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Anil Potti

Publications and source records attributed to Anil Potti.

72 records · Page 4Linked to original sources
PubMed2002

Late adrenal metastasis in operable non-small-cell lung carcinoma.

Treatment of early-stage (I, II, and some IIIA) non-small-cell lung cancer (NSCLC) is curative resection. Simultaneous isolated adrenal metastasis represents a dilemma. Although many studies addressing the management of adrenal metastasis diagnosed simultaneously with NSCLC have been published, only very few reports of late adrenal metastasis can be found in the literature. Our purpose is to discuss the management of solitary late (metachronous) adrenal metastasis from operable NSCLC based on published experience. We describe a patient with a solitary metachronous adrenal metastasis diagnosed 3 years after resection of NSCLC. Adrenalectomy was done, followed by combination chemotherapy with paclitaxel and carboplatin. MEDLINE literature on similar cases was reviewed and updated. Only 18 cases have been reported from 1965 to 2000. The median interval between the diagnosis of NSCLC and development of adrenal metastasis was 11.5 months. All patients were male. Unilateral adrenal metastases were reported in 15 patients, whereas 3 had bilateral metastases. Five patients were treated with adrenalectomy, and eight patients were treated with adrenalectomy and postoperative adjunctive chemotherapy. Chemotherapy alone was used in two patients and two patients underwent palliative radiation therapy. One patient was treated with intraarterial chemotherapy followed by radiation therapy. Solitary metachronous adrenal metastases are rare. There are no standard treatment guidelines for this group of patients. Review of the literature showed that median survival after treatment was 19 months for the group treated with adrenalectomy followed by chemotherapy; 15 months for the chemotherapy group; 14 months for the adrenalectomy group; and 8 months for the group treated with palliative radiation.

Adrenal Gland Neoplasms↗
PubMed2002

Role of Helicobacter pylori infection in the incidence and clinical course of monoclonal gammopathy of undetermined significance.

OBJECTIVES: We aimed to evaluate the hypothesis that chronic antigenic stimulation is an etiological factor of monoclonal gammopathy of undetermined significance (MGUS) with special relevance to Helicobacter pylori infection. METHODS: We performed a retrospective, observational study. The diagnosis of MGUS was based on serum protein electrophoresis, serum IgM levels (<3 gr/dl), urinary M protein, a normal bone marrow biopsy, normal renal function, and a negative skeletal survey. H. pylori infection was ascertained by rapid urease testing and endoscopy with gastric biopsy for histology. Eradication of H. pylori was assessed by urea breath test and stool antigen assay 4 wk after completion of an appropriate treatment regimen. RESULTS: Sixty-nine patients with MGUS were included in the study. Of these, 57 had undergone evaluation for H. pylori infection for various GI symptoms. Thirty-nine of 57 patients (68.42%) with MGUS also had evidence of H. pylori infection. In 11 of these 39 patients (28.21%), eradication of H. pylori infection with an appropriate regimen led to normalization of the serum protein electrophoresis and resolution of the gammopathy. CONCLUSION: The results of our study give increased credibility to the theory that in a proportion of patients the pathogenesis of MGUS involves chronic antigenic stimulation and H. pylori is implicated. The search for H. pylori infection and an attempt to eradicate the bacterium in positive cases seem to be appropriate in patients diagnosed with MGUS.

Aged↗
PubMed2002

Predictive value of clinical features at initial presentation in pancreatic adenocarcinoma: a series of 308 cases.

Pancreatic cancer is the fourth leading cause of cancer death in both men and women with a mortality incidence ratio of 0.99. In an effort to describe the role of clinical features at initial presentation, we conducted a retrospective observational study in patients with a biopsy-proven diagnosis of adenocarcinoma of the pancreas. Between 1986 and 2001, 308 patients (160 males, 148 females) were diagnosed with pancreatic adenocarcinoma. The mean age at diagnosis was 70.1 yr (range: 34-96 yr). The mean survival was 7.6 mo (range: 0-97 mo). Statistical analysis was performed using log-rank tests and analysis of variance. As expected, age at diagnosis was a significant factor affecting survival, with older patients doing relatively poorly (p < 0.05). Patients with a good performance status performed significantly better than those with a poor performance status (p < 0.01). In addition, the presence of the tumor in the head of the pancreas was a predictor for improved survival (p < 0.01). Although smoking increased the chances of detection at an earlier age, neither diabetes mellitus nor a positive smoking history had a statistically significant effect on the survival. Pancreatic adenocarcinoma is a disease of the elderly associated with a poorer outcome. Knowledge of possible clinical predictors of survival may lead to better patient counseling regarding prognosis.

