Impact of Surgical Timing (Primary, Delayed, or Second Look) on Surgical Morbidity and Outcomes in Malignant Germ Cell Tumor of the Ovary in Children.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCT) are rare in children. Surgery with or without chemotherapy is the primary treatment approach. This study aimed to analyze the impact of primary and delayed surgery on surgical morbidity and outcomes. Second-look surgery after inadequate surgical staging and the various components of surgical staging were also evaluated. METHODS: Children below 15 years with MOGCT treated between 2006 and 2022 were analyzed. A comparison of patients undergoing primary, delayed, and second-look surgery was performed. RESULTS: 118 patients with a median age of 12 (0.11-15) years were eligible. Forty patients underwent primary, 51 delayed, and 27 second-look surgeries. Overall complications, including tumor rupture, blood loss, and adjacent organ removal, were significantly higher in the primary compared to the delayed surgery group (p = 0.0001). Second-look surgery conceded more blood loss (p = 0.0001), extended duration (p = 0.03), and complications (p = 0.004) than delayed surgery. The compliance with surgical guidelines was 100% for most components, with a positive yield rate of 10-80%. At a median follow-up of 5.2 years, the 5-year event-free survival (EFS) and overall survival (OS) for the entire cohort are 86% and 89%, respectively. The OS and EFS did not differ by the timing of surgery, although the second-look surgery demonstrated relatively inferior outcomes consequential to initial suboptimal surgery. CONCLUSIONS: MOGCT shows favorable outcomes. Delayed surgery after chemotherapy in appropriately selected patients minimizes the morbidity of surgery with similar outcomes compared to primary surgery. An optimal initial surgery is essential since second-look surgery produces significant morbidity. Prognosis Study, Level II evidence.

Role of imaging in the management of thyroglossal duct cyst carcinomas (TGC-TIRADS): a single centre retrospective study over 16 years.

Introduction: Thyroglossal duct cyst (TGDC) is the most frequently encountered developmental anomaly in thyroid genesis with a reported incidence of 7% in the adult population. The cyst is known to develop anywhere along the pathway of thyroid descent but is more frequently seen in the infrahyoid neck in the midline. The incidence of malignancy in a TGDC is approximately 1%; a majority of these are papillary carcinomas. This study was conducted at a single tertiary care centre which spanned over a decade which adds practice changing evidence-based knowledge to existing literature on this rare entity. A comprehensive study which conclusively establishes the imaging features predictive of malignancy in TGDC carcinomas (TGDCa), the protocol for optimal management, clinical outcome and long-term survival of these patients is not available. Although TGDC carcinoma is thought to have an excellent prognosis, there is not enough data available on the long-term survival of these patients. The aim of this study was to identify whether neck ultrasound (US) can serve as an accurate imaging tool for the preoperative diagnosis of TGDC carcinomas. Methods: We accessed the electronic medical records of 86 patients with TGDC between January 2005 to December 2021. Of these, 22 patients were detected with TGDC papillary carcinoma on histopathologic examination. Relevant imaging, treatment and follow up information for all cases of TGDC carcinoma were retrospectively reviewed. We compared US characteristics predictive of malignancy across outcomes groups; malignant vs benign using the Chi-square test. Based on the results, a TGC-TIRADS classification was proposed with calculation of the percentage likelihood of malignancy for each category. Results: Compared to benign TGDCs, malignant TGDCs were more likely to present with following US characteristics: irregular or lobulated margins (90.40 vs. 38.10%), solid-cystic composition (61.90 vs. 17.07%), internal vascularity (47.62 vs. 4.88 %), internal calcification (76.19 vs. 7.32 %) (each p value < 0.005). Calcifications and internal vascularity were the most specific while irregular/lobulated margins were the most sensitive feature for malignancy. AUC under the ROC curve was 0.88. Allpatients were operated and were disease free at the end of 5 years or till the recent follow up. Discussion: US is the imaging modality of choice for pre-operative diagnosis of TGDC carcinoma. Thepre-operative diagnosis and risk stratification of thyroglossal lesions will be aided by the application of the proposed TGC-TIRADS classification, for which the percentage likelihood of malignancy correlated well with the results in our study. Sistrunk procedure is adequate for isolated TGDC carcinoma; suspicious neck nodes on imaging also necessitates selective nodal dissection. Papillary carcinomas have an excellent prognosis with low incidence of disease recurrence.

Intracranial disease in pediatric Hodgkin lymphoma-case report and review of literature.

