Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

Low tumor interleukin-1ß expression predicts a limited effect of adjuvant platinum-based chemotherapy for patients with completely resected lung adenocarcinoma: An identification and validation study.

INTRODUCTION AND OBJECTIVES: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy. MATERIALS AND METHODS: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS. The results were validated in an independent validation cohort (n = 93). RESULTS: Fifty-two of 97 (54 %) patients in the discovery cohort and 50 of 93 (54 %) in the validation cohort received adjuvant chemotherapy; forty-four (85 %) patients in the discovery cohort and 37 (74 %) in the validation cohort received four cycles as planned. In patients with low IL-1ß-expressing tumors, RFS and OS were worse after adjuvant chemotherapy than after observation. The limited effect of adjuvant chemotherapy for patients with low IL-1ß-expressing tumors was confirmed in the validation cohort. Additionally, RFS and OS were prolonged by adjuvant chemotherapy only in patients with high IL-1ß-expressing tumors in the validation cohort. CONCLUSIONS: This study identified and validated low tumor IL-1ß expression as a potential biomarker of a limited response to adjuvant platinum-based chemotherapy after complete resection of pulmonary adenocarcinoma. This finding has the potential to inform adjuvant treatment decisions.

Evaluation of a Specific Modulation Frequency Technique for Detecting H. pylori in a Model of Experimentally Infected Mice.

Diagnosis of Helicobacter pylori is challenging. Diverse techniques have been developed for accurate diagnosis. However, they have some limitations. This research investigated the efficacy of specific modulation frequency (SMF) compared to other routine diagnostic methods for detecting H. pylori in gastric biopsy samples of experimentally infected mice. One-hundred and fifty healthy male C57BL/6 mice were included and divided into the control and treatment groups. The mice in the treatment group were treated with 0.2 ml of 0.2 M NaHCO3 to neutralize gastric acidity. Then, 109 colony-forming units of H. pylori (ATCC 43504) mixed in PBS were used intragastrically to inoculate the mice. Mice were kept for up to 28 days and examined on days 0, 7, 14, 21, and 28 using culture, polymerase chain reaction (PCR), and SMF. On day 0, only the SMF and PCR could detect the H. pylori in the stomach of 60% and 20% of mice, respectively. On day 7, culture, PCR, and SMF could detect H. pylori in 40%, 80%, and 100% of mice, respectively. SMF detected all infected mice from days 7 to 28 (100%). PCR detected all H. pylori-infected mice at days 14 to 27 (100%). Another test (culture) detected all infected mice only on day 28. Significant differences were found among the three diagnostic methods on days 0, 7, 14, and 21 of the experiment (P<0.05). SMF was found to have high sensitivity and specificity for H. pylori detection in the early stages of infection.

Surgical margin clearance and extended chemotherapy defines survival for synchronous oligometastatic liver lesions of the ductal adenocarcinoma of the pancreas.

BACKGROUND: The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. METHODS: Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. RESULTS: Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. CONCLUSION: This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival.

BACKGROUND: Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD: Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS: The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION: Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.

Site of relapse of ductal adenocarcinoma of the pancreas affects survival after multimodal therapy.

BACKGROUND: Ductal adenocarcinoma of the pancreas (PDAC) remains one of the most lethal malignancies. To date, no guidelines exists for isolated resectable metachronous disease. It is still unknown, which patients may benefit from relapse surgery. The aim of our study was to compare disease free survival (DFS) and post relapse survival (PRS) in patients with isolated local recurrence, metachronous hepatic or pulmonary metastases. METHODS: Patients with isolated resectable local recurrence, metachronous hepatic or pulmonary metastases were included for survival analyses. PRS of surgically treated patients (local (n = 11), hepatic (n = 6) and pulmonary metastases (n = 9)) was compared to conservatively treated patients (local (n = 17), hepatic (n = 37) and pulmonary metastases (n = 8)). RESULTS: Resected PDAC patients suffering from isolated metachronous hepatic metastases initially had a higher T-stage and venous invasion (V1) compared to the other patients. DFS in the metachronous pulmonary metastases group was longer compared to DFS of the hepatic metastases and local recurrence groups. Surgical resection significantly improved PRS in patients with local recurrence and pulmonary metastases, when compared to patients receiving chemotherapy alone. Very-long term survivors (> 5 years) were detected following secondary resection of local recurrence and 45% of these patients were still alive at the end of our study period. CONCLUSION: Although DFS in PDAC patients suffering from isolated local recurrence was dismal and comparable to that of patients with isolated hepatic metastases, very-long term survivors were present only in this group. These results indicate that a surgical approach for isolated local recurrence, if anatomically possible, should be considered.

