Anti-cancer therapeutic agents and carpal tunnel syndrome: Clinical, electrodiagnostic, and ultrasound findings in seven patients.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and rarely develops after drug therapy. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in seven patients who experienced CTS due to anti-cancer therapeutic agents. METHODS: All patients underwent EDX testing, and four patients had an US study. RESULTS: CTS occurred in four patients with aromatase inhibitors, two with immune checkpoint inhibitors, and one with a selective estrogen receptor modulator. The mean duration between initiation of the anti-cancer therapeutic agents and symptom onset was 6 weeks (range: 2-12 weeks). Decreased digit sensation was noted in all patients; wasting and weakness of the abductor pollicis brevis (APB) was observed in three (42.8%) patients. The compound muscle action potentials (CMAP) of the APB and sensory nerve action potentials of the second or third digit could not be recorded in two (28.5%) and four (57.1%) patients, respectively. The needle EMG detected fibrillations and positive sharp waves in the APB in two patients. The motor unit potentials of the APB were decreased with large polyphasics in three (42.8%) patients. Of the four patients who underwent US testing, all had increased cross-sectional area of the median nerve at the carpal tunnel inlet, three (75%) had thenar muscle atrophy, and two (50%) had a loss of fascicular pattern. Three (42.8%) patients underwent a CTR. CONCLUSIONS: Physicians should be cognizant of the relationship between anti-cancer therapeutic agents and CTS. EDX studies and US play important roles in the diagnostic assessment of such patients.

Risk of occult spinal dysraphism based on lumbosacral cutaneous manifestations.

OBJECTIVES: Occult spinal dysraphism is a congenital failure of fusion of the posterior vertebral arches with intact skin overlying the defect. Lumbosacral cutaneous manifestations are associated with a variable risk of occult spinal dysraphism. Tethered cord syndrome is a type of occult spinal dysraphism that puts abnormal traction on the spinal cord. This study analyzed neonates and infants who were referred to our pediatric urology practice and had evidence of lumbosacral cutaneous manifestation on physical examination. METHODS: We reviewed the presence of lumbosacral cutaneous manifestations in neonates and infants evaluated in our pediatric urology clinic at our Institution over a 6-year period (1 March, 2015-28 February, 2021) with no prior diagnosis of lumbosacral cutaneous manifestation. All patients underwent a spinal ultrasound. RESULTS: The most common lumbosacral cutaneous manifestations were bifurcated/duplicated gluteal folds (33%), gluteal asymmetry (19%), and sacral dimples (14%). A total of 34 (24%) patients had an abnormal spinal ultrasound; 15 (44%) of these infants underwent a lumbar magnetic resonance imaging. A coccygeal pit was statistically marginally higher in abnormal versus normal spinal ultrasound (p = 0.07). Patients with only one lumbosacral cutaneous manifestation (N = 121) were significantly more likely to have a normal spinal ultrasound compared to those with two or more lumbosacral cutaneous manifestation (N = 17) (79% vs 53%, p = 0.03). CONCLUSION: Due to the varying risk of certain lumbosacral cutaneous manifestations with occult spinal dysraphism, all patients with a lumbosacral cutaneous manifestation should undergo spinal ultrasound. This study also highlights the importance of urodynamic studies when there are abnormal cutaneous findings. Routine physical examinations of the lumbar region for cutaneous manifestations of occult spinal dysraphism are vital to ensure prompt management of tethered cord syndrome and avoid potentially devastating consequences.

Risk assessment of preterm birth through identification and stratification of pregnancies using a real-time scoring algorithm.

INTRODUCTION: Preterm birth poses a significant challenge. This study evaluated a real-time scoring algorithm to identify and stratify pregnancies to indicate preterm birth. METHODS: All claims data of pregnant women were reviewed between 1 January 2014 and 31 October 2018 in Kentucky. RESULTS: A total of 29,166 unique women who were matched to a live newborn were documented, with the pregnancy identified during the first trimester in 54.1% of women. Negative predictive values, sensitivity, and positive likelihood ratios increased from the first to third trimesters as pregnant women who were matched to a live newborn had more visits with their physicians. The area under the receiving-operating characteristics curve on test data classifying preterm birth was 0.59 for pregnancies identified during the first trimester, 0.62 for pregnancies identified in the second trimester, and 0.73 for pregnancies identified in the third trimester. CONCLUSIONS: This study presents a real-time scoring algorithm of indicating preterm birth in the first trimester of gestation which permits stratification of pregnancies to provide more efficient early care management.

Concurrent renal cell carcinoma and hematologic malignancies: Nine case reports.

