Utility of endoscopic ultrasound in idiopathic acute recurrent pancreatitis.

Idiopathic acute recurrent pancreatitis (IARP) is defined as at least two episodes of acute pancreatitis with the complete or near-complete resolution of symptoms and signs of pancreatitis between episodes, without an identified cause. There is a paucity of information about the usefulness of endoscopic ultrasound (EUS) in IARP. OBJECTIVES: To determine the diagnostic yield of EUS in IARP. DESIGN: A retrospective study was performed in patients with IARP evaluated by EUS between January 2009 and December 2016. Follow-up assessments of acute pancreatitis recurrence were carried out. RESULTS: Seventy-three patients with 102 EUS procedures were included. EUS was able to identify the cause of IARP in 55 patients (75.3%). The most common findings were chronic pancreatitis in 27 patients (49.1%), followed by lithiasic pathology in 24 patients (43.6%), and intraductal papillary mucinous neoplasm in four patients (7.3%). A directed treatment against EUS findings had a protective tendency associated with the final resolution of recurrence. There were no complications reported. CONCLUSION: EUS performed in patients with IARP helped to identify a possible cause in 2/3 of the cases. The majority of patients have a treatable disease.

Pancreatogenic Diabetes, 2 Onset Forms and Lack of Metabolic Syndrome Components Differentiate It From Type 2 Diabetes.

OBJECTIVES: We compared pancreatogenic (DM3c) and type 2 diabetes mellitus. METHODS: We compared age-, sex-, and diabetes mellitus duration-matched DM3c cases (n = 142) and type 2 diabetes mellitus (n = 142). Pancreatogenic diabetes was considered when it appeared after the diagnosis of pancreatitis or after pancreatic surgery. RESULTS: Pancreatogenic diabetes presented lower body mass index (BMI) [odds ratio (OR), 1.2; 95% confidence interval (CI), 1.13-1.28; P < 0.001], worse glycemic control (OR, 1.196; 95% CI, 1.058-1.35; P = 0.004), required insulin more frequently (OR, 4.21; 95% CI, 2.57-6.93; P = 0.0001), had more hypoglycemic episodes (OR, 3.65; 95% CI, 1.64-8.16; P = 0.001) but lower frequency of dyslipidemia (OR, 0.42; 95% CI, 0.26-0.68; P = 0.001) and arterial hypertension (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01). Pancreatogenic diabetes cases on pancreatic enzyme replacement therapy had lower glycosylated hemoglobin (8.52% vs 9.44%; P = 0.026), serum carotenes (79.1 vs 116.1; P = 0.03), and BMI (23.4 vs 26.1; P = 0.0005) than those not on pancreatic enzyme replacement therapy. Pancreatogenic diabetes onset occurred earlier in necrotizing pancreatitis and after pancreatic surgery. CONCLUSIONS: Pancreatogenic diabetes presents with low BMI and lacks metabolic syndrome components. The type of pancreatic disease or surgery defines its onset time.

A Nondilated Main Pancreatic Duct Predicts Type 2 Autoimmune Pancreatitis: Comparative Study of Resected Pancreatic Head Masses.

BACKGROUND: Chronic pancreatitis (CP), pancreatic cancer (PCa), and autoimmune pancreatitis (AIP) often present as a pancreatic mass. Accurate diagnosis is not always possible; up to 8% of surgical procedures are performed in benign pancreatic masses presumed to be malignant. OBJECTIVES: We aimed to compare clinical and imaging characteristics of resected focal type 2 AIP, CP, and PCa and identify factors that could improve preoperative differential diagnosis. METHODS: Charts from patients that underwent pancreatic resection under suspicion of PCa between 2000 and 2014 were reviewed. Clinical and imaging data were recorded. Subjects were grouped as type 2 AIP, CP, and PCa. RESULTS: We included 79 cases; 41 men, mean age of 57.3 years/old ± 15.6 SD. Pathology report was type 2 AIP (20%), CP (10%), and PCa (70%). According to international consensus criteria for AIP 11 cases were deemed probable type 2 and 5 as unspecific pancreatic mass. A nondilated main pancreatic duct (MPD) was associated with AIP (OR 9.3; 95% CI 3.05-28.7), p < 0.001; obstructive jaundice (OR 28.5; 95% CI 8.18-79.5); and a dilated MPD (OR 5.21; 95% CI 1.9-14.6) suggested malignancy. CONCLUSIONS: In the setting of undetermined pancreatic focal mass, a nondilated MPD suggests the diagnosis of type 2 AIP.