Citrate and celecoxib induce apoptosis and decrease necrosis in synergistic manner in canine mammary tumor cells.

Celecoxib and citrate have been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activities of these agents in canine mammary tumors have not been well demonstrated. The aim of our study was to investigate the apoptotic and antiproliferative effects of citrate and celecoxib, individually and in combination, on canine mammary tumor cell line CF41­Mg. MTT assay was performed to determine cell viability, and Annexin­PI test was performed to evaluate apoptosis induction. MTT assay results revealed that compared with the control groups, treatment groups, as both single and combined treatments, showed significant inhibition of tumor growth in a dose­dependent manner. IC50 concentrations of citrate and celecoxib were defined 26mM and 22µM, respectively. In another set of experiment, significant increase in cell apoptosis was observed at IC50 concentrations of citrate and celecoxib after 48h incubation. In spite of that, simultaneous treatment of cells with citrate and celecoxib eventuated with meaningful toxicity augmentation and induction of apoptosis at lower concentrations. Also necrotic cells were decreased by coadministration of the two agents. In conclusion, the present study indicates significant cytotoxic and apoptotic effects of citrate and celecoxib coadministration on CF41­Mg cells, and proposes new strategies for counteracting cancer cells proliferation and overcoming chemo resistance.

Serum inflammatory factors and circulating immunosuppressive cells are predictive markers for efficacy of radiofrequency ablation in non-small-cell lung cancer.

In recent years, percutaneous radiofrequency ablation (RFA) has been developed as a new tool in the treatment of non-small-cell lung cancer (NSCLC) in non-surgical patients. There is growing evidence that RFA-mediated necrosis can modulate host immune responses. Here we analysed serum inflammatory factors as well as immunosuppressive cells in the peripheral blood to discover possible prognostic indicators. Peripheral blood and serum samples were collected before RFA and within 3 months after the treatment in a total of 12 patients. Inflammatory cytokines and growth factors were measured in serum by the Bio-Plex assay. Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs ) were evaluated in the peripheral blood via flow cytometry. In patients developing local or lymphogenic tumour relapse (n=4), we found an early significant increase in the concentration of tumour necrosis factor (TNF)-α as well as chemokine (C-C motif) ligand (CCL)-2 and CCL-4 compared to patients without relapse (n=4) and healthy donors (n=5). These changes were associated with an elevated activity of circulating MDSC indicated by an increased nitric oxide (NO) production in these cells. Elevated serum levels of TNF-α, CCL-2 and CCL-4 associated with an increased NO production in circulating MDSCs might be an early indicator of the incomplete RFA and subsequently a potential tumour relapse in NSCLC.

Simultaneous computed tomography-guided biopsy and radiofrequency ablation of solitary pulmonary malignancy in high-risk patients.

BACKGROUND: In recent years experience has been accumulated in percutaneous radiofrequency ablation (RFA) of lung malignancies in nonsurgical patients. OBJECTIVES: In this study, we retrospectively evaluated a simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions. METHODS: CT-guided transthoracic core needle biopsy of solitary pulmonary lesions suspicious for malignancy was performed and histology was proven based on immediate frozen sections. RFA probes were placed into the pulmonary tumors under CT guidance and the ablation was performed subsequently. The procedure-related morbidity was analyzed. Follow-up included a CT scan and pulmonary function parameters. RESULTS: A total of 33 CT-guided biopsies and subsequent RFA within a single procedure were performed. Morbidity of CT-guided biopsy included pulmonary hemorrhage (24%) and a mild pneumothorax (12%) without need for further interventions. The RFA procedure was not aggravated by the previous biopsy. The rate of pneumothorax requiring chest tube following RFA was 21%. Local tumor control was achieved in 77% with a median follow-up of 12 months. The morbidity of the CT-guided biopsy had no statistical impact on the local recurrence rate. CONCLUSIONS: The simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions is a safe procedure. The potential of this combined approach is to avoid unnecessary therapies and to perform adequate therapies based on histology. Taking the local control rate into account, this approach should only be performed in those patients who are unable to undergo or who refuse surgery.

Presence of atrazine in the biological samples of cattle and its consequence adversity in human health.

