Incidence, clinical management and prognosis of patients with small intestinal adenocarcinomas from 1999 through 2019: A nationwide Dutch cohort study.

BACKGROUND: Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. PATIENTS AND METHODS: Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. RESULTS: The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35-0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25-3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36-0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36-0.80)). CONCLUSIONS: The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making.

Nationwide Impact of Centralization, Neoadjuvant Therapy, Minimally Invasive Surgery, and Standardized Pathology Reporting on R0 Resection and Overall Survival in Pancreatoduodenectomy for Pancreatic Cancer.

BACKGROUND: Surgeons aim for R0 resection in patients with pancreatic cancer to improve overall survival. However, it is unclear whether recent changes in pancreatic cancer care such as centralization, increased use of neoadjuvant therapy, minimally invasive surgery, and standardized pathology reporting have influenced R0 resections and whether R0 resection remains associated with overall survival. METHODS: This nationwide retrospective cohort study included consecutive patients after pancreatoduodenectomy (PD) for pancreatic cancer from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database (2009-2019). R0 resection was defined as > 1 mm tumor clearance at the pancreatic, posterior, and vascular resection margins. Completeness of pathology reporting was scored on the basis of six elements: histological diagnosis, tumor origin, radicality, tumor size, extent of invasion, and lymph node examination. RESULTS: Among 2955 patients after PD for pancreatic cancer, the R0 resection rate was 49%. The R0 resection rate decreased from 68 to 43% (2009-2019, P < 0.001). The extent of resections in high-volume hospitals, minimally invasive surgery, neoadjuvant therapy, and complete pathology reports all significantly increased over time. Only complete pathology reporting was independently associated with lower R0 rates (OR 0.76, 95% CI 0.69-0.83, P < 0.001). Higher hospital volume, neoadjuvant therapy, and minimally invasive surgery were not associated with R0. R0 resection remained independently associated with improved overall survival (HR 0.72, 95% CI 0.66-0.79, P < 0.001), as well as in the 214 patients after neoadjuvant treatment (HR 0.61, 95% CI 0.42-0.87, P = 0.007). CONCLUSIONS: The nationwide rate of R0 resections after PD for pancreatic cancer decreased over time, mostly related to more complete pathology reporting. R0 resection remained associated with overall survival.

Clinical implications of chyle leakage following esophagectomy.

The clinical consequences of chyle leakage following esophagectomy are underexposed. The aim of this study was to investigate the clinical implications of chyle leakage following esophagectomy. This retrospective study of prospectively collected data included patients who underwent transthoracic esophagectomy in 2017-2020. Routinely, the thoracic duct was resected en bloc as part of the mediastinal lymphadenectomy. Chyle leakage was defined as milky drain fluid for which specific treatment was initiated and/or a triglyceride level in drain fluid of ≥1.13 mmol/L, according to the Esophagectomy Complications Consensus Group (ECCG) classification. Primary endpoints were the clinical characteristics of chyle leakage (type, severity and treatment). Secondary endpoints were the impact of chyle leakage on duration of thoracic drainage and hospital stay. Chyle leakage was present in 43/314 patients (14%), of whom 24 (56%) were classified as severity A and 19 (44%) as severity B. All patients were successfully treated with either medium chain triglyceride diet (98%) or total parental nutrition (2%). There were no re-interventions for chyle leakage during initial admission, although one patient needed additional pleural drainage during readmission. Patients with chyle leakage had 3 days longer duration of thoracic drainage (bias corrected accelerated (BCa) 95%CI:0.46-0.76) and 3 days longer hospital stay (BCa 95%CI:0.07-0.36), independently of the presence of other complications. Chyle leakage is a relatively frequent complication following esophagectomy. Postoperative chyle leakage was associated with a significant longer duration of thoracic drainage and hospital admission. Nonsurgical treatment was successful in all patients with chyle leakage.

Risk behaviors and STI prevalence among people with HIV in El Salvador.

