CANCER IN CHILDREN SOLID MODIFY STILL THE SLIDE By: Cecilia Galan- Fernandez, DPPS, DPSHBT, DPSPO Place: 5th floor ASMPH Date : January 11,2011 1

Cancer Pathogenesis Normally, your body forms new cells as you need them, replacing old cells that die All kinds of cancer, including childhood cancer, have a common disease process cells grow out of control, develop abnormal sizes and shapes ignore their typical boundaries inside the body destroy their neighbor cells spread (or metastasize) to other organs & tissues As cancer cells grow, they demand more nutrition from the body Cell cycle

Epidemiology Incidence 14/100,000 Among all age groups, the most common childhood cancers are leukemia, lymphoma, and brain cancer. As children enter their teen years, there is an increase in the incidence of osteosarcoma (bone cancer). The sites of cancer are different for each type

Risk Factors Pediatric vs. Adult Cancers Lifestyle factors that contribute to the development of cancer in adults: smoking diet obesity occupation prolonged exposure to carcinogenic agents

For the 0-14 yrs old Acute leukemias (ALL-most common) Central nervous system tumors Neuroblastoma Wilms’ tumor Non Hodgkin’s Lymphoma Rhabdomyosarcoma, soft tissue tumors,germ cell tumors, retinoblastoma and bone tumors For 15 – 19 yrs old Hodgkin’s disease Germ cell tumors Osteosarcoma, Ewing’s sarcoma

Risk Factors Pediatric vs. Adult Cancers Lifestyle factors are not associated with cancer in children Genetic condition- anomalies Family history Environmental- ionizing radiation, chemicals Infections – EBV Chemotherapy Precise cause – unknown

Signs of Childhood Cancer Continued, unexplained weight loss Headaches, often with early morning vomiting Increased swelling or persistent pain in bones, joints, back, or legs Lump or mass, esp. in the abdomen, neck, chest, pelvis, or armpits Development of excessive bruising, bleeding, or rash Constant/recurrent infections A whitish color behind the pupil Nausea which persists or vomiting with or w/o seizure Constant tiredness or noticeable paleness Eye or vision changes which occur suddenly and persists Recurrent or persistent fevers of unknown origin

WHY DIFFICULT TO DIAGNOSE CHILDHOOD CANCER? Vague manifestations Childhood malignancies are rare Doctor’s reluctance to consider cancer diagnosis

Important Factors to Cure EARLY DETECTION PROPER TREATMENT GOOD SUPPORTIVE CARE

RETINOBLASTOMA

RETINOBLASTOMA Most common intraocular malignancy of childhood 2nd most freq solid malignancy 80% are diagnosed before 3-4 years old Median age at diagnosis: 2 years old Beyond 6 years old is rare!!! Incidence: 1. 60% --non-heriditary & unilateral 2. 25% --hereditary & bilateral 3. 15% --hereditary & unilateral

CLASSIFICATION 1.Laterality ---unilateral or bilateral 2.Focality ---Unifocal or multifocal 3.Genetics --- hereditary or nonheriditary

LATERALITY UNILATERAL -Knudson’s two hit phenomenon -15% carry constitutional mutation BILATERAL -asstd. with advanced parental age -present earlier than unilateral -hereditary form -worse prognosis -autosomal dominant

Retinoblastoma RB gene on Chromosome 13, “two-hit theory” Round blue cell tumor arising in any of the nucleated layers of the retina Hematogenous, lymphatic spread, direct extension thru the optic nerve Only 10% detected by ophthalmologic screening 14

COMMON SIGNS & SYMPTOMS Leukokoria --most common Strabismus --2nd most common Decreased visual acuity Inflammatory changes Glaucoma Vitreous hemorrhage resulting in black pupil Rubeosis iridis –(neovascularization of surface of iris) *in 50% with advanced dsespontaneous bleed---hyphema

Investigations for Diagnosis of Retinoblastoma 1.Examinations -done under anesthesia by pedia ophtha -done by pedia oncologist -Audiology evaluation if chemo with carbplatin 2. Imaging studies -CT scan of brain and orbits 3. Laboratory evaluations -CBC,Bld chem,electrolytes -Creatinine clearance if chemo with carboplatin