BACKGROUND: Cattle can be considered as an important source for herbicides through nutrition. Therefore, herbicide residue in animal products is a potential human exposure to herbicides causing public health problems in human life. Triazines are a group of herbicides primarily used to control broadleaf weeds in corn and other feed ingredients and are considered as possible human carcinogens. To evaluate trace residue of these pollutants molecular imprinted solid phase extraction (MISPE) method has been developed, using biological samples. METHODS: Blood samples were taken from the jugular vein of 45 Holstein cows in 3 commercial dairy farms in Khuzestan Province, Iran. Urine samples were also taken from the cows. RESULTS: The mean ± SD concentrations of atrazine in serum and urine samples of the study group (0.739 ± 0.567 ppm and 1.389 ± 0.633 ppm, respectively) were higher (P < 0.05) than the concentrations in serum and urine samples of the control group (0.002 ± 0.005 ppm and 0.012 ± 0.026 ppm, respectively). CONCLUSION: Atrazine in the feed ingredients ingested by cattle could be transferred into the biological samples and consequently can be considered as a potential hazard for the public health.

[Pseudosarcoidotic ganglionic mediastinal tuberculosis]. / Une forme pseudosarcoïdosique de la tuberculose ganglionnaire médiastinale.

INTRODUCTION: The aetiological inquiry in the presence of systemic granulomatosis should consider some uncommon forms of tuberculosis infections. For instance, Poncet's tuberculous rheumatism is a rare entity subject to controversy. CASE REPORT: A 32-year-old man presenting febrile polyarthritis associated with spontaneously vanishing erythematous papular skin rash. The tests revealed a biological inflammatory syndrome and mediastinal lymph nodes. The biopsies showed cutaneous and mediastinal adenoid granulomatosis. The cutaneous lesions resolved spontaneously. The culture of the ganglionic sample was positive. The evolution was favourable under treatment and the articular pain disappeared within a few days. CONCLUSION: Poncet's tuberculous rheumatism may underly evolving visceral tuberculosis. It's presence requires a search for tuberculosis when systemic granulomatosis with cutaneous and articular involvement may simulate sarcoidosis.

Garlic (Allium sativum L.) as a potential antidote for cadmium and lead intoxication: cadmium and lead distribution and analysis in different mice organs.

Analysis and distribution of Pb and Cd in different mice organs including liver, kidney, spleen, heart and blood were evaluated after treatment with different aqueous concentrations of garlic (12.5-100 mg/l). Atomic absorption spectrometry (AAS) was used for analysis of Pb and Cd in these organs. Treatment of Cd-Pb exposed mice with garlic (12.5-100 mg/l) reduced Pb concentrations by 44.65, 42.61, 38.4, 47.56, and 66.62% in liver, kidney, heart, spleen and blood respectively. Moreover, garlic reduced Cd levels by 72.5, 87.7, 92.6, 95.6, and 71.7% in liver, kidney, heart, spleen and blood respectively. The suppressed immune responses in mice pretreated with Cd-Pb mixture were reversed by 48.85, 55.82, 81.4 and 90.7 in the presence of 100, 50, 25, and 12.5 mg/ml of garlic extract.

[Primary non-Hodgkin's lymphoma of the adrenals. A case report]. / Lymphome malin non hodgkinien primitif de la surrénale. A propos d'un cas.

Bilateral primary non-Hodgkin's lymphoma (NHL) of the adrenals is uncommon. Less than 70 cases have been described in the literature. The symptoms of disease are variable and depend on the tumor size and the presence of adrenal insufficiency . We report a case of large diffuse B-cell adrenal lymphoma discovered in a 40-year-old woman presenting bilateral lumbar pain. Hormonal exploration demonstrated adrenal insufficiency. Imaging explorations showed a large and bilateral adrenal mass. Percutaneous CT-guided biopsy of the adrenal and search for extension revealed primary bilateral adrenal lymphoma. After glucocorticoid substitution, treatment was based on a CHOP regimen chemotherapy; outcome was unfavourable after the second cure; the patient died from septic shock. The diagnosis of primary adrenal non-Hodgkin lymphoma should be investigated in patients with a rapidly growing bilateral adrenal mass associated with adrenal insufficiency.

[A case of myopathy associated with hypothyroidism and hyperprolactinaemia]. / Un cas de myopathie révélant une hypothyroïdie périphérique avec syndrome tumoral hypophysaire.

