPC) (95% confidence interval, CI): 1.4 (0.5-2.3); P  = 0.004] and in women by 1.9% per year [AAPC (95% CI): 1.9 (0.8-3.1); P  = 0.002]. In men, there was no change in the number of cases. The three age groups most burdened by mortality from liver cancer were 65-74 (34.9%), 75-84 (26.6%) and 55-64 (25.8%). CONCLUSION: The consistent implementation of prevention measures and hepatitis virus infection treatment has played a role in partially favorable liver cancer mortality trends in Montenegro. It is crucial to closely monitor guidelines for this cancer and give particular attention to the elderly population as the most affected.

Trends in gastric cancer mortality in Montenegro, 1990 - 2018: joinpoint regression.

Background Gastric cancer (GC) remains a significant global public health problem, despite the decreasing trends in GC mortality rates in the last five decades. Our study aimed to examine the pattern of GC mortality in Montenegro between 1990 and 2018 and to contribute to the future designing a national long-term strategy for the control and prevention of GC. Methods Gastric cancer mortality data in Montenegro from 1990 to 2018 were collected. Mortality rates were age-standardized to the World Standard Population for estimating both the overall and gender-specific trends. The joinpoint regression model was used to assess GC mortality and identified significant changes in the linear time trend. Linear and Poisson regressions were also applied for additional trend analyses. Results Joinpoint regression reveals a statistically significant decrease in the age-standardized rate for the overall level, on average by 1.4% per year (AAPC (95% IP)= -1.4 (-2.4)-(-0.4); P= 0.007), which was due to a decrease in the age-standardized rate in men with an average annual change of -1.8% (AAPC (95% IP)= -1.8 (-2.9)-(-0.6); P=0.003), while in women the rates were stable (p=0.565). The results for age groups indicate that a decline was registered at the overall level, and among men, as a consequence of the trend of decreasing age-specific rates for the age group 55-64 on average annually by 2% among men (AAPC (95% IP)= -2 ((-3.8)-(-0.1)); P=0.035), and for the overall level (AAPC (95% IP)= -2 ((-3.7)-(-0.3)); P=0.026). Conclusions Our findings indicate a noteworthy decline in age-standardized overall GC mortality rates among men in Montenegro, while rates for women have remained constant. National strategies to further reduce mortality rates for GC are necessary.

The Relationship between Diabetes Mellitus and Pancreatic Cancer-Diabetes Mellitus as a Red Flag for Pancreatic Cancer.

The relationship between diabetes mellitus (DM) and pancreatic cancer is complex-DM is both a risk factor and early sign of pancreatic cancer. DM is a risk factor for pancreatic cancer because it increases insulin resistance, intrapancreatic concentrations of insulin, and the bioavailability of IGF, subsequently promoting ductal cell proliferation. Accordingly, treatment targeting the insulin/IGF pathway is the focus of many researchers. Antidiabetic drugs modify the risk for pancreatic cancer-metformin's antineoplastic effect being most notable and indicating potential clinical use in pancreatic cancer. New-onset DM can also be the first manifestation of pancreatic cancer. There are several theories for the pathogenesis of DM in pancreatic cancer, the most important being that DM is a paraneoplastic syndrome caused by diabetogenic factors. As a consequence of this intricate relationship, new-onset DM after the age of 50 is considered a red flag for pancreatic cancer, prompting the need for screening in this patient population. Multiple clinical studies are currently underway exploring this matter. A better understanding of the relationship between DM and pancreatic cancer could aid in developing novel screening and treatment strategies for pancreatic cancer. This could ultimately improve the prognosis and quality of life of patients with pancreatic cancer.

Diagnosis and treatment of mediastinal ectopic thyroid tissue with normally located thyroid gland and primary hyperparathyroidism: a case report.

