Bill Chiu

How Does the Operative Strategy for Primary Hyperparathyroidism Impact the Findings and Cure Rate? A Comparison of 800 Parathyroidectomies

BACKGROUND We hypothesized that a higher frequency of multigland disease and higher cure rate would result if routine four-gland exploration (4GL) was used as compared with focused parathyroidectomy (FP) for treatment of primary hyperparathyroidism. STUDY DESIGN During a 5-year period, data from two academic endocrine surgical practices were retrospectively reviewed for patients having an operation for primary hyperparathyroidism. Three hundred ninety-five consecutive patients underwent 4GL at one institution (A), and 405 consecutive patients underwent FP with selective use of 4GL at the other institution (B). The main outcomes measures were gender, preoperative imaging, surgical findings, gland weight, and operative success. RESULTS Three hundred ten (78%) patients at institution A were women, and 292 (72%) at institution B were women (p < 0.05). Routine 4GL strategy at institution A yielded a 16.5% frequency of multigland disease; and an FP strategy at institution B yielded 11.1% multigland disease (p = 0.028). At both institutions, single adenomas weighed more than multigland disease. Gland weights were not significantly different between the two institutions. Nine of 395 (2.3%) patients at institution A remained hypercalcemic postoperatively compared with 15 of 405 (3.7%) at B (p = 0.24; not significant). CONCLUSIONS A greater frequency of multigland disease was found with routine 4GL. There was no statistically significant difference in operative success between the two approaches. Sound surgical technique and intraoperative judgment, including interpretation of intraoperative parathyroid hormone values, will result in a high success rate, regardless of the operative strategy chosen for primary hyperparathyroidism.

Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model

Background:Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth.Methods:We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm3, 80–90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 μg doxorubicin (100IR), controlled-release film with 200 μg (200CR) over residual tumour bed; and 100 and 200 μg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed.Results:Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm3 after 28 days, 2200±290 mm3 after 35 days, 1280±260 mm3 after 63 days, and 1700±360 mm3 after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001–0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells.Conclusions:Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control.

Closing arguments for gastroschisis: management with silo reduction.

Abstract Background: There are two approaches to close gastroschisis. Primary closure (PC) is reduction and fascial closure; silo closure (SC) places viscera in a preformed-silo and reduces the contents over time. We have shifted from PC to SC. This study compared the outcomes of these two techniques. Methods: Records of babies with gastroschisis from 1994–2004 were reviewed. Closure type, ventilator days, days to full-feeds, hospital days, complications, and mortality were recorded. Results: Twenty-eight patients underwent PC; 20 patients had SC. Differences in ventilator days, days to full-feeds, and hospital days were not statistically significant. Nine PC patients developed closure-related complications vs. none in SC (P<0.05). Eight PC vs. two SC patients had non-closure-related complications (P<0.05). Four PC vs. zero SC patients developed necrotizing enterocolitis (P<0.05). Five PC vs. one SC patients had ventral hernia (P<0.05). No patient died. Conclusion: PC resulted in higher incidence of reclosure, non-closure-related complications, and necrotizing enterocolitis. Consequently, we recommend SC as the preferred treatment.

Focal therapy of neuroblastoma using silk films to deliver kinase and chemotherapeutic agents in vivo

Current methods for treatment of high-risk neuroblastoma patients include surgical intervention, in addition to systemic chemotherapy. However, only limited therapeutic tools are available to pediatric surgeons involved in neuroblastoma care, so the development of intraoperative treatment modalities is highly desirable. This study presents a silk film library generated for focal therapy of neuroblastoma; these films were loaded with either the chemotherapeutic agent doxorubicin or the targeted drug crizotinib. Drug release kinetics from the silk films were fine-tuned by changing the amount and physical crosslinking of silk; doxorubicin loaded films were further refined by applying a gold nanocoating. Doxorubicin-loaded, physically crosslinked silk films showed the best in vitro activity and superior in vivo activity in orthotopic neuroblastoma studies when compared to the doxorubicin-equivalent dose administered intravenously. Silk films were also suitable for delivery of the targeted drug crizotinib, as crizotinib-loaded silk films showed an extended release profile and an improved response both in vitro and in vivo when compared to freely diffusible crizotinib. These findings, when combined with prior in vivo data on silk, support a viable future for silk-based anticancer drug delivery systems.