Increased Mortality from Extrapancreatic Infections in Hospitalized Patients with Acute Pancreatitis.

Nosocomial extrapancreatic infections in patients with acute pancreatitis (AP) are associated with a higher mortality even after adjusting the risk for the severity of the pancreatitis. The aim of this study was to describe the clinical features of hospitalized patients with AP who died during their hospitalization and to evaluate risk factors associated with mortality. We performed a descriptive study of the clinical features of adult patients who died from AP during their hospitalization and a case control study with a paired group of patients that survived AP during a 10-year period. Data of interest were collected from the medical records and are presented with appropriate measures of central tendency and dispersion. For the case control study, the primary outcome evaluated was death, and to evaluate associated clinical features and determine differences between groups, we performed the χ 2 or Fisher's exact tests for categorical variables and the Student t-test or Mann-Whitney U test for continuous variables as appropriate. We found 48 patients with acute pancreatitis who died within the period of the study during hospitalization; from these, 50% were men, mean age was 53.2 years, and the most common etiology was biliary obstruction by gallstones in 45.8%. The global mortality rate was of 2.5%. A total of 43.7% patients had infected pancreatic necrosis, and in 58.3%, some extrapancreatic infection was documented, being the most common urinary tract infection in 50%, bacteremia in 50% and pneumonia in 33.3%. Clinical features associated with mortality were the presence of organ failure (p < 0.001), nosocomial complications (p < 0.001), infected necrosis (p < 0.001), and extrapancreatic infections (p = 0.002). From the different extrapancreatic infections, only bacteremia (p = 0.001) and pneumonia (p = 0.011) were associated with higher mortality. In conclusion, extrapancreatic infections are associated with increased mortality among hospitalized patients with acute pancreatitis, in particular, bacteremia and pneumonia with an isolated pathogen.

Retroperitoneal fibrosis. Steroid treatment response seems to depend on its association to IgG4 related disease.

Retroperitoneal fibrosis (RF) is part of a rare fibrosclerotic disorder. Oral steroids are the initial treatment. Steroid combination with other immunosupressants is used in refractory cases. Steroids refractoriness has been observed in chronic cases. Some cases of RF represent a manifestation of the IgG4 related disease (IgG4-RD) that is associated to a dramatic response to steroid therapy. It is uncertain if RF́s treatment response differs according to its association with IgG4-RD. We hypothesize that RF́s treatment response to steroids depends on the association with IgG4-RD, thus, we collected and compared clinical data from 10 RF cases; 6 male, mean age 50.6 (±16.15 SD) years. Mean FU was 28 (±25.7 SD) months. According to IgG4 levels, patients were categorized as idiopathic RF (IRF n = 5) or RF-IgG4-RD (n = 5). Therapy response was categorized as complete, partial, stable disease, recurrence or non-response. Nine cases received initial therapy with prednisone; complete response was achieved in 4 RF-IgG4 RD. The remaining 5 cases (1 RF-IgG4RD and 4 IRF) underwent a 2nd line therapy; 4 prednisone + tamoxifen and 1 prednisone + azathioprine. Prednisone + tamoxifen combination achieved complete response in 1 case (RF-IgG4RD), partial response in 1 IRF; in 1 IRF case, disease remained stable and 1 did not respond. The prednisone + azathioprine treatment achieved complete response. At follow-up all patients remained stable and no recurrence was registered. These observations suggest and support the hypothesis that response to steroid monotherapy depends on the association of RF with IgG4, suggesting that IRF cases might benefit from initial combination therapies instead of steroid monotherapy.

Abnormal Cardiovascular Findings in Acute Pancreatitis: Are They Associated with Disease Severity?