Investigations for Diagnosis of Retinoblastoma 4. Diagnostic Studies -Lumbar puncture ---only if with radiographic or clinical suspicion of CNS disease -Bone scan --- only if with bone pain or other extra- ocular disease -Bone marrow biopsy –only with abnormal CBC(without alternative explanation) or other extraocular disease 5.Pathologic evaluation---if enucleation is performed

Histology: The only human tumor that is radically treated without tissue biopsy confirmation Flexner-Wintersteiner rosettes: lined by tall cuboidal cells that circumbscribe and an apical lumen

Patterns of Spread Intraocular: 1 Patterns of Spread Intraocular: 1. With endophytic growth, there is a white hazy mass. 2. With exophytic growth, there is retinal detachment. 3. Most tumors have combined growth. 4. Retinal cells frequently break off from the main mass and seed the vitreous or new locations on the retina.

Extraocular: Retinoblastoma spreads first to surrounding structures and then by hematogenous or lymphatic extension. Retinoblastoma invades the optic nerve. From there it can spread directly along the axons to the brain or may cross into the subarachnoid space and spread via the CSF to the brain. Hematogenous spread leads to metastatic disease, most commonly to brain, bone marrow, or bone. Lymphatic spread is rare because there is minimal lymphatic drainage of the orbit. Occasionally, retinoblastoma spreads lymphatically to the preauricular and submandibular nodes.

PARTS OF THE EYE

retinoblastoma

SITES OF METASTASIS BRAIN BONE BONE MARROW LUNGS

RISKS FOR METASTATIC SPREAD 1. If optic nerve stump is <5mm—bad >5mm---better 2. Tumor invasion into the anterior chamber 3. Large tumor with vitreous seeding 4. Rubeosis iridis 5. Glaucoma

Retinoblastoma Primary Goal: Cure!!!! GOAL OF TREATMENT: Primary Goal: Cure!!!! Secondary Goal: Preservation of vision 28

TREATMENT Surgery Enucleation—if no hope for salvage of useful vision II. Radiotherapy III. Chemotherapy

Neuroblastoma Most common extracranial solid tumor in infancy 8-10% of all childhood malignancies Affects infants & preschool 50% younger than 2 year old 30% younger than 1 year old

NEONATAL NEUROBLASTOMA Subcutaneous nodules. If massaged, a zone of pallor develops around the nodule due to catecholamine discharge Extensive metastasis to the liver Bone marrow involvement Massive adrenal hemorrhage into tumor Hydrops fetalis and/or signs of erythroblastosis fetalis Stage 4S Diagnosis: prenatal ULTZ In many cases, a mass is not palpable Only 50% have elevated urinary catecholamines Prognosis: favorable course (if with + favorable factors) Treatment: Curative by surgery Course: Others regress

NEUROBLASTOMA Originates from primordial neural crest cells that normally give rise to adrenal & sympathetic ganglia Are tumors of the sympathetic nerve tissue Can occur anywhere along the sympathetic neural pathway

Neuroblastoma – Clinical Features Arise from the sympathetic outflow Primary sites 70% abdominal primary (50% adrenal medulla, 50% extra-adrenal tissue) Thoracic tumours, posterior mediastinum (20%) Head & neck tumours (10%) Epidural (dumbbell or hourglass shaped) tumors – cord compression/paraplegia Bone Lymph nodes are enlarged Lungs—rarely involved(0.7%), involvement should be proven by bx Pelvis---constipation,urinary retention,presacral

MANIFESTIONS Excessive catecholamine (VMA/HVA) intermittent attacks of sweating,pallor Headaches,palpitation Hypertension—renin induced due to renovascular compromise & seen in 1-5%

MANIFESTATIONS 2. Signs & symptoms of Vasoactive Intestinal Peptide (VIP) Intractable watery diarrhea resulting to failure to thrive Abdominal distention hypokalemia

MANIFESTATIONS 3. Acute myoclonic encephalopathy Bursts of rapid involuntary random eye movements in all directions of gaze (OPSOCLONUS) Motor incoordination due to frequent,irregular jerking of muscles of the limbs and trunk (MYOCLONIC JERKING) Note: 1.May or may not resolve after the tumor is removed or symptoms may resolve only after several months. Some , it may be permanent 2. Prognosis is good