Mediastinal ectopic thyroid tissue (ETT) is rare entity, accounting for 1% of all mediastinal tumours. A 53-year-old lady, presented with cough and atypical chest pain. A computed tomography (CT) scan of chest showed a 95 mm × 75 mm × 115 mm tumour mass; CT guided biopsy of mediastinal mass showed ETT. Thyroid scintigraphy with Technetium-99m (99mTc) pertechnetate showed homogenous and intense uptake in the thyroid gland (TG) lodge and in the mediastinum. Primary hyperparathyroidism (PHPT) was diagnosed during laboratory evaluation. Technetium-99m sestamibi (99mTc-MIBI) parathyroid scintigraphy with single photon emission CT (SPECT)/CT showed uptake of radionuclide in two locations, one in the eutopic position [right inferior parathyroid gland (PTG)] and second ectopic (mediastinal). After surgery, histopathological examination confirmed mediastinal ETT and two PTG adenomas. During follow-up, laboratory analyzes were maintained within the reference range and the patient remained stable and free of symptoms and clinical signs, which supports a good prognosis. The existence of an ectopic mediastinal thyroid and an ectopic parathyroid tissue may be partly explained by a similar embryological origin. Diagnosis of ectopic thyroid and parathyroid tissues is demanding; requires a multidisciplinary team and approach using highly accurate radiological and nuclear imaging. The simultaneous existence of mediastinal ETT, nodular eutopic TG and PHPT for which two adenomas are responsible (cervical eutopic and mediastinal ectopic) is a complex diagnostic and therapeutic challenge, which we have described so far as unique. Comprehensive and multidisciplinary surgery planning is a cornerstone of treatment, when recommendations in guidelines are lacking.

First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19.

BACKGROUND AND AIMS: Tocilizumab (TCZ; interleukine-6 receptor antagonist) has been proposed to treat severe forms of Coronavirus disease-19 (COVID-19) because interleukine-6 plays an important role in COVID-19-induced cytokine storm. Several clinical studies have shown very good effects of TCZ in patients with COVID-19, with a few minor side effects reported. Only eight serious liver injuries caused by TCZ were reported before being used in the treatment of patients with COVID-19. Considering the significantly increased use of TCZ for the treatment of COVID-19, we would like to warn of its rare but possible serious hepatotoxicity, especially when used together with other hepatotoxic drugs. METHODS: We describe a patient with COVID-19-induced cytokine storm who developed drug-induced liver injury associated with the use of TCZ. RESULTS: One day after TCZ administration, serum transaminase levels increased 40-fold. Nevertheless, TCZ had a positive effect on clinical and laboratory parameters in cytokine storm, with transaminases values normalizing in 10 days. CONCLUSIONS: This is the first reported case of DILI caused by TCZ in a COVID-19 patient. Intensive liver function monitoring is imperative in COVID-19 patients, because of frequent polypharmacy with potentially hepatotoxic drugs.

Pregnancy-Induced Sweet's Syndrome Treated with Infliximab.

OBJECTIVE: To present a case of relapsing and resistant Sweet's syndrome that developed during pregnancy together with an onset of Crohn's disease, showing complete resolution with the use of infliximab. CLINICAL PRESENTATION AND INTERVENTION: A 30-year-old pregnant woman presented with fever, skin lesions, and diarrhea. Skin biopsy confirmed neutrophilic dermatosis and she was diagnosed with Crohn's disease after endoscopy. There was no recurrence of Sweet's syndrome outside of her pregnancy. During a previous pregnancy, while corticosteroids were ineffective, complete regression of skin lesions was achieved using infliximab. CONCLUSION: The "off-label" use of infliximab is beneficial for relapsing and resistant Sweet's syndrome.

Nonsteroidal Anti-Inflammatory Drug-Induced Colopathy in a Colorectal Cancer Screening Program.

OBJECTIVE: To present a case of colopathy related to the use of diclofenac in a patient with a positive immunochemical faecal occult blood test (iFOBT) and to discuss the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on iFOBT specificity. CLINICAL PRESENTATION AND INTERVENTION: A colonoscopy in a 56-year-old female presenting with a positive iFOBT revealed diaphragm-like strictures and ulcers in the right colon. While carrying out a detailed retrospective interview, she reported a chronic backache requiring long-term NSAID treatment. CONCLUSION: No association has been established between chronic use of NSAID and a false-positive iFOBT. There is no need to stop NSAIDs before performing an iFOBT in a colorectal cancer screening program.

Renal aspergillosis in a liver transplant patient: A case report and review of literature.