Adenocarcinoma↗
PubMed2002

Pancreatic metastasis and extrahepatic biliary obstruction in squamous cell lung carcinoma.

Primary lung cancer frequently metastasizes to distant organs. The pancreas is a relatively infrequent site of metastasis. As a result, extrahepatic bile duct obstruction (EHBDO) resulting from pancreatic metastasis from lung cancer is extremely rare and occurs mostly with small-cell lung cancer (SCLC). We report an unusual case in which a patient presented with jaundice and, after extensive workup, was diagnosed with squamous cell carcinoma of the lung with metastasis to the pancreas causing EHBDO. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and the obstruction was relieved with a stent placement. The patient was treated with combination chemotherapy (carboplatin and paclitaxel) with a good clinical and radiographic response.

Carcinoma, Squamous Cell↗
PubMed2002

Spinal epidural abscess after corticosteroid injections.

Although spinal epidural abscess is uncommon, its incidence is likely to rise with increasing use of epidural injections for the control of lower back pain. We report a case of spinal epidural abscess after epidural steroid injection. The abscess resolved with conservative medical management.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels in acute myocardial infarction.

The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome.

Adult↗
PubMedDate not supplied

Effect of low-molecular-weight heparin on potassium homeostasis.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are being preferred to unfractionated heparin (UFH) because of their superior convenience and a comparable or slightly better toxicity profile. Whether LMWH has an inhibitory effect on aldosterone that causes hyperkalemia is yet uncertain. METHODS: Twenty-eight patients (all male; mean age: 70 years, range 52-87 years) placed on LMWH therapy (40 mg subcutaneously every 12 h) for deep venous thrombosis prophylaxis after an operation were included in the study. Transtubular potassium concentration gradient (TTKG) was calculated 1 day prior to LMWH therapy and again after 4 days of treatment. Of the 28 patients enrolled in the study, we were able to calculate the TTKG in only 19 patients: 9 had a urinary osmolarity (either before or after LMWH therapy) less than the serum osmolarity, making the TTKG calculation unreliable. The Wilcoxon signed-rank test was used to analyze differences in the median serum potassium levels and TTKG before and after LMWH therapy. RESULTS: All patients had adequate renal function (creatinine clearance >90 ml/min). Mean (+/- SD) serum potassium concentration before LMWH was 4.25 (+/- 0.40) mmol/dl. It increased to 4.35 (+/- 0.41) mmol/dl after initiating LMWH therapy (p = 0.09). Similarly, the mean (+/- SD) TKKG calculated was 5.52 (+/- 2.33) before and 5.97 (+/- 3.06) after 4 days of LMWH (p = 0.54). CONCLUSIONS: Unlike UFH, LMWH (Lovenox in doses used for postoperative prophylaxis against deep venous thrombosis does not seem to have a significant effect on potassium homeostasis.

Aged↗
PubMedDate not supplied

Role of immunohistochemical identification of Her-2/neu and detection of variability in overexpression in pancreatic carcinoma.

INTRODUCTION: Her-2/neu overexpression has been recently shown to be a poor prognostic factor in breast carcinoma. Overexpression has also been demonstrated in adenocarcinoma of the pancreas but the significance is unclear. We attempted to study the role of Her-2/neu overexpression, detected by immunohistochemistry, in pancreatic carcinoma and also examined for variability of overexpression across different tissue sections on individual tumor specimen. MATERIALS AND METHODS: Records of all patients with adenocarcinoma of the pancreas, diagnosed and followed between 1986 and 2001 at a tertiary care oncology center were reviewed. Archival pathological samples were analyzed for Her-2/neu expression using the Hercep immunohistochemical assay (DAKO). A score of 2+ or greater on the assay was considered positive for Her-2/neu expression. When tumors were found to be Her-2/neu-positive, they were assessed for variability of expression of Her-2/neu by staining different sections of individual tumor blocks. Log-rank tests and Cox proportional hazards methods were used to analyze survival data. RESULTS: Three hundred and eight patients were included in our study. The mean age was 70 years. Forty-eight out of 308 specimens (16%) were positive for Her-2/neu expression. The mean survival in the Her-2/neu-positive group was 11 months and in the Her-2/neu-negative group was 7 months (p=.03). Of the 48 patients with Her-2/neu-positive tumors, 16 showed variable overexpression (33%). Multivariate analysis did not reveal statistical difference in survival between the uniformly expressing and variably expressing tumors. CONCLUSION: Her-2/neu overexpression detected by immunohistochemistry does not appear to be a poor prognostic factor in patients with adenocarcinoma of the pancreas. Also, there is significant variability in the level of Her-2/neu expression across tumor sections in individual patients, which can potentially lead to considerable misclassification. Hence, we believe that, pending further studies, Her-2/neu may not be an appropriate target for therapy in pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Identification and relationship of HER-2/neu overexpression to short-term mortality in primary malignant brain tumors.