PATHOPHYSIOLOGY OF OM NOT DUE due to direct involvement of the CNS by tumor or due to the production of catecholamines It is associated by well-defined IgG & IgM autoantibodies that bind to the cytoplasm of cerebellar Purkinje cells & to some axons in the white matter Diffuse & extensive lymphocytic infiltration with lymphoid follicles is a characteristic histologic feature of OM This suggests an IMMUNE-MEDIATED MECHANISM OF THIS RARE SYNDROME

Recommended Criteria at INSS Conference for a Diagnosis of Neuroblastoma Established if: (1) Unequivocal pathologic diagnosisa is made from tumor tissue by light microscopy (with or without immunohistology, electron microscopy), and/or increased urine or serum catecholamines or metabolites.b OR (2) Bone marrow aspirate or trephine biopsy contains unequivocal tumor cellsa (e.g.,syncytia or immunocytologically positive clumps of cells) and increased urine or serum catecholamines or metabolites Source: Manual of Pediatric Hematology & Oncology (4th ed) p534

Recommended Studies for Assessment of Extent of Disease Tumor site Recommended tests Primary site CT and/or MRI scana with 3-D measurements; MIBG scan.b Metastatic sites Bone marrow Bilateral posterior iliac crest marrow aspirates and trephine core bone marrow biopsies required to exclude marrow involvement. A single positive site documents marrow involvement. Core biopsies must contain at least 1 cm of marrow (excluding cartilage) to be considered adequate. Bone MIBG scan; 99Tc scan required if MIBG scan negative or unavailable. Plain radiographs of positive lesions. Lymph nodes Clinical examination (palpable nodes confirmedhistologically. CT scan for nonpalpable nodes (3-D measurements). Abdomen/liver CT and/or MRI scana with 3-D measurements. Chest AP and lateral chest radiographs. CT/MRI necessary if chest radiograph positive, or if abdominal mass/nodes extend into chest

NB – Clinical features Metastases Bone marrow- anaemia Bone (Pain) Orbit (Peri-orbital Skin (blue-berry muffin)

NB – Therapy Surgery –laminectomy to decompression Chemotherapy-responsive in 80-85%;advantageous in making surgery safer by reduction of tumor size Transplant (Stage 4, Nmyc amplification HD Chemo with Autologous Bone Marrow Transplant

Evaluation of a Lymph Node A diagnosis of lymphoma or any malignancy must always be considered when evaluating a child with an enlarged peripheral lymph node It must be emphasized that not all palpable nodes are pathologically enlarged and that most pathologically enlarged nodes are benign. Points to consider in evaluating a lymph node: I. LOCATION OF THE NODE a. Nodes of the axilla, neck and groin are often palpable in normal children b. Palpable supraclavicular nodes -- always considered abnormal * if with left-sided (Virchow’s) – metastases from intra-abdominal CA * if with right-sided nodes --- intrathoracic disease

II When size matters a.Cervical and axillary nodes --- > 1 cm b. Inguinal node ------ >1.5 cm c. Epitrochlear node ----> 0.5 cm

IV.INDICATIONS III. GENERALIZED OR LOCALIZED? a. Generalized --- involvement of more than two (2) noncontiguous areas caused by many different disease process b. Localized ---- enlarged lymph nodes within contiguous anatomic regions and usually due to one of two ( infection or malignancy) III. CHARACTER Malignant nodes ---- non-tender, firm, rubbery and rapidly enlarging becoming cnonfluent and located in the supraclavicular region

INDICATIONS FOR LYMPH NODE BIOPSY Chronic,persistent,progressive adenopathy If an infectious etiology has not been uncovered, a dominant node that persists for 6 weeks should be biopsied . Node > 2.5 cm in diameter in the absence of signs of infection that warrant a trial of antibiotic Supraclavicular adenopathy Sytemic symptoms

Non-Hodgkin Lymphoma 5-7% malignant disease of childhood 3rd most common childhood malignancy 60% of childhood lymphomas M>F Peak age: 5-15 years old Etiology: unknown Risk factors: Genetic-- SCID, WAS Posttransplantation immunosuppression Drugs ex. Phenytoin (cause pseudolymphoma that regress with cessation of treatment) Radiation – treatment with radiotherapy (4-5% develop NHL within 10 years Virus---EBV and HIV