To date, there are no studies from El Salvador among people with HIV to inform prevention programs. We conducted a study in El Salvador in 2008 among people with HIV using audio computer-assisted interviews on risk behaviors and access to health care. Blood was tested for syphilis and herpes simplex type 2 (HSV-2). Active syphilis was defined as RPR titer ≥1:8. Genital specimens were tested for other sexually transmitted infections (STI) by PCR. We evaluated factors associated with unprotected sex with last stable partner of HIV-negative or unknown status among those reporting a stable partner. A total of 811 HIV-positive individuals participated: 413 men and 398 women. Prevalence of Chlamydia and gonorrhea was low (≤1%), while prevalence of other STI was high: Mycoplasma genitalium (14%), syphilis (15% seropositivity, active syphilis 3%) and HSV-2 (85%). In multivariate analysis, disclosing HIV status to partner (OR 0.2, 95% CI: 0.1-0.3, p<0.001), participation in HIV support groups (OR 0.3, 95% CI: 0.1-0.8, p=0.01), easy access to condoms (OR 0.4, 95% CI: 0.2-0.9, p=0.04) were protective factors for unprotected sex. Reporting a casual partner in the last 12 months (OR 3.6, 95% CI: 1.5-8.5, p=0.004). and having an STI (OR 2.6, 95% CI:1.3-5.5, p=0.02) were associated with an increased odds of unprotected sex. Prevention interventions among HIV-positives in El Salvador should focus on increasing condom access, promoting HIV disclosure and couples testing and reducing the number of partners. The positive role of support groups should be used to enhance behavioral change.

Scorpionism in Central America, with special reference to the case of Panama

Scorpionism in the Americas occurs mainly in Mexico, northern South America and southeast Brazil. This article reviews the local scorpion fauna, available health statistics, and the literature to assess scorpionism in Central America. Notwithstanding its high toxicity in Mexico, most scorpion sting cases in Guatemala, Belize, El Salvador, Nicaragua, and Costa Rica are produced by species in the genus Centruroides that are only mildly toxic to humans despite the existence of ion channel-active toxins in their venoms. Regional morbidity is low with the exception of Panama, where an incidence of 52 cases per 100,000 inhabitants was recorded for 2007, with 28 deaths from 1998 to 2006. Taxa belonging to the genus Tityus (also present in the Atlantic coast of Costa Rica) are responsible for fatalities in Panama, with Tityus pachyurus being the most important species medically. Most Tityus species inhabiting Panama are also found in northern South America from which they probably migrated upon closure of the Panamanian isthmus in the Miocene era. Incorporation of Panama as part of the northern South American endemic area of scorpionism is thereby suggested based on the incidence of these accidents and the geographical distribution of Panamanian Tityus species.(AU)

Prevalence and incidence of multiple sclerosis in Panama (2000-2005).

BACKGROUND: The first cases of multiple sclerosis (MS) in Panama were notified in the 1980s and it was considered a low-risk region for this disease. Between 2000 and 2005, a prevalence study was conducted to characterize MS in Panama. METHODS: An instrument was developed to gather information from clinical files and interviews with previous informed consent. The diagnosis was confirmed by neurologists applying the Poser and McDonald criteria as per the inclusion period. RESULTS: 178 patients from the public and private health sectors were captured between 1970 and 2005. The prevalence rate was 5.24/100,000 inhabitants, and the incidence was between 0.28 and 0.61/100,000 inhabitants. The disease was predominant among women, the mean age +/- SD being 34.76 +/- 10.909 years (1st crisis), and the average number of crises was 2.88. The most common clinical findings were motor, optic neuritis, sensitive and cerebellous. 52.4% presented monosymptomatic manifestations, 71.6% were clinically defined according to Poser's criteria and 55.6% had MS according to McDonald's criteria. 77.8% had their debut with the relapsing-remitting type and presented an Expanded Disability Status Scale score of 2.7 after the first crisis. CONCLUSION: MS is in Panama a neurological pathology with a low prevalence and the results of this investigation improved early treatment and diagnosis of this disease.

Efectos de la malnutricion proteico-calorica materna sobre la concentracion del ARN mensajero de la proteina A del surfactante en pulmones de ratas fetales / Effects of maternal protein-calorie malnutrition on the concentration of protein A messenger RNA in surfactant of fetal rat lungs

The pulmonary surfactant is a lipoproteic complex that serves to lower surface tension at the air-liquid interface in the pulmonary alveoli. Approximately 2 to 4% of the pulmonary surfactant is constituted by the protein A (SP-A). The objective of the study was to determine the effects that maternal protein calorie malnutrition has on the fetal pulmonary growth and the production of SP-A messenger RNA in fetal rats. MATERIALS AND METHODS: Pregnant Sprague Dawley rats were divided into two groups, which received a diet with either 8% or 21% of proteins from gestational day 1 until the day 20. In this last day 11 fetuses were extracted by caesarean section and their lungs were removed to quantify the mRNA of the SP-A. First the mRNA was boosted using the technique of reverse transcriptase and polimerase chain reaction (RT-PCR) and then its concentration was determined by means of fluorodensitometry. RESULTS: There was a reduction in body weight and in wet lung weights of malnourished fetuses in comparison with the normal fetuses (5.03 +/- 0.20 g vs. 4.32 +/- 0.32 g, p < 0.05 and 79.0 +/- 3.8 mg vs. 146.0 +/- 3.4 mg, p < 0.05, respectively). The densitometric analysis of the SP-A mRNA concentration demonstrated a reduction of 32% in the malnourished fetuses (0.52 +/- 0.11 vs. 0.77 +/- 0.07, p < 0.05) compared with the normal fetuses. CONCLUSIONS: The maternal protein calorie malnutrition affected the pulmonary development and the synthesis of the SP-A mRNA. These data suggest that a defect occurrs at pre-transcriptional level that results in a diminution of the concentration of mRNA of SP-A in the neumocytes type II