INTRODUCTION: HER-2/neu overexpression has been associated with poor prognosis in solid tumors. The extent to which HER-2/neu is overexpressed in human central nervous system malignancies is unclear. We retrospectively analyzed a large cohort of patients with primary brain tumors to evaluate the prognostic role of HER-2/neu overexpression and clinical characteristics at presentation in patients with shortened survival (< 6 months). MATERIALS AND METHODS: Between 1986 and 2001, 136 patients (81 males, 55 females) with a mean age of 69 years (age range: 49-78 years), with a biopsy-proven diagnosis of a primary malignant brain tumor and survival of < six months from the time of diagnosis, were identified. Archival tissue samples were analyzed for HER-2/neu overexpression using the Hercep immunohistochemical assay. A score of 2+ or greater on the assay was considered positive for HER-2/neu overexpression. Short-term mortality (less than 6 months) and its predictors were evaluated using multiple logistic regression. RESULTS: Mean overall survival was 2.8 months. HER-2/neu overexpression was detected in 23 out of 136 specimens (17%). However, HER-2/neu overexpression did not predict increased 6-month mortality (p = 0.43). Interestingly, the presence of HER-2/neu overexpression was associated with a significantly increased risk of an associated second primary malignancy in addition to the primary brain tumor. Other factors examined did not predict increased 6-month mortality either, including site of tumor (p = 0.54), tumor histology (p = 0.77) and presenting symptoms (p = 0.32). CONCLUSION: Her-2/neu overexpression was detected in 17% of patients with primary brain tumors, but, did not predict increased short-term mortality in patients with brain tumors surviving less than six months. We were not able to identify any clinical variables that could predict survival in our patient population. At present, there are few reliable prognostic indicators for brain tumors. Further studies are needed to specify whether certain tumor subtypes are more likely to overexpress HER-2/neu and to evaluate the role of HER-2/neu as a target for therapy in malignant brain tumors.

Adult↗
PubMedDate not supplied

An epidemiological study evaluating the relationship of distance from a tertiary care cancer center to early detection of colorectal carcinoma.

OBJECTIVE: AJCC stage at diagnosis determines the treatment approach and indirectly predicts outcome in patients with colorectal carcinoma. The purpose of our study was to investigate whether there was a delay in diagnosis leading to a more advanced stage at diagnosis (which affects outcome) of patients with colorectal cancers because of distance from a referral center, after positive fecal occult blood testing (FOBT). DESIGN: Our retrospective observational study involved all cases of colonic and rectosigmoid cancers that were referred for an endoscopic procedure after an initial positive FOBT done as a part of routine screening in asymptomatic patients. PARTICIPANTS: Roger Maris Cancer Center and University of North Dakota School of Medicine and Health Sciences. RESULTS: Between the years 1996-2001, 178 subjects with biopsy-proven colon cancer and 80 patients with rectosigmoid cancer were included in our study. Pearson's correlation coefficients were constructed to look at the relationship between distance from a referral center (place where the diagnosis was made) and stage at diagnosis in patients with colonic and rectosigmoid malignancies. For the colon cancer group, the regression coefficient between AJCC stage at diagnosis and distance from the referral center was 0.013 and for rectosigmoid cancers it was 0.12. Even after stratifying distances into tertiles, the correlation coefficients did not show a significant relationship (0.04 for colon and 0.16 for rectosigmoid cancers). CONCLUSION: Distance (of residence) from a tertiary care center does not seem to be a barrier to early diagnosis of colorectal carcinoma and primary care providers in rural settings are referring patients appropriately leading to optimal outcomes.