APPROACH TO THE DIAGNOSIS OF NON HODGKIN’S LYMPHOMA History and PE childhood lymphoma more often extranodal rapid tumor growth frequently involved site: Intra-abdominal ( B-cell) Intrathoracic (precursor T-cell) Sites: Abdomen --- primary site (35%) Head and neck ---- 13% Mediastinum ---- 26% CNS and BM --- CNS involvement and epidural tumor uncommon at presentation but more common in the presence of BM involvement. --- 2/3 with BM disease have simultaneous CNS involvement --- Intracranial tumor more likely epidural although it can occur within brain parencyma

B SYMPTOMS OF HODGKIN LYMPHOMA 1. Unexplained fever with temp above 38.0ْ C orally 2. Drenching night sweats 3. Unexplained weight loss of 10% within 6 months preceding diagnosis Source: Principles & Practice of Pediatric Oncology 5th ed p.701

IMPORTANT INVESTIGATIONS FOR NHL Histologic analysis- Primary mode of definitive diagnosis CBC and APC Chemistries and Serum electrolytes Liver and renal function tests SLDH- measures tumor volume Uric acid Imaging studies Chest X-ray Chest CT Abdominal CT/ Ultrasound BMA with biopsy ( bilateral) CSF examination -- essential

ST. JUDE CHILDREN’S STAGING SYSTEM STAGE I A single tumor (extranodal) or single anatomic area (nodal) with the exclusion of mediastinum or abdomen STAGE II A single tumor (extranodal) with regional node involvement Two or more nodal areas on the same side of the diaphragm Two single (extranodal) tumors with or without regional node involvement on the same side of the diaghragm A primary gastrointestinal tract tumor, usually in the ileocecalarea, with or without involvement of associated mesenteric nodes only STAGE III Two single tumors (extranodal) on opposite sides of the diaphragm Two or more nodal areas above and below the diaphragm All the primary intrathoracic tumors (mediastinal, pleural and thymic) All extensive primary intraabdominal disease All paraspinal or epidural tumors, regardless of other tumor site(s) STAGE IV Any of the above with initial CNS and/or bone marrow involvement

Lymphomas – 3rd most common Hodgkin Lymphoma Childhood form < 14yo, young adult form 15-34yo, older adult form 55-74yo EBV implicated, <10 yrs, male, with preexisting immunodeficiency Reed-Sternberg cell hallmark of disease Painless lymphadenopathy, anterior mediastinal mass and systemic symptoms like fever, night sweats and weight loss Ann Arbor Staging System Same + neck CT, ESR, serum copper and ferritin Non- Hodgkin Lymphoma Classified as B or non-B types (previously classified as lymphoblastic, SNCCL, LCL) Intrathoracic, abdominal skin , bone, soft tissues, CNS St Jude Staging system CBC, electrolytes, uric acid, sldh, creatinine, sgpt,chest Xray or scan, abdominal scan or MRI, bone scan, BMA or biopsy, CSF cytology 51

WILMS’ TUMOR Most common primary malignant tumor of childhood EPIDEMIOLOGY: 1975-1995 – 7.6 Cases per million children younger than 15 y/o 6% of childhood cancer higher for blacks, low in Asians F>M

A CHILD WITH ANIRIDIA Wilms’ tumor associated syndrome (WAGR) 2.Hemihypertrophy 3.Genitourinary abnormalities 4. Mental retardation

Wilm’s Tumor (Nephroblastoma) Clinical Features: 1.Abdominal mass -Synchronous (4.4-7%) -Metachronous(1-1.9%) 2.Abdominal pain 3. Hematuria (10%) 4.Hypertension (25%)

PHYSICAL EXAMINATION Location Size of the mass Note: WT is usually a large flank mass that does not particularly move with respiration.

WORKUP CBC Liver tests Renal function tests (urinalysis,creatinine) Serum calcium (elev.in rhabdoid or cmn) Coagulation assays Imaging studies: CT (abdomen) Doppler ULTZ –to assess the IVC CXR/ CT (chest) Bone scan or skeletal survey Brain imaging (MRI)

STAGING (NWTS-5) Stage I ---confined to the kidney & completelyresected. no renal capsule penetration or involvement of renal sinus vessel Stage II --- tumor extends beyond the kidney but completely resected (neg.margins & LN) At least 1 of the ff: a. Penetration of the renal capsule b. Invasion of renal sinus vessels c. biopsy of tumor prior to removal