BACKGROUND: Aspergillosis is a frequent invasive fungal infection in liver recipients (affecting 1%-9.2% of all patients), second only to candidiasis. Significant risk factors for invasive aspergillosis in liver recipients include corticosteroid therapy, neutropenia, T-cell dysfunction, renal failure and requirement for renal replacement therapy. Aspergillus infection usually affects the lungs of liver recipients, with hematogenous dissemination occurring in 50%-60% of cases. Renal involvement is rare and is considered to occur in 0.4% of all cases of invasive aspergillosis. CASE SUMMARY: This paper describes a case of a liver recipient presenting with a newly formed renal mass a year after liver transplantation. The patient underwent liver transplantation due to alcoholic liver cirrhosis, with preoperative corticosteroid therapy and postoperative immunosuppressants (tacrolimus and mycophenolate mofetil). His 1-year follow-up was uneventful, with a satisfying graft function and lack of any symptoms. During a routine follow-up abdominal ultrasound, he was diagnosed with a renal tumor. The renal imaging findings were inconclusive (with a differential diagnosis to renal cell carcinoma), while the computed tomography (CT) of the chest showed scar tissue in the lungs suggestive of previous inflammation. The patient underwent radical nephrectomy, with histopathological analysis showing renal aspergilloma, yielding postoperative treatment with voriconazole. His follow up was uneventful, and the chest CT did not show any change in pulmonary lesions. This case illustrates the possibility of aspergillosis affecting the lungs of liver recipients, subsequently affecting the kidney and forming an aspergilloma. CONCLUSION: Clinicians should be aware of aspergilloma mimicking solid organ tumors in organ recipients.

Colorectal cancer screening in a low-incidence area: general invitation versus family risk targeting: a comparative study from Montenegro.

OBJECTIVES: Colorectal cancer (CRC) is one of the most common malignancies worldwide. The aim of this study was to compare the outcomes of two different screening approaches in a small country (Montenegro, 650,000 inhabitants) with a CRC incidence lower than the European average. METHODS: Two structured invitation programs were compared with respect to compliance and neoplasia yield: (i) program A focused on first-degree relatives of CRC patients diagnosed in two hospitals (n=206), inviting them for colonoscopy; (ii) program B was an invitation program for fecal occult blood testing, followed by colonoscopy if positive, conducted in University Hospital, Podgorica, Montenegro, on 2760 randomly selected average-risk persons, age 50-74 years, living in a single municipality. RESULTS: Of 710 first-degree relatives of 206 CRC patients approached, 540 presented for colonoscopy (76.05% uptake). Overall, 31 were diagnosed with a cancer, 58 with advanced adenoma, and 151 with adenoma in general. In the general screening program, of 2760 individuals invited, 920 underwent fecal immunochemical test (33.3% uptake) and colonoscopy was performed in all 95 positive cases (10.3%); six cancers was found in five patients (one patient had two cancers), 19 patients were diagnosed with advanced adenoma, and 26 with any adenomas. The risk-targeted screening program had a significantly higher yield for cancers in both per invited (31/710 vs. 5/2760, P<0.001) and per eligible person analysis (31/540 vs. 5/920, P<0.001). CONCLUSION: In a low-incidence country with limited resources, it may be advisable to start with CRC screening targeted to risk groups.

Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection and without exposure to non-steroidal anti-inflammatory drugs.

BACKGROUND/AIM: A high risk of bleeding in Helicobacter pylori (H. pylori)-negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. METHODS: A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs and proton pump inhibitors (PPI) within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF) and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI). RESULTS: Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509) and exposure to stress (p = 0.944). Aspirin was used by 16/48 (33.3%) patients with bleeding ulcer, as opposed to 7/47 (14.9%) patients who did not bleed (p = 0.036). Abnormal platelet function had 12/48 (25.0%) patients who bled, as opposed to 2/47 (4.3%) patients who did not bleed (p = 0.004). Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023). There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.20%) patients with bleeding ulcer and in only 5/47 (10.6%) patients who had ulcer without bleeding (p = 0.024). CONCLUSION: Abnormal platelet function, aspirin use and antrum atrophy were the risk factors for ulcer bleeding in non-H. pylori, non- NSAIDs ulcer disease.

Role of Helicobacter pylori infection in gastroduodenal damage in patients starting NSAID therapy: 4 Months follow-up study.

AIMS: We aimed to determine differences in gastroduodenal damage related to the presence of Helicobacter pylori (Hp) in patients starting long-term NSAID therapy. Seventy-one candidates for chronic NSAIDs therapy (33 Hp negative and 38 Hp positive) entered the study and underwent upper GI endoscopy before, and 8 and 16 weeks after, continuous NSAID therapy. RESULTS: Lanza score increased in both Hp positive and negative patients in the course of NSAID therapy (P < 0.001), being significantly higher in Hp positive than Hp negative (4.31 ± 1.33 vs 3.15 ± 1.95, P < 0.05) after 16 weeks of follow-up. In gastric mucosa, no significant difference in mean Lanza score was observed between the two groups. Duodenal ulcer was diagnosed in 18 (36.8%) Hp positive and 1 (3%) Hp negative patient (P < 0.05). CONCLUSIONS: Hp is more closely related to duodenal than gastric mucosal injury in NSAID users. Risk for duodenal ulcer in Hp-infected individual increases after 4 months of NSAID therapy.