Central nervous system (CNS) involvement in Hodgkin lymphoma (HL) is an extremely rare presentation with dismal outcomes according to reported literature. An 8-year-old girl presented to us with complaints of on-off fever, right cervical swelling and bilateral ptosis. Positron emission tomography (PET) showed intracranial extra-axial soft tissue masses in right infero-lateral temporal lobe, sella and bilateral parasellar region along with cervical, mediastinal, axillary, abdominal and inguino-pelvic nodes, liver lesions and extensive marrow lesions involving the axial and appendicular skeleton. Histopathology of the cervical lymph node revealed a diagnosis of classical Hodgkin lymphoma. Child received 2 cycles of OEPA and 4 cycles of COPP followed by radiotherapy to bulky cervical lymph nodes and intracranial lesion. The child has been disease-free for 44 months with no neurological sequalae. Intracranial spread is rare in Hodgkin lymphoma and is associated with inferior outcomes. Due to its rarity, there are no specific treatment guidelines for this entity. The choice of ideal chemotherapeutic agents and role of whole-brain radiotherapy needs further evaluation.

Clinico-radiological profile, management and follow-up of methotrexate induced neurotoxicity in children with acute lymphoblastic leukemia.

Methotrexate-induced neurotoxicity is a well-defined side-effect of high-dose and intrathecal methotrexate with characteristic clinico-radiological findings and transient nature. Our experience in managing this entity in children with acute lymphoblastic leukemia(ALL) is reported here. All children with de novo ALLregistered from January 2016 through December 2021 who developed methotrexate-induced neurotoxicity were included. Of children with ALL treated during the study period, thirty-three experienced methotrexate induced neurotoxicity with an incidence of 1.25%. Stroke-like symptoms(36.36%; 12/33) were the most common clinical manifestation followed by seizures(30.3%, 10/33). Twenty-three patients had radiological features consistent with methotrexate-induced leukoencephalopathy. With emerging evidence, thirty-one patients were re-challenged with methotrexate (IV/IT), of whom 4 patients had recurrence of symptoms. No long-term neurological sequalae were noted in our cohort, despite rechallenging. Therefore in our study, methotrexate induced neurotoxicity is a self-limiting toxicity and methotrexate can be re-challenged safely without compromising theintensity of CNS-directed therapy.

MR imaging-based risk stratification scoring system to predict clinical outcomes in carotid body tumors.

Objectives: This study aims to evaluate the role of pretherapy MRI in predicting outcomes in carotid body tumors and propose a grading system for high- and low-risk characteristics. Materials and methods: A retrospective observational study of 44 patients with 51 lesions was carried out from year 2005 to 2020. MR images were reviewed for characteristics of carotid body tumor, and a score was given that was correlated with intra- and postoperative findings. The various other classifications and our proposed Mahajan classification were compared with Shamblin's classification. The area under the curve and ROC curves were used to present the accuracy of different predictive models. Results: Our scoring system allotted a score of 0 to 15 on the basis of MRI characteristics, with scores calculated for patients in our study ranging from 0 to 13. Lesions with scores of 0-6 were considered low risk (45%), and scores of 7-15 were regarded as high risk for surgery (55%). The Mahajan classification stages tumors into four grades: I (10%), II (20%), IIIa (8%), and IIIb (62%). The frequency of vascular injury was 50% in category I and 64% in category IIIb. The frequency of cranial nerve injury was 50%, 66%, and 27% in categories I, II, and IIIb. Conclusion: The Mahajan classification of CBTs evaluates high-risk factors like the distance of the tumor from the skull base and the angle of contact with ICA, which form the major predictors of neurovascular damage and morbidity associated with its surgery. Though the Shamblin classification of CBT is the most widely accepted classification, our proposed Mahajan classification system provides an imaging-based alternative to prognosticate surgical candidates preoperatively.

Factors Influencing Cervical Lymph Node Metastasis in Pediatric Differentiated Thyroid Cancers.

Lymph node metastasis is a considerable variable influencing postoperative American Thyroid Association (ATA) risk stratification in pediatric differentiated thyroid cancer (DTC). The primary aim of this study was to ascertain the factors predicting nodal metastasis and describe the outcomes in relation to the ATA risk. Patients 18 years or younger operated between December 2005 and December 2019 were analyzed. Demographic, clinicopathological, treatment, and outcome data were recorded. Factors associated with nodal metastasis were assessed by univariate and multivariate regression analysis. Patients were stratified into low-, intermediate-, and high-risk as per the pediatric ATA guidelines. A total of 86 patients (43% male; median [IQR] age, 12 (10-14) years) underwent surgery during the study period. Lymph node metastases were present in 70 (82.4%) patients involving the lateral (8%) and central compartment (4.7%) alone and both (88.6%) compartments. Extrathyroid extension (ETE) was present in 65%; 35%, minimal; and 30%, extensive. On univariate analysis, nodal metastasis was more frequent in male patients, multifocal tumor, lymphovascular invasion, and ETE. On multivariate analysis, only ETE was predictive of nodal disease with an odds ratio of 8. Minimal and extensive ETEs were both significantly associated with lymph node metastases when compared to the absence of ETE. The 5-year disease-free survival was 100%, 95.7%, and 66% in the low-, intermediate-, and high-risk groups respectively (p < 0.0001). Pediatric DTCs have an exceptionally high incidence of lymph node metastasis. ETE is the single most important predictor of nodal disease. The ATA pediatric risk stratification is useful in predicting clinical outcomes.