Aged↗
PubMedDate not supplied

Immunohistochemical detection of C-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a low-grade lymphoproliferative malignancy that is extremely refractory to chemotherapy. Commonly used treatments have yielded unfavorable response rates (30% complete remission). We evaluated the incidence of c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in patients with MCL in an effort to identify possible targets for therapeutic intervention. MATERIALS AND METHODS: Patients with a diagnosis of MCL based on CD5 positivity associated with cyclin D1 positivity and CD23 negativity on the lymph node/bone marrow specimen were included in our retrospective study. CD117 overexpression was performed using immunohistochemistry on archival specimens. VEGF expression was detected by the avidin-biotin-complex method. RESULTS: Between 1997 and 2001, we identified 17 patients with MCL (9 males, 8 females) with a mean age of 57 years (age range: 42-66 years). The mean overall survival was 34 months (range: 11-60 months). VEGF expression was identified in 7 out of 17 (41.18%) patients with MCL. Among the VEGF-positive patients (n = 7, 41.1%), the mean survival was 24 months (range: 11-42 months), while patients without VEGF expression (n = 10, 58.9%) had a mean survival of 44 months (range: 21-60 months). CD117 expression was identified in only 2 out of 17 (1.17%) patients in our study. CONCLUSION: Our study evaluated the role of c-kit and VEGF overexpression in MCL. Although CD117 may not be of therapeutic significance, target-directed signal transduction inhibition therapy using VEGF-inhibitors may be a distinct possibility in a select group of patients with MCL. Future larger studies are urgently needed to elaborate the role of VEGF in MCL.

Adult↗
PubMedDate not supplied

Risk of primary non-hepatocellular malignancies in hereditary hemochromatosis.

OBJECTIVE: The relationship between hemochromatosis, a genetic iron disorder, and the risk of hepatocellular carcinoma is well-documented. However, the true incidence of non-hepatocellular malignancies remains ill defined. We performed a retrospective cohort study to identify a possible association between hereditary hemochromatosis and the development of non-hepatocellular carcinomas. MATERIALS AND METHODS: After appropriate institutional review board approval, an extensive chart review was completed on all patients with hereditary hemochromatosis diagnosed between 1986 and 2001. The diagnosis was based on either a genetic study to identify the Cys282Tyr and the His63Asp mutations on the HLA-H gene and/or hepatic tissue diagnosis, in conjunction with a treatment history of therapeutic phlebotomy. Data collection also included documentation of associated malignancies, the presence of co-morbid medical illnesses, and risk factors for cancer. Our database was age-standardized to the United States population using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program data to obtain a standardized incidence ratio (SIR) of non-hepatocellular malignancies in our study population. RESULTS: Fifty-nine patients (49 males, 10 females) with a mean age of 46 years (range: 10-68 years) met the criteria for the diagnosis of hereditary hemochromatosis. Of these, 13 patients (22%) had a biopsy-proven diagnosis of a primary non-hepatocellular malignancy giving an age-adjusted SIR of 1.40 (p < 0.04). Histologically, the types of malignancy included: 3 patients with colorectal cancer; 2 patients with gastric carcinoma, 3 patients with prostate cancer; 2 patients with breast cancer; 1 patient with acute myelogenous leukemia, one patient with Hodgkin's lymphoma and one patient with non-Hodgkin's lymphoma. CONCLUSION: While an association between hemochromatosis and hepatocellular carcinoma is well-described, there also appears to be a relationship between hemochromatosis and the development of non-hepatocellular malignancies. Since increased iron stores alone have not been proven to be premalignant in recent studies, interplay between genetic factors in hemochromatosis may play a role as a risk factor in the development of an associated malignancy. Larger cohorts of subjects with hereditary iron overload disorders are needed to confirm our findings. Furthermore, if a causal association between hemochromatosis and common carcinomas does indeed exist, such patients may be candidates for individualized, rigorous cancer screening programs.

Adolescent↗
PubMedDate not supplied

HER-2/neu and CD117 (C-kit) overexpression in hepatocellular and pancreatic carcinoma.