BACKGROUND: Acute pancreatitis (AP), a disease that commonly requires in-hospital treatment, has been associated with a high incidence of abnormal cardiovascular findings (ACFs). We conducted a prospective study to explore the association of these findings with severity of the disease. METHODS: Adult patients with AP diagnosis were prospectively enrolled in an observational study during an 8-month period in a tertiary care center. AP and its severity were defined according to the Revised Atlanta Classification of AP. Subjects were submitted to electrocardiographic, echocardiographic, and serologic testing during the acute period and a 3-month follow-up. The incidence of ACF was compared between two groups: (1) Mild and (2) moderate/severe cases. RESULTS: Twenty-seven patients (mean age 48 ± 17 years) with AP were enrolled; 15 (55%) had mild and 12 (45%) had moderate/severe AP. During the acute episode, 67% had increased pro-brain natriuretic peptide levels; 52% had abnormal electrocardiographic findings; 48% had abnormal echocardiographic findings; and 18% had increased troponin I levels. There was no significant difference in the incidence of ACF between mild and moderate/severe groups. Nineteen patients (70%) had repeated follow-up testing, and most of the initial ACF did not persist. CONCLUSION: ACFs occur in an important proportion of patients during AP episodes. Future research should continue to focus in the association of ACFs and the severity of the disease.

EUS-guided drainage of pancreatic pseudocysts offers similar success and complications compared to surgical treatment but with a lower cost.

BACKGROUND AND AIM: Pancreatic pseudocysts (PPC) are a complication that occurs in acute and chronic pancreatitis. They comprise 75% of cystic lesions of the pancreas. There are scarce data about surgical versus endoscopic treatment on PPC. The aim of this study was to compare both treatment modalities regarding clinical success, complication rate, recurrence, hospital stay and cost. METHODS: Retrospectively, data obtained prospectively from 2000 to 2012 were analyzed. A PPC was defined as a fluid collection in the pancreatic or peripancreatic area that had a well-defined wall and contained no solid debris or recognizable parenchymal necrosis. Clinical success was defined as complete resolution or a decrease in size of the PPC to 2 cm or smaller. RESULTS: Overall, 64 procedures in 61 patients were included: 21 (33%) cases were drained endoscopically guided by EUS and 43 (67%) cases were drained surgically. The clinical success of the endoscopic group was 90.5 versus 90.7% for the surgical group (P = 0.7), with a complication rate of 23.8 and 25.6%, respectively (P = 0.8), and a mortality rate of 0 and 2.3% for each group, respectively (P = 0.4). The hospital stay was lower for the endoscopic group: 0 (0-10) days compared with 7 (2-42) days in the surgical group (P < 0.0001). Likewise, the cost was lower in the endoscopic group (P < 0.001). The recurrence rate was similar in both groups: 9.5 and 4.5% respectively (P = 0.59). The two recurrences found in the endoscopic group were associated with stent migration, and the recurrence in the surgical group was due to the type of surgery performed (open drainage). CONCLUSION: Endoscopic treatment of PPC offers the same clinical success, recurrence, complication and mortality rate as surgical treatment but with a shorter hospital stay and lower costs.

Decrease in the Prevalence of Pancreatitis Associated with Primary Hyperparathyroidism: Experience at a Tertiary Referral Center.

BACKGROUND: Hypercalcemia is a rare but well recognized cause of acute and chronic pancreatitis. Hypercalcemia-related pancreatitis is mainly caused by primary hyperparathyroidism. The prevalence of pancreatitis in hyperparathyroidism varies worldwide and additional disease-modifying factors may play a role in its development. In 1988 the prevalence of pancreatitis secondary to primary hyperparathyroidism at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), a referral center in Mexico City, was 12.1% (95% CI: 6.7-21). OBJECTIVE: To describe the current prevalence of pancreatitis secondary to primary hyperparathyroidism at the INCMNSZ. METHODS: We reviewed 385 cases of primary hyperparathyroidism seen at the hospital between 1987 and 2012. RESULTS: 26 cases with acute or chronic pancreatitis associated with primary hyperparathyroidism were documented, with a prevalence of 6.7% (95% CI: 4.6-9.7), which was lower than the 12.1% previously reported. In the present study, 20% had a history of alcohol consumption, 10% of gallstones, and 20% of ureteral calculi, compared with the previously reported 32.0, 34.6, and 40.0%, respectively. The average calcium levels were 13.1 and 13.8 mg/dl in the previous and current series, respectively. CONCLUSIONS: We found a decrease in the prevalence of pancreatitis associated with primary hyperparathyroidism from 12.1% (95% CI: 6.7-21) to 6.7% (95% CI: 4.6-9.7).