STAGING (NWHTS-5) (lung,liver,bone,brain) STAGE III --- Gross or microscopic residual tumor remains postop,including inoperable tumor spillage of tumor preop or intraop regional LN metastasis or transected tumor thrombus STAGE IV ---- Hematogenous or LN mets outside the abdomen (lung,liver,bone,brain) STAGE V ----- Bilateral Wilms’ tumor

Predictive factors (recurrence/progression 1.size 2.age of patient 3.histology a .blastemal– hi stage/invasive b. stromal c. epithelial –low stage/ less invasive and resistant to chemotx

PROGNOSIS 4. LN metastasis 5. local features of tumor – capsular or vascular invasion IMPORTANT: The histologic finding of ANAPLASIA is the most important determinant prognosis

BILATERAL WILMS’ TUMOR Histology: favorable Prognostic factors: 1. Age diagnosis at early age (<2 y/o) –better survival rate: <2 y/o ---70-75% >2 y/o --- 20-45% 2. Stage Stage 1 & II ---85% Stage III & IV --- 0%

POSITIVE PROGNOSTIC FACTORS Stage I an II 2. Neg. Para-oartic nodes 3. Absence of anaplasia/sarcomatous 4. Absence of tumor rupture 5. Time of relapse (later better than early) (> 15 months from diagnosis) 6. Site of metastases at relapse (Lung better than liver)

NEPHROGENIC RESTS

TREATMENT 2. Tumor removal by partial nephrectomy OBJECTIVE: 1. Maximum preservation of renal tissue 2. Tumor removal by partial nephrectomy

TREATMENT Laparotomy and bx of both kidneys (stage and histology) LN should be bx & each side is staged separately. Excision of the tumor(s) is performed at the initial operation only if all of the tumor can be removed with preservation of sufficient renal parenchyma for normal renal function on at least one side Chemotherapy Babies < 12 mo.– half the dose Babies > 12 mo.– full dose

CHEMOTHERAPY DOSE: A- Dactinomycin (45ug/kg,IV) D* Doxorubicin (1.0mg/kg, IV) D # Doxorubicin (1.5mg/kg,IV) V – Vincristine(0.05mg/kg,IV) V* Vincristine(0.67mg/kg,IV) XRT – Radiation therapy ** for StageIII and IV, FH or StageII-IV,UH

TREATMENT Evaluation and Abdominal CT – at week 5 at wk 6 – if the imaging showed persistent but resectable tumor or tumor responded completely do second look surgery and biopsy at 2nd look surgery ---complete excision of the tumor frm.the least involved kidney shld. be carried out. If the procedure leaves a viable & functioning kidney on 1 side & the other kidney, if extensively involved with tumor, should be removed.

TREATMENT Postoperative chemo shld. be adapted to renal function abnormalities: a.If 2nd look surgery showed no gross or pathologic evidence of persistent tumor, chemo be given accordingly b. If 2nd look surgery showed gross or pathologic evidence of persistence that can’t be resected, do radiotx and change chemo (ICE)

Abdominal Tumors Neuroblastoma Wilms’ tumor – 2nd Peripheral sympathetic nervous system malignancy <5 yrs old, median 2 years old, male predominance Most common abdominal malignancy Shimada classification, MYC gene Retroperitoneal, palpable causing abdominal discomfort, opsomyoclonus, diarrhea (+) calcification and hemorrhage on CT Bone, marrow liver, nodes skin mets Wilms’ tumor – 2nd Nephroblastoma or mixed embryonal neoplasm of the kidney with three elements: blastema, epithelia and stroma 2-5 years of age WT1 gene (11p13) Denys-Drash syndrome, WT2 gene Beckwith-Wiedenman syndrome, GUT abn Smooth and firm, pain, vomiting and hematuria, hypertension (-) calcification Pulmonary metastasis, nodes 69

Abdominal Tumors Neuroblastoma Wilms’ tumor – 2nd CT or MRI, BMA, bone scan, urine VMA and HVA (95% +) Prognostic factors: age at diagnosis, stage, MYCN status, Shimada histology and ploidy in infants Stage IV-S: <1year old, with dissemination to the skin, liver, bone marrow without bone involvement plus a primary tumor Wilms’ tumor – 2nd CT or MRI and chest XRay Prognosis affected by stage and type of histology, unfavoprable in the presence of large nuclei, hyperchromatism, multiple mitotic figures Stage V – bilateral tumors 70