Intranasal immunization confers protection against murine Pneumocystis carinii lung infection.

To evaluate the feasibility of mucosal immunization against Pneumocystis carinii (Pc) experimental infection, female BALB/c mice were intranasally immunized three times with soluble Pc antigens plus cholera toxin fraction B (Pc-CTB); control groups received either Pc antigen, CTB, or phosphate-buffered saline (PBS) alone. Two weeks after the last immunization, five animals from each group were sacrificed, and cellular and humoral immune responses were evaluated. The remaining five mice were CD4 depleted using a monoclonal antibody against mouse CD4 and inoculated with viable Pc. Significantly higher specific lymphoproliferative responses from tracheobronchial lymph node cells, immunoglobulin M (IgM) and IgG antibody levels in serum, and bronchoalveolar lavage (BAL)-derived IgA antibody concentrations were observed in the Pc-CTB group of mice relative to control groups (P < 0.01). Five weeks after challenge, no Pc organisms were observed in the lung smears of the Pc-CTB group, while the animals receiving antigen, adjuvant, or PBS had progressively higher numbers of Pc microorganisms. By Western blot analysis, a strongly reactive 55- to 60-kDa antigen was recognized by BAL IgA and by serum IgG. In summary, mucosal immunization elicited specific cellular and humoral immune responses and protected against Pc lung infection after immunosuppression.

[Effects of maternal protein-calorie malnutrition on the concentration of protein A messenger RNA in surfactant of fetal rat lungs]. / Efectos de la malnutricion proteico-calorica materna sobre la concentracion del ARN mensajero de la proteina A del surfactante en pulmones de ratas fetales.

UNLABELLED: The pulmonary surfactant is a lipoproteic complex that serves to lower surface tension at the air-liquid interface in the pulmonary alveoli. Approximately 2 to 4% of the pulmonary surfactant is constituted by the protein A (SP-A). The objective of the study was to determine the effects that maternal protein calorie malnutrition has on the fetal pulmonary growth and the production of SP-A messenger RNA in fetal rats. MATERIALS AND METHODS: Pregnant Sprague Dawley rats were divided into two groups, which received a diet with either 8% or 21% of proteins from gestational day 1 until the day 20. In this last day 11 fetuses were extracted by caesarean section and their lungs were removed to quantify the mRNA of the SP-A. First the mRNA was boosted using the technique of reverse transcriptase and polimerase chain reaction (RT-PCR) and then its concentration was determined by means of fluorodensitometry. RESULTS: There was a reduction in body weight and in wet lung weights of malnourished fetuses in comparison with the normal fetuses (5.03 +/- 0.20 g vs. 4.32 +/- 0.32 g, p < 0.05 and 79.0 +/- 3.8 mg vs. 146.0 +/- 3.4 mg, p < 0.05, respectively). The densitometric analysis of the SP-A mRNA concentration demonstrated a reduction of 32% in the malnourished fetuses (0.52 +/- 0.11 vs. 0.77 +/- 0.07, p < 0.05) compared with the normal fetuses. CONCLUSIONS: The maternal protein calorie malnutrition affected the pulmonary development and the synthesis of the SP-A mRNA. These data suggest that a defect occurrs at pre-transcriptional level that results in a diminution of the concentration of mRNA of SP-A in the neumocytes type II.

Antibody to Pneumocystis carinii protects rats and mice from developing pneumonia.

Well-proven mouse and rat models were used to show that polyclonal antisera to Pneumocystis carinii protect against P. carinii pneumonia. Antibodies were obtained from animals that were allowed to recover from severe P. carinii pneumonia after immunosuppression had been stopped and which then were given a booster injection of P. carinii from the same animal species. Mice immunosuppressed with corticosteroids or antibodies to L3T4+ lymphocytes (which are comparable to CD4 cells of humans) and transtracheally inoculated with mouse P. carinii did not develop P. carinii pneumonia if they were passively immunized with antiserum, while mice immunosuppressed and inoculated by identical procedures but not given antibodies developed severe infections. Rats immunosuppressed with corticosteroids and inoculated with rat P. carinii had less severe infections if they were given rat anti-P. carinii antisera. The polyclonal antisera developed in mice provided greater protection for the mice than the polyclonal rat antisera did for the rats; however, the potencies and compositions of the antisera were not quantitated and probably differed. Since both rats and mice can be protected from P. carinii infections with polyclonal antisera, it may be possible to develop vaccines that will elicit protective antibodies in humans.