Feasibility of Nonanatomical Liver Resection in Diligently Selected Patients with Hepatoblastoma and Comparison of Outcomes with Anatomic Resection.

INTRODUCTION: Treatment guidelines for hepatoblastoma discourage nonanatomic liver resections. However, the evidence for this is inadequate and comes from a study performed almost two decades ago which additionally contained inherent limitations. This study aimed to assess the feasibility and oncologic outcomes of nonanatomic resections (NAR) performed in diligently selected patients and compare the results with anatomic resections (AR). MATERIALS AND METHODS: A total of 120 patients who underwent liver resections for hepatoblastoma between January 2008 and July 2019 were reviewed. Feasibility of NAR was based on postchemotherapy relations to vessels, site of the lesion, and possibility of achieving negative resection margins. RESULTS: AR was performed in 95 patients and 25 had NAR. The NAR cohort had similar International Childhood Liver Tumors Strategy Group (SIOPEL) risk group distribution. Blood loss and operative times were lower in patients undergoing NAR. No differences were noted between the two groups concerning postoperative morbidity and hospitalization. There were no pathologic positive margins or local recurrences in the NAR patients. Relapse free (RFS) and overall survival (OS) was similar in the two groups (p = 0.54 and 0.96, respectively). Subgroup analysis of only posttreatment extent of tumor (POSTTEXT) I and II patients also showed no difference in RFS or OS for the two groups with a persistent significant difference in operative times and blood loss. CONCLUSION: NAR is feasible with clear margins in carefully selected patients. It is not associated with more complications and outcomes are not inferior to AR. NAR is associated with lesser blood loss and operative time.

Intravascular extension of Wilms tumor: Characteristics of tumor thrombus and their impact on outcomes.

BACKGROUND: Studies describing intravascular involvement in Wilms tumor have focused on illustrating individual institutional experience and the elements of surgical management. Thrombus characteristics like extent, patterns of regression, and correlation with the surgical findings, intraluminal adhesion, and viable tumor in the thrombus, and patency of the inferior vena cava (IVC) have not been systematically described. OBJECTIVES: The aim of this study is to evaluate these thrombus characteristics and explore their impact on the overall outcomes. METHODS: All patients with histologically confirmed Wilms tumors with intravascular thrombus diagnosed in the pediatric oncology unit of Tata Memorial Hospital registered from 2006 to 2019 were included. Data regarding clinical, radiological, and surgical particulars were retrieved from the prospectively maintained institutional database. Specific data for the thrombus included: distal extent before and after neoadjuvant chemotherapy, correlation of extent with the surgical findings, completeness of thrombectomy, the presence of a viable tumor in the thrombus, and the patency of the IVC. Survival analysis was performed utilizing the Kaplan-Meier method on SPSS software version 25. RESULTS: The study included 43 (9.9%) of the 432 patients with Wilms tumor having intravascular extension. Retrohepatic IVC (33.3%) followed by atrioventricular (26%) formed the frequent levels of thrombus with maximum regression occurring after chemotherapy in the latter (Summary figure). The overall concordance rate between computed tomography (CT) scan and surgical findings for the presence of thrombus was 86% and 4 patients had the thrombus limited to a lower level than the preoperative scan. At a median follow-up of 5-years, the 5-year event-free and overall survival was 81% and 82.2% respectively. Atrioventricular thrombus (p = 0.003) and postoperative patency of IVC (p = 0.02) were significantly associated with inferior survival, while the extent of regression, thrombus fracture, and viability was not significant. DISCUSSION: The findings of this study bring forth the characteristics of intravascular tumor thrombus affecting the outcomes which can be validated in future prospective studies. Although the ideal method for radiological assessment of the intravascular thrombus is elusive, CT scan provided adequate information for the presence and level of the intravascular thrombus with reasonable accuracy in this study. Study limitations include small sample size, the limited number of events, and lack of multivariate analysis to rule out confounding factors that could influence the observed findings. CONCLUSION: Atrioventricular thrombus and occlusion of IVC represent adverse prognostic factors. The extent of regression, fracture, and viability of thrombus did not affect survival in this study.

Accuracy of MRI for nodal restaging in rectal cancer: a retrospective study of 166 cases.