BACKGROUND: Hepatocellular carcinoma has an overall 5-year survival of less than 5%. Similarly, pancreatic cancer has a mortality: incidence ratio of 0.99. The aim of this study was to determine the prevalence of HER-2/neu and c-kit (CD117) overexpression and to identify a possible predictive role in patients with these two malignancies. MATERIALS AND METHODS: We performed a retrospective study on archival specimens of subjects with hepatocellular and pancreatic carcinoma. HER-2/neu and CD117 overexpression were evaluated by immunohistochemistry. RESULTS: Thirty-three patients with pancreatic carcinoma and 25 patients with hepatocellular carcinoma were identified. The mean age was 71.7 years for patients with pancreatic carcinoma and 66 years for patients with hepatocellular carcinoma. Two patients with hepatocellular carcinoma and none with pancreatic cancer overexpressed HER-2/neu, while 2 patients with pancreatic carcinoma and 1 patient with hepatocellular carcinoma overexpressed CD117. CONCLUSION: HER-2/neu and CD117 are not significantly overexpressed in either cancer. There appears to be no role for the use of trastuzumab in either malignancy. Similarly, while there appears to be no role for tyrosine kinase inhibitors in the treatment of hepatocellular carcinoma, further larger studies are necessary in pancreatic adenocarcinoma.

Adult↗
PubMedDate not supplied

Predictive value of absent bone marrow iron stores in the clinical diagnosis of iron deficiency anemia.

The examination of Prussian-blue-stained bone marrow aspirates for the presence or absence of histiocytic iron granules has been considered the gold standard in evaluating iron-depeleted states. We performed this study to evaluate the predictive accuracy of absent stainable bone marrow iron for iron deficiency anemia (IDA). A retrospective study was performed on an unselected series of 53 consecutive bone marrow biopsy specimens. Only those patients who had totally depleted iron stores and who had iron studies done within 6 months of bone marrow biopsy were included in the study. Based on these criteria, 12 patients were found eligible. After complete evaluation to determine the cause of the patient's illness, the final diagnosis was IDA in only 6 patients (50%). There was no significant difference between the two groups as regards hemoglobin level, reticulocyte count, serum iron levels, total iron binding capacity, red blood cell mean corpuscular volume, ferritin and the transferrin saturation levels. The finding of absent bone marrow iron stores is not necessarily predictive of iron deficiency anemia. The finding of absent stores of iron in the bone marrow needs to be taken in conjunction with other laboratory findings and the clinical scenario while making a diagnosis of IDA, since certain other hematological diseases may co-exist.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Immunohistochemical determination of vascular endothelial growth factor (VEGF) overexpression in malignant melanoma.

BACKGROUND: Molecular changes associated with the transition of melanoma cells from radial to vertical growth phase are not defined. To evaluate the role of VEGF in melanogenesis and determine its possible diagnostic and prognostic implications, we analyzed overexpression of VEGF in 202 cases of melanoma. MATERIALS AND METHODS: Overexpression of VEGF was evaluated in 202 archival paraffin-embedded tissue specimens using an avidin-biotin immunohistochemical (IHC) assay. RESULTS: Of the 202 melanoma specimens, 42 (20.8%) showed evidence of VEGF overexpression on IHC testing. Multivariate analysis performed using Cox proportional hazards method did not show a statistically significant survival difference between the VEGF-positive and negative groups (p = 0.25). CONCLUSION: Although of no significant prognostic value, VEGF may have critical therapeutic implications as a molecular target since it is expressed in about 20% of melanomas. The role of target-specific therapies against VEGF in malignant melanoma warrants further investigations.

Adolescent↗
PubMedDate not supplied

Immunohistochemical determination of HER-2/neu in malignant melanoma.

BACKGROUND: HER-2/neu onco-protein is increasingly being recognized as a target for therapy in solid tumors, but data on its role in malignant melanoma is currently limited. Our study objective was to determine a relationship, if any, between HER-2/neu overexpression and malignant melanoma. PATIENTS AND METHODS: Overexpression of HER-2/neu was evaluated in patients with malignant melanoma by using immunchistochemistry (DAKO Hercep test) in 202 archival tissue specimens. RESULTS: Between 1991 and 2001, 202 subjects [109 males; (54%) and 93 females; (46%)] with malignant melanoma were studied. Interestingly, only 2 of the 202 patients (0.9%) with biopsy-proven malignant melanoma revealed HER-2/neu overexpression. CONCLUSION: The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. Thus, there is no role for HER-2/neu testing in patients with malignant melanoma.

Adolescent↗
PubMedDate not supplied

Immunohistochemical detection of HER-2/neu, c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas.

PURPOSE: The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS. MATERIALS AND METHODS: We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system. RESULTS: Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03). CONCLUSION: VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.

Adolescent↗