Immunological markers of disease progression in patients infected with the human immunodeficiency virus.

Identification of inexpensive and technically simple immunological tests useful in predicting the progression to AIDS in human immunodeficiency virus (HIV)-infected patients would be especially welcome in developing countries, in which 80% of HIV-infected patients reside and health budgets are low. In the current study, we evaluated CD4+ and total lymphocyte counts and the concentrations in serum of beta 2-microglobulin, p24 antigen, and immunoglobulin A (IgA) as predictors of disease progression in 74 Panamanian HIV-positive patients and 50 HIV-negative healthy individuals. Total lymphocyte and CD4(+)-cell counts for AIDS patients (1,451 +/- 811 cells/microliters, P < 0.001, and 238 +/- 392 cells/microliters, P < 0.0001, respectively and asymptomatic patients (2,393 +/- 664 cells/microliters, P > 0.05, and 784 +/- 475 cells/microliters, P < 0.001, respectively) were lower than those observed for healthy subjects (2,596 +/- 631 cells/microliters and 1,120 +/- 296 cells/microliters, respectively). The levels of beta 2-microglobulin and IgA in serum were significantly elevated in patients with AIDS (5.7 +/- 3.6mg/liter, P < 0.001, and 541 +/- 265 mg/dl, P < 0.0002, respectively) and asymptomatic infected subjects (3.4 +/- 2.1 mg/liter, P = 0.001, and 436 +/- 216 mg/dl, P < 0.0001, respectively) compared with the levels in healthy subjects (2.2 +/- 0.7 mg/liter and 204 +/- 113 mg/dl, respectively). Nonstatistically significant differences (P > 0.05) for concentrations of p24 antigen between asymptomatic infected patients (29 +/- 13 pg/ml) and AIDS patients (40 +/- 23 pg/ml) were observed. Total lymphocyte counts of 1,750 cells/microliters or less, CD4 counts of 200 cells/microliters or less, beta 2-microglobulin concentrations in serum of 4 mg/liter or higher, concentrations of IgA in serum of 450 mg/dl or higher, and the presence in serum of p24 antigen were correlated with elevated risks for developing AIDS. Monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring the immune status of HIV-positive patients.

An oligonucleotide probe derived from kDNA minirepeats is specific for Leishmania (Viannia).

Sequence analysis of Leishmania (Viannia) kDNA minicircles and analysis of multiple sequence alignments of the conserved region (minirepeats) of five distinct minicircles from L. (V.) braziliensis species with corresponding sequences derived from other dermotropic leishmanias indicated the presence of a sub-genus specific sequence. An oligonucleotide bearing this sequence was designed and used as a molecular probe, being able to recognize solely the sub-genus Viannia species in hybridization experiments. A dendrogram reflecting the homologies among the minirepeat sequences was constructed. Sequence clustering was obtained corresponding to the traditional classification based on similarity of biochemical, biological and parasitological characteristics of these Leishmania species, distinguishing the Old World dermotropic leishmanias, the New World dermotropic leishmanias of the sub-genus Leishmania and of the sub-genus Viannia.

Optimización de la técnica de inmunoelectrotransferencia (western blot) para la confirmación de la infección por el virus de immunodeficiencia humana (VIH) en Panamá / Optimization of the immunoelectrophoresis technic (western blot) for the confirmation of human immunodeficiency virus infection (HIV) in Panama

The purpose of this study is to report the results of the authors' investigation to apply the western blot technique (WB UP-LCS) in the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection. To do this, the authors separated the proteins of the HIV-1 virus by electrophoresis, based on their molecular weight, in poliacilamide gel with SDS (SDS-PAGE) during 3 hours at 200 volts. Then they electrotransferred these proteins to nitrocellulose paper during four hours at 200 milliamperes, with the aid of external cooling. The nitrocellulose strips were evaluated considering the incubation time (1 and 16 hours), two conjugates (human anti IgG with Peroxidase and human anti IgG Biotin plus Streptatividine with Peroxidase) and two dilutions of the patients' sera (1/50 and 1/100). Based on their results the Authors conclude that, in the first place, the optimal conditions for the test include a dilution of 1/100 of the patients serum, incubation of the serum for 16 hours and the use of the conjugate of anti human IgG with Biotin and Streptavidine with Peroxidase; secondary, that the immunologic reactivity against proteins p24 and gp 160/120 is the most important diagnostic criterion for the confirmation of infection with HIV-1 and that they obtained a diagnostic correlation of 100% at a cost which was 5 to 7 times less than that of the commercial system

[Optimization of the immunoelectrophoresis technic (western blot) for the confirmation of human immunodeficiency virus infection (HIV) in Panama]. / Optimización de la técnica de inmunoelectrotransferencia (western blot) para la confirmación de la infección por el virus de immunodeficiencia humana (VIH) en Panamá.