Diagnostic yield of endoscopic ultrasound in patients with hypoglicemia and insulinoma suspected.

BACKGROUND AND OBJECTIVES: Noninvasive imaging techniques have shown limitations to identify insulinomas. In few studies reported so far, endoscopic ultrasound (EUS) has proven to be able to locate lesions. The aim of this study was to compare the performance of computed tomography versus EUS for the detection of insulinomas. MATERIALS AND METHODS: In a retrospective manner prospectively collected data were analyzed. Patients with hypoglucemia and hyperinsulinemia were included. Diagnostic yield was measured in relationship to sensitivity, specificity, positive predictive value, negative predictive value and accuracy. Surgical specimens were considered the gold standard. RESULTS: Sensitivity, positive predictive value, and accuracy of EUS was 100%, 95.4% and 95.4%, respectively. In the case of CT the sensitivity was 60%, specificity 100%, positive predictive value 100%, negative predictive value 7%, and accuracy were 68%. CONCLUSIONS: EUS is useful in the preoperative assessment of patients with hypoglycemia and serum hyperinsulinemia.

Serous Cystadenomas Follow a Benign and Asymptomatic Course and Do Not Present a Significant Size Change During Follow-Up.

BACKGROUND: Serous cystadenoma is a benign pancreatic cystic neoplasm. Conservative management is favored. We studied the clinical characteristics and course of serous cystadenoma in patients undergoing surgery or conservative management only at an academic referral center. METHODS: Patients presenting with serous cystadenoma in the years 2000-2013 were selected. Hospital records were evaluated for patient and serous cystadenoma characteristics. RESULTS: A total of 22 patients with serous cystadenoma were identified. Mean age at diagnosis was 63 years and 82% were women. Diagnosis was incidental in 59%, and 18% presented with unspecific abdominal pain, 14% unexplained weight loss, 4.5% gastrointestinal obstructive symptoms, and 4.5% cholangitis. Location was pancreas body 36%, head 32%, tail 23%, and uncinate 9%. Mean serous cystadenoma diameter at diagnosis was 37 ± 23 mm. After diagnosis five patients underwent surgery. Initial size was similar between surgical and follow-up groups (p = 0.9). Four cases were lost to follow-up; 13 continued conservative management with a mean follow-up time of 54 ± 27 months. The initial and last serous cystadenoma size in the follow-up group remained similar (p = 0.9). Six cases presented significant tumor growth during follow-up (p > 0.05). All patients remained asymptomatic throughout follow-up. No malignancy or serous cystadenoma-related death occurred. CONCLUSIONS: Size change of serous cystadenoma was minimal and patients remained asymptomatic during follow-up. Surgery should be limited to symptomatic and selected cases.

Follow-up of patients with pseudotumoral chronic pancreatitis: outcome and surveillance.

AIM: To follow up patients with pseudotumoral chronic pancreatitis (PCP) to assess their outcome and identify an optimal surveillance interval. METHODS: Data obtained prospectively were analyzed in a retrospective manner. Patients with clinical evidence of chronic pancreatitis (abdominal pain in the epigastrium, steatorrhea, and diabetes mellitus), endoscopic ultrasound (EUS) criteria > 4, and EUS-fine needle aspiration (FNA) were included. A pseudotumor was defined as a non-neoplastic space-occupying lesion, a cause of chronic pancreatitis that may mimic changes typical of pancreatic cancer on CT or endoscopic ultrasound but without histological evidence. A real tumor was defined as a neoplastic space-occupying lesion because of pancreatic cancer confirmed by histology. RESULTS: Thirty-five patients with chronic pancreatitis were included, 26 (74.2%) of whom were men. Nine (25.7%) patients were diagnosed with pseudotumoral chronic pancreatitis and two (2/35; 5.7%) patients with pseudotumoral chronic pancreatitis were diagnosed with pancreatic cancer on follow-up. The time between the diagnosis of pseudotumoral chronic pancreatitis and pancreatic adenocarcinoma was 35 and 30 d in the two patients. Definitive diagnosis of pancreatic adenocarcinoma was made by surgery. In the remaining six patients with pseudotumoral chronic pancreatitis, the median of follow-up was 11 mo (range 1-22 mo) and they showed no evidence of malignancy on surveillance. In the follow-up of patients without pseudotumoral chronic pancreatitis but with chronic pancreatitis, none were diagnosed with pancreatic cancer. According to our data, older patients with chronic pancreatitis are at risk of pseudotumoral chronic pancreatitis. CONCLUSION: According to characteristics of patient, detection of PCP should lead a surveillance program for pancreatic cancer with EUS-FNA in < 1 mo or directly to surgical resection.