BACKGROUND: The presence of renal cell carcinoma (RCC) and hematologic malignancies (HM) in the same patient is rarely observed. Three primary findings have been described in these patients, including male gender and lymphoid malignancy predominance, and the HM are usually diagnosed before or simultaneously with the RCC. There is a lack of evidence about clinical outcomes in this setting. We report the common characteristics of 9 patients diagnosed with concurrent RCC and HM and their clinical course and response to treatment. CASE SUMMARY: Four (44%) patients were diagnosed with RCC prior to the HM, the diagnosis was simultaneous in 4 (44%) patients, and 1 (11%) patient was diagnosed with the HM prior to the RCC. No patients were treated with cytotoxic chemotherapy or radiation between the diagnosis of RCC and HM. Several unique features were seen in our case series, such as 3 simultaneous cancers in 1 (11%) patient, a splenectomy leading to remission of diffuse large B cell lymphoma without the use of chemotherapy in 1 (11%) patient, chemotherapy and rituximab for lymphoma resulting in a complete response in primary RCC in 1 (11%) patient, and immunotherapy providing an excellent response for primary renal leiomyosarcoma in 1 (11%) patient. CONCLUSION: These findings highlight the potential role of immune system dysregulation in patients with the diagnosis of RCC and HM whereby the first malignancy predisposes to the second through an immunomodulatory effect. HM have the potential of being confused with lymph node metastasis from kidney cancer. Lymph node biopsy may be necessary at the time of initial diagnosis or in cases of mixed response to therapy. Long-term medical surveillance is warranted when a patient is diagnosed with RCC or HM. Clinicians should be aware of the higher prevalence of male gender and lymphoid malignancy with concurrent RCC and HM and that either of these conditions may be diagnosed first or they may be diagnosed simultaneously.

Metastatic clear cell renal cell carcinoma in isolated retroperitoneal lymph node without evidence of primary tumor in kidneys: A case report.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) plays a diagnostic, therapeutic, and prognostic role in myriad urologic malignancies, including testicular carcinoma, renal cell carcinoma (RCC), and upper urinary tract urothelial carcinoma. RCC represents 2% of all cancers with approximately 25% of patients presenting with advanced disease. Clear cell RCC (CCRCC) is the most common RCC, accounting for 75%-80% of all RCC. CASE SUMMARY: A 71-year-old man presented with a history of benign prostatic hypertrophy. He was asymptomatic without any hematuria, pain, or other urinary symptoms. A computed tomography (CT) scan of the abdomen and pelvis showed a 1.8 cm left retroperitoneal lymph node. There was no evidence of renal pathology. A core biopsy was performed of the left para-aortic lymph node. Although the primary tumor site was unknown, the morphological and immunohistochemical features were most consistent with CCRCC. A RPLND was performed which revealed a single mass 5.5 cm in greatest dimension with extensive necrosis. The retroperitoneal lymph node was most compatible with CCRCC. A nephrectomy was not conducted as a renal mass had not been detected on any prior imaging studies. The patient did not receive any type of adjuvant therapy. The patient underwent surveillance with serial CT scans with contrast of the chest, abdomen, and pelvis for the next 5 years, all of which demonstrated no recurrent or metastatic disease and no evidence of retroperitoneal adenopathy. CONCLUSION: Our unique case emphasizes the therapeutic role of metastasectomy in metastatic CCRCC even in the absence of primary tumor in the kidneys.

Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery.

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

Improvement of therapeutic index for brain tumors with daily image guidance.

BACKGROUND: Image-guidance maximizes the therapeutic index of brain irradiation by decreasing setup uncertainty. As dose-volume data emerge defining the tolerance of critical normal structures responsible for neuroendocrine function and neurocognition, minimizing clinical target volume (CTV) to planning target volume (PTV) expansion of targets near these structures potentially lessens long-term toxicity. METHODS: We reviewed the treatment records of 29 patients with brain tumors, with a total of 517 fractions analyzed. The CTV was uniformly expanded by 3 mm to create the PTV for all cases. We determined the effect of patient specific factors (prescribed medications, weight gain, tumor location) and image-guidance technique on setup uncertainty and plotted the mean +/- standard deviation for each factor. ANOVA was used to determine significance between these factors on setup uncertainty. We determined the impact of applying the initial three fraction variation as custom PTV-expansion on dose to normal structures. RESULTS: The initial 3 mm margin encompassed 88% of all measured shifts from daily imaging for all fractions. There was no difference (p = n.s.) in average setup uncertainty between CBCT or kV imaging for all patients. Vertical, lateral, longitudinal, and 3D shifts were similar (p = n.s.) between days 1, 2, and 3 imaging and later fractions. Patients prescribed sedatives experienced increased setup uncertainty (p < 0.05), while weight gain, corticosteroid administration, and anti-seizure medication did not associate with increased setup uncertainty. Patients with targets near OAR with individualized margins led to decreased OAR dose. No reductions to targets occurred with individualized PTVs. CONCLUSIONS: Daily imaging allows application of individualized CTV expansion to reduce dose to OAR responsible for neurocognition, learning, and neuroendocrine function below doses shown to correlate with long-term morbidity. The demonstrated reduction in dose to OAR in this study has implications for quality of life and provides the motivation to pursue custom PTV expansion.