The purpose of this study is to report the results of the authors' investigation to apply the western blot technique (WB UP-LCS) in the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection. To do this, the authors separated the proteins of the HIV-1 virus by electrophoresis, based on their molecular weight, in poliacilamide gel with SDS (SDS-PAGE) during 3 hours at 200 volts. Then they electrotransferred these proteins to nitrocellulose paper during four hours at 200 milliamperes, with the aid of external cooling. The nitrocellulose strips were evaluated considering the incubation time (1 and 16 hours), two conjugates (human anti IgG with Peroxidase and human anti IgG Biotin plus Streptatividine with Peroxidase) and two dilutions of the patients' sera (1/50 and 1/100). Based on their results the Authors conclude that, in the first place, the optimal conditions for the test include a dilution of 1/100 of the patients serum, incubation of the serum for 16 hours and the use of the conjugate of anti human IgG with Biotin and Streptavidine with Peroxidase; secondary, that the immunologic reactivity against proteins p24 and gp 160/120 is the most important diagnostic criterion for the confirmation of infection with HIV-1 and that they obtained a diagnostic correlation of 100% at a cost which was 5 to 7 times less than that of the commercial system.

[Cloning of kDNA minicircles in different species of Leishmania and its use as probes for diagnosis]. / Clonaje de minicírculos de kADN en diferentes especies de Leishmania y su uso como sondas para diagnóstico.

The present study describes the cloning procedure for fragments of kinetoplast DNA minicircles from different Leishmania species and its use for detecting the presence of these parasites. Our methodology was as follow: the DNA of the kinetoplast from Leishmania mexicana amazonensis and Leishmania braziliensis panamensis was extracted, purified and digested with the enzyme Dra I. These fragments were cloned in the site for Hinc II in the plasmid pKS. E. coli was the bacterial strain used for transforming and amplifying the cloned fragments; the selection was carried out in LB medium supplemented with ampicillin. With the clones suspected to be positives we run a Southern blot and total kDNA, from each Leishmania species, was used as hybridization probe. Finally, the cloned purified fragments were tested as diagnostic probes against kDNA from eleven different species of Leishmania and one of Trypanosoma cruzi parasites. After cloning, transforming, amplifying and selecting, we obtained two probes of fragments of kDNA minicircles: one from L. m. amazonensis and the other from L. b. panamensis. Both probes showed high sensitivity for diagnosing cutaneous Leishmania complexes (Mexicana or Braziliensis); however, we observed a low grade crossreaction between some species belonging to the same complex. It is necessary to continue studies in order to obtain subfragments of these probes with a higher grade of specificity at the level of species and subspecies.

[Determination of soluble interleukin-2 receptor in patients with American Trypanosomiasis in Panama]. / Evaluación del receptor soluble de interleucina--2 en pacientes con Tripanosomiasis Americana en Panamá.

The quantitative determination of Inter leukin-2 Receptor (sIL-2R) in the serum of patients with acute or chronic Chagas disease is compared with values found in normal individuals. The mean value of soluble IL-2R in patients with acute Chagas' disease was found to be 3,282 +/- 171 U/ml. The mean value of sIL-2R in serum samples from chronic chagasic patients was 511 +/- 207 U/ml, while in the control or "normal" group of persons the mean value for sIL-2R was 366 +/- 108 U/ml. In patients with early or acute infections with T. cruzi, the serum levels of sIL-2R was usually above 1000 U/ml. However, the correlation with anti-T. cruzi antibodies and levels of sIL-2R was not always directly proportional. Specific antibodies anti-T. cruzi in serum from chronic chagasic patients, shown at low or high levels, did not reveal a proportional correlation with serum levels of sIL-2R which tend to be significantly lower than in early or acute infections. It is considered that high values for sIL-2R are related with the parasite activity and its pathologic interaction with the host. It is possible that high levels of sIL-2R could serve as an indicator of early or acute Chagas' disease and be useful in assessment of disease conditions and response to therapy.