AIM: Assessing metastatic mesorectal nodal involvement is a challenge in rectal cancer, especially in the post chemoradiation setting. We aim to assess the accuracy of MRI for nodal restaging and the validity of SAR criteria (≥ 5 mm size being metastatic). MATERIALS AND METHODS: This was an IRB-approved retrospective study of 166 patients with locally advanced rectal cancers, operated after neoadjuvant treatment. Two dedicated oncoradiologists reviewed the 166 post-chemoradiation presurgical MRIs in consensus. Nodal size and morphology (shape, margins, and signal intensity) were noted. The most accurate cut-off for size for predicting positive pN status was determined using the Youden index. RESULTS: MRI understaged 30/166 (18%) and overstaged 40/166 (24%) patients using the SAR criteria. The most accurate cut-off for node size was 5.5 mm, with a sensitivity of 75%, specificity of 60.2%, PPV of 40.7%, NPV of 86.9% (95% CI:78-92.5%), accuracy of 64.2%, and area under the curve (AUC) 0.657 (95% CI-0.524-0.79). Morphological characteristics were not significant to determine involvement, with positive nodes including 42% of round and 31% of oval nodes, 40% of heterogeneous and 45% of homogeneous nodes, and 31% irregularly marginated and 46% nodes with regular margins being positive on pathology. MRI was accurate in predicting pathology for mucinous nodes in 9/29 (31%) cases. Seven cases which were yN2 on MRI and yN0 on pathology demonstrated mucinous changes on MRI and had acellular mucin on histopathology. CONCLUSIONS: MRI has good negative predictive value, poor positive predictive value and moderate accuracy in nodal restaging. The cut-off of 5.5 mm demonstrated in our study is close to the SAR cut-off of 5 mm in the post-treatment setting. MRI accuracy is lower in patients with mucinous nodes.

Standardizing lymph nodal sampling for Wilms tumor: A feasibility study with outcomes.

BACKGROUND: Despite being mandated by cooperative groups, omission of nodal sampling is the most frequent protocol deviation in surgery for Wilms tumor. The stations as well as the number of nodes that should be sampled are not clearly defined resulting in a marked variation in practices among surgeons. We propose a systematic method for nodal sampling intending to reduce interoperator variation. In this study, we have assessed the feasibility and yield of systematic lymph node sampling and also evaluated the factors influencing nodal metastasis. METHODS: Prospective evaluation of 113 Wilms tumor patients operated at a single tertiary cancer center between 2015 and 2019. All these patients underwent a systematic 5-station nodal sampling. RESULTS: Median lymph node yield was 8 and 13.2% (15/113) patients harbored a histologically positive nodal disease. Of the patients with positive nodal disease, interaortocaval nodes had metastasis in 46.7% (n = 7). They represented isolated sites of nodal disease (skip metastases) in 28.6% (n = 4) of patients. Right-sided tumors had more frequent involvement of interaortocaval nodes and skip disease. Tumors with high-risk histology had 12.5 times more odds of harboring nodal disease as compared to low and intermediate-risk histology Wilms tumor. CONCLUSIONS: The proposed method of systematic station wise sampling provides a template to guide surgeons in performing lymph node harvesting. Interaortocaval nodes sampling should be performed routinely as the incidence of disease at this station is sufficiently high and metastasis may skip hilar nodes. STUDY OF DIAGNOSTIC TEST: Level III evidence.

Incidence, treatment, and outcomes of primary and recurrent Non-Wilms renal tumors in children: Report of 109 patients treated at a single institution.

INTRODUCTION: Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts. OBJECTIVE: To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India. METHODS: All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0. RESULTS: Of the 569 patients with renal tumors, 109 (19%) patients with primary (n = 97) or recurrent (n = 12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months. CONCLUSIONS: Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment.

Limb sparing surgery with vascular reconstruction for nonrhabdomyosarcoma soft tissue sarcoma in infants: A novel solution using allogenic vein graft from the parent.

Surgery continues to remain an integral component of treatment, especially for nonrhabdomyosarcoma soft tissue sarcoma as compared to rhabdomyosarcoma owing to their general insensitivity to chemotherapy. A key determinant of outcomes, particularly for extremity tumors includes complete tumor resection with negative margins; however, a significant limitation for limb salvage surgery is the adherence of sarcomas to vital vascular structures. Hitherto, vascular involvement constituted an adequate reason for amputation. However, modern reconstructive techniques and availability of prosthetic grafts in addition to autologous venous grafts have rendered limb salvage surgery possible in a substantial majority of patients. Vascular resection and reconstruction for extremity soft tissue sarcoma in children have not been used routinely for reasons like the small-caliber of native vessels, limited options for conduits and rapid somatic growth. The situation is inconceivable in infants owing to the contemporaneous diminutive caliber of the vessels. We report two infants with lower extremity nonrhabdomyosarcoma soft tissue sarcoma who underwent limb salvage surgery with resection of femoral vessels following which vascular reconstruction was successfully performed using the great saphenous vein allograft harvested from the father.