UNLABELLED: We report a case of a serious myopathy related to hypothyroidism with pituitary enlargement and hyperprolactinemia. CASE REPORT: Mr D.L 33 years old man suffering from myalgia, muscular weakness and cramps for six months. The laboratory check-up revealed a high serum creatin phosphokinase level, an autoimmune hypothyroidism, hyperprolactinemia and pituitary enlargement. The electromyogram was normal and the muscle biopsy showed no obvious inflammation. The outcome was favourable under L. thyroxin. DISCUSSION: The frequency of myopathy during hypothyroidism ranges from 30 to 80%. The main symptoms related are weakness, muscular cramps and myalgia. However, hyperprolactinemia and pituitary enlargement described in this case are due to reactional mechanism. These several hypothyroid manifestations improve remarkably under L.thyroxin. CONCLUSION: Proximal myopathy may rarely be displayed as the sole manifestation of hypothyroidism. Therefore, it is recommended that hypothyroid myopathy should be taken into account during differential diagnosis of proximal muscle weakness.

[Orbital involvement in IgD Kappa myeloma]. / Atteinte de l'orbite au cours d'un myélome à IgD Kappa.

INTRODUCTION: IgDkappa myeloma accounts for less than 2% of all myeloma cases. Orbital involvement is uncommon in myeloma and the authors suggest a possible predilection for IgD myeloma to involve the orbit. CASE REPORT: A 67-year-old women was admitted for diffuse bone pain and painful ptosis of the right eye. The symptoms had progressed over approximately 1 year and were associated with a severe decline in general health. The biochemical, hematological, and radiological investigations suggested the diagnosis of an IgD kappa myeloma. Orbital x-ray showed destruction of the greater and lesser right wing of the sphenoid bone. Treatment was polychemotherapy. The course of the disease was very rapid and death occurred within 17 months from renal failure and amyloidosis. DISCUSSION: Orbital involvement by myeloma occurs in 0.3% of cases and the majority are unilateral. The typical orbital symptoms include ptosis, diplopia, loss of vision, and pain. This was not considered to contribute to poor prognosis but may affect the functional prognosis.

Coeliac disease in Sudanese children with clinical features suggestive of the disease.

Our prospective hospital-based study examined frequency, clinical presentation and serological indicators of coeliac disease that correlated with intestinal biopsy among high-risk Sudanese children. From July 2001 to July 2002, 80 children aged 15 months-18 years presented with poor appetite, weight loss, pallor and proximal muscle wasting. We diagnosed coeliac disease in 18 (22.5%). Antigliadin antibodies (AGA-IgG, AGA-IgA or both) were high in 44; endomysial antibody retest was high in 30. Guardians of 12 children refused consent for biopsy. The other 18 were biopsied: 5 had total villous atrophy, 8 subtotal and 5 partial. All improved with gluten-free diet. Degree of villous atrophy did not correlate with diarrhoea duration or severity, anaemia severity or serological titres.

[Severe primary hyperparathyroidism and vitamin D deficiency]. / Hyperparathyroïdie primitive sévère et déficit en vitamine D.

Primary hyperparathyrodism is a common disease, often asymptomatic. A young post-partum woman was hospitalized for functional impotence of the upper right limb and poor health status. Laboratory tests revealed severe primary hyperparathyroidism (osteitis fibrosa cystica and nephrolithiasis) associated with vitamin D deficiency. Technetium 99m and thallium parathyroid scintigraphy showed increased uptake under the left thyroid lobe. After surgical resection of a parathyroid adenoma, serum calcium fell markedly and parathyroid levels declined but remained above normal. Calcium and 25(OH)-vitamin D supplementation led to normal calcium and vitamin D levels in three Months, with marked improvement in the bone lesions visualized on the six-Month x-rays. Based on this observation, we describe the many radiological aspects of bone involvement in long-standing hyperparathyroidism aggravated by vitamin D deficiency. Early diagnosis of hyperparathyroidism is crucial.

Typing of urinary JC virus DNA offers a novel means of tracing human migrations.

Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as a usually harmless symbiote among human beings. JCV propagates in the adult kidney and excretes its progeny in urine, from which JCV DNA can readily be recovered. The main mode of transmission of JCV is from parents to children through long cohabitation. In this study, we collected a substantial number of urine samples from native inhabitants of 34 countries in Europe, Africa, and Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its DNA sequence was determined. A worldwide phylogenetic tree subsequently constructed revealed the presence of nine subtypes including minor ones. Five subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that overlapped with each other at their boundaries. The entire Europe, northern Africa, and western Asia were the domain of EU, whereas the domain of Af2 included nearly all of Africa and southwestern Asia all the way to the northeastern edge of India. Partially overlapping domains in Asia were occupied by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV subtypes in a pocket or pockets that were separated by great geographic distances from the main domains of those subtypes. Certain of these pockets can readily be explained by recent migrations of human populations carrying these subtypes. Overall, it appears that JCV genotyping promises to reveal previously unknown human migration routes: ancient as well as recent.

In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma.

The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.