HEPATOBLASTOMA

Liver Tumours Hepatomegaly ± jaundice Raised AFP (age-specific normogram) 2 types: Hepatoblastoma most common infants & young children Hepatocellular carcinoma Rare, older HBV, HCV

Rhabdomyosarcoma Most common soft tissue sarcoma Found in any anatomic site: head/neck (40%), GUT (20%), trunk (10%) Associated with Li Fraumeni syndrome and Neurofibromatosis Arise from the same embryonic mesenchyme as striated muscle Types: embryonal (60%) intermediate prognosis boytryoid, alveolar, pleomorphic, undifferentiated 73

Clinical Non-tender mass with no unusual hue to the overlying skin or subcutaneous tissue Growth of a nontender mass esp. without a clearcut history of trauma, should always alert the MD to consider biopsy, esp. if expansion is confirmed by repeated observations over 1-2 weeks Mass within a body cavity producing obstruction or discharge,mandates a biopsy

Rhabdomyosarcoma Diagnosis: disseminates early CT/MRI, BMA, bone scans, lymph node biopsy The most essential element of the work-up is examination of the tumor tissue w/c include the use of special stains(desmin, muscle specific actin, MyoD). Completely excised tumors have the best prognosis. Favorable site: orbit older children and disseminated diseases have poorer prognosis 75

Rhabdomyosarcoma Sites Head & neck Orbit, nasopharyngeal & middle ear tumours Genitourinary tract Bladder & prostate, vaginal & uterine Extremity Prognosis Orbit - excellent GU tract - good Extremity, retroperitoneal, metastatic - poor

Bone Tumours

Malignant Bone Tumors Osteosarcoma Ewing’s Sarcoma Most common primary malignant bone tumors in children Second decade of life, growth spurt, long bones, metaphysis Pleomorphic, spindle shaped cells with malignant osteoid Bone pain and swelling “Sunburst pattern” xray Primary site: FEMUR (metaphyseal portion) Long bones Ewing’s Sarcoma More common in the first 10 years of life Small round undifferentiated tumors of neural crest origin, flat bones, diaphysis Askin tumor –if tumors arise in the chest wall S100 and NSE (+) Pain and swelling, (+) fever and weight loss “onion-skinning” pattern xray (flat & diaphyses) Primary: pelvic,LE,bones of chest wall 78

Radiological difference Sunburst of Osteosarcoma Onion skin of Ewings sarcoma

Malignant Bone tumors Diagnosis: MRI or CT of tumor SLDH bone scan Alkaline phosphatase chest ct scan bone biopsy/BMA in Ewing’s Sarcoma Both with 75% cure rate if non-metastatic on presentation. Treatment: Multi-agent chemotherapy and surgery. Radiotherapy also needed in Ewing’s Sarcoma 80

Brain Tumours Special problems Blood-brain barrier limits chemotherapy Developing brain is vulnerable to toxicity of therapy Proximity of tumours to vital structures precludes extensive surgery Tendency to spread within neuraxis

Brain Tumours - Classification Location 2/3 above & 1/3 below tentorium

Site and symptoms Posterior fossa – limited space, disrupt CSF flow Vomiting, Increased ICP Motor tract involvement – cranial n, long tracts Supratentorial Seizures – focal seizures Deterioration in school performance Hormonal defects – central precocity, diabetes insipidus

(L) parieto-occipital low grade astrocytoma

Brain Tumours - Therapy Surgery Resectability Radiotherapy Toxicity IQ drop Endocrinopathy Growth failure Chemotherapy Prolong survival Increase cure rates Prognosis depends on: Resectability Age Metastases Chemosensitivity Prognosis depends on Resectability Age Metastases Chemosensitivity 85

Oncologic emergencies Tumour lysis syndrome

Tumour lysis syndrome Metabolic derangement resulting from rapid death of malignant cells Must have 2 important factors : high tumour burden, highly sensitive tumour – ALL, AML, NHL Hyperkalaemia - hydration, no K supplements, K binders Hyperuricaemia – hydration, alkalinisation, allopurinol, uricozyme to convert to allantoin Hyperphosphataemia – Phosphate binders Hypocalcaemia – if symptomatic, partial correction

Thank You!!! 88