[Immunoglobulin G4-associated to multiorganic lymphoproliferative disease]. / Enfermedad linfoproliferativa multiorgánica asociada a inmunoglobulina G4.

We report a case of a woman with lymphoproliferative multiorganic immunoglobulin G4 (IgG4) related disease with extensive involvement showing dacryoadenitis, sialoadenitis, parotiditis, pancreatitis, pneumonitis, lymphadenopathy and immune thrombocytopenic purpura. Serum elevation of acute phase reactant, polyclonal hypergammaglobulinemia, positivity for antinuclear antibodies and rheumatoid factor was found. Hystologically plasma cell infiltration was demonstrated on glandular and lymphatic tissue and immunochemistry was positive for IgG4 in > 30%. Immunosuppressive treatment with steroids and azathioprine was given with an excellent clinical response, the marked radiologic evidence of improvement and the decrease in inflammatory makers that conducted to symptom remission are shown in the text.

Bacterial meningitis in cirrhotic patients: case series and description of the prognostic role of acute renal failure.

AIM: To analyze the mortality risk factors in cirrhotic patients with bacterial meningitis (BM). BACKGROUND: Cirrhotic patients are susceptible to infections. Despite its high mortality rate, BM has not been extensively studied in this group of patients. STUDY: BM patients diagnosed with cirrhosis, between 1987 and 2008, were studied. BM was defined as the presence of signs or symptoms of meningitis and a cerebrospinal fluid (CSF) leukocyte count >100/mm3 or the presence of bacteria in CSF. RESULTS: We identified 4955 infections among 7591 cirrhotic patients; 12 (0.2%) had BM. The mean age at diagnosis was 60±16 years. Abnormal mental status (83%), fever (67%), and neck stiffness (67%) were the most frequent clinical presentations. The sensitivity of CSF culture was 75% (Streptococcus pneumoniae, 2; Staphylococcus aureus, 2; Listeria monocytogenes, 1; Group B Streptococcus, 1; Streptococcus agalactiae, 1; Streptococcus bovis, 1; and Escherichia coli, 1), and its correlation with blood culture was 78%. Five patients died. On admission, the serum creatinine level was 1.63±0.93 mg/dL. A serum creatinine level ≥1.3 mg/dL was associated with increased mortality (P=0.028). The model for end-stage liver disease score, gastrointestinal bleeding, bilirubin level >3.5 mg/dL, hepatic encephalopathy, diabetes mellitus, and results of cytology and biochemistry tests of CSF were not associated with mortality. CONCLUSIONS: BM in cirrhotic patients is associated with a high mortality rate. The clinical and microbiologic features of BM in cirrhotic patients differ from those in the general population. A serum creatinine level ≥1.3 mg/dL on admission is associated with a higher risk of mortality.

Growth factors as treatment for inflammatory bowel disease: a concise review of the evidence toward their potential clinical utility.

In the process of inflammation and repair of the intestinal mucosa in inflammatory bowel disease (IBD), there occurs a complex and an unknown interplay of innate and adaptive immune mechanisms. This interaction of factors may explain why IBD is characterized by a relapsing and remitting clinical course. Different components of innate immunity, hormones and interleukins in IBD have been suggested to be impaired. The growth hormone, epidermal growth factor, keratinocyte growth factor and colony-stimulating factors have emerged as potential tools for the modulation of intestinal inflammation and repair. Despite promising results of initial studies, the evidence that justify treatment of patients in clinical practice is not enough as some of the trials are nonrandomized or included a small number of patients. In this concise review, we provide a summary of the most recent and relevant evidence regarding the potential therapeutic effects of growth factors in IBD.

Marcadores serológicos en enfermedadinflamatoria intestinal: diferenciaspoblacionales y limitaciones de suaplicación / Serological markers in inflammatory bowel

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Image-guided percutaneous procedure plus metronidazole versus metronidazole alone for uncomplicated amoebic liver abscess.

BACKGROUND: Metronidazole is the standard of care for uncomplicated amoebic liver abscesses (considering that complicated liver abscesses are those localized in left lobe, multiple, and/or pyogenic abscesses). However, a subset of patients with amoebic liver abscesses remain symptomatic, with a significant risk of rupture of the abscess into the peritoneum. The role of image-guided percutaneous therapeutic aspiration in these patients remains controversial. OBJECTIVES: To assess the beneficial and harmful effects of image-guided percutaneous procedure plus metronidazole versus metronidazole alone in patients with uncomplicated amoebic liver abscess. SEARCH STRATEGY: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2007), MEDLINE (1966 to November 2007), EMBASE (1988 to September 2007), and Science Citation Index Expanded (1945 to September 2007). SELECTION CRITERIA: Randomised or quasi-randomised trials comparing an image-guided percutaneous procedure plus metronidazole versus metronidazole alone in patients with uncomplicated amoebic liver abscess. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data extraction were done in duplicate. We calculated relative risks (RR) and mean differences, and checked for heterogeneity by visual inspection of forest plots and chi-squared and I(2) tests. MAIN RESULTS: Seven low quality randomised trials were included. All studies included a total of 310 patients, but due to selective outcome reporting bias, less patients could be included in our analyses. Pooled analysis of three homogenous trials showed that needle aspiration did not significantly increase the proportion of patients with fever resolution (RR 0.60, 95% confidence interval (CI) 0.22 to 1.61). Sensitivity analysis according to trial quality preserved these findings. Trials that evaluated resolution of abdominal pain, days to resolution of fever, pain, resolution of abscess cavities, reduction in liver size, and duration of hospitalisation were heterogeneous. The benefits in the number of days to resolution of pain (MD -1.59, 95%CI -2.73 to -0.42), number of days to resolution of abdominal tenderness (MD -1.70, 95%CI -2.86 to -0.54), and duration of hospitalisation (MD -1.31, 95%CI -2.05 to -0.57) were observed in the needle aspiration group only. AUTHORS' CONCLUSIONS: Therapeutic aspiration in addition to metronidazole to hasten clinical or radiologic resolution of uncomplicated amoebic liver abscesses cannot be supported or refuted by the present evidence. The trials lack methodological rigour and adequate sample size to conclude on the presence of effectiveness of adjunctive image-guided aspiration plus metronidazole versus metronidazole alone. Further randomised trials are necessary.

[Critical analysis of awards in gastroenterology research. The Mexican experience]. / Análisis de los premios a la investigación en gastroenterología. Experiencia en México.

The impact of Mexican gastrointestinal research worldwide is limited and the outcome of the best research papers awarded by the Asociación Mexicana de Gastroenterología (AMG) is unknown. The objective of this study was to analyze the publication pattern of the research work, awarded by the AMG and their impact in international journals. The abstracts accepted for the annual meeting of the AMG from 1998 to 2006 were reviewed. Those presented in a plenary session or awarded were included. Their abstracts were searched in electronic databases. When not found, the main author was contacted by e-mail. In those papers published in a journal with an impact factor, the times it was cited were assessed. 35 abstracts were identified, mainly in gastroenterology (57.1%) and hepatology (34.3). Only in 5.7% (n=2) some of the authors were members of the governing board of AMG. The awarded institutions were Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (48.6%), Universities (Universidad Autónoma de Nuevo León, Universidad Nacional Autónoma de México and the Benemérita Universidad Autónoma de Puebla) (31.4%), Instituto Mexicano del Seguro Social (8.6%), Fundación Clínica Médica Sur (5.7%), Hospital Juárez (2.9%), Private hospital (2.9%). Most of the papers were published within a year (73.7%). Only 2 papers had more than 10 citations in another international journal with impact factor, with a median for all paper of 5 citations (0-45). Considering all institutions, the rate of publication is 48%. Only half of the awarded works were published and mainly in journals of local distribution. The impact of these studies worldwide is limited.