To drain or not to drain: A single institution experience with neonatal intestinal perforation

Abstract Aims: The optimal surgical treatment for extremely-low-birth-weight (ELBW) neonates with pneumoperitoneum is controversial. This study aimed to identify clinical factors associated with two known causes of pneumoperitoneum-necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP), and assesses the treatment outcome with primary peritoneal drainage (PPD) vs. laparotomy. Methods: We reviewed and analyzed clinical characteristics and outcome from records of neonates with pneumoperitoneum treated at our institution from January 1999 to January 2003. Results: Forty-six neonates (31 NEC, 15 SIP) were treated with either PPD (20 with NEC, 13 with SIP) or laparotomy (11 with NEC, 2 with SIP). In neonates who underwent PPD, those with NEC (vs. SIP) were less likely to have a patent ductus arteriosus, but were more likely to have been fed, have drains placed later in life, have a subsequent laparotomy, a longer total parental nutrition course, a higher 30-day mortality, and to take more days to begin enteral feeds. Conclusion: The etiology of pneumoperitoneum (NEC vs. SIP) in ELBW neonates can usually be determined preoperatively. Neonates with SIP should have a drain placed while those with NEC should undergo laparotomy.

Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment.

Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multicycle chemotherapies, resulting in short‐ and long‐term toxicities. Here, we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment. The intratumoral drug concentration was significantly higher with intratumoral delivery versus IV. Furthermore, intratumor delivery decreased the maximum plasma concentration compared to IV delivery, reducing systemic exposure and possibly reduing long‐term side effects of chemotherapy exposure. Histopathologically, tumors with remission periods >25 days before recurrence transformed from a “small‐round‐blue cell” (SBRC) to predominantly “large cell” neuroblastoma (LCN) histopathology, a more aggressive tumor subtype with unfavorable clinical outcomes. These results show that intratumoral chemotherapy delivery may be a treatment strategy for pediatric neuroblastoma, potentially translatable to other focal tumors types. Furthermore, this treatment modality allows for a clinically relevant mouse model of tumor transformation that may be used for studying the phenotypical tumor recurrence and developing more effective treatment strategies for recurrent tumors.

Periodic alternating nystagmus provoked by an attack of Ménière's disease.

Periodic alternating nystagmus is a rare central nervous system disorder in which the eyes undergo a horizontal jerk nystagmus that periodically reverses direction. A patient with a hypoplastic cerebellum and enlarged cisterna magna exhibited transient periodic alternating nystagmus following an attack of Ménières disease. We hypothesize that in susceptible individuals with cerebellar disturbances, periodic alternating nystagmus may be transiently induced by vestibular stimuli.

Clinical Considerations of Focal Drug Delivery in Cancer Treatment

BACKGROUND According to the US Center for Disease Control, cancer deaths are the second most common cause of mortality in both adults and children. Definitive treatment of solid tumors involves surgical resection with or without systemic chemotherapy and radiation. The advent of local drug delivery presents a unique treatment modality that can offer substantial benefits in cancer management. Three main phases in solid tumor management exist for the treating physician: initial diagnosis with tissue biopsy, surgical resection with or without chemotherapy, and management of metastatic disease. METHODS A literature review of both basic science as well as clinical trials using local drug delivery strategies in the management of solid tumors was done on PubMed. These were then further divided into the categories of initial tissue biopsy intervention, surgical resection, and management of metastatic disease. RESULTS A total of 27 articles were review that included both pre-clinical as well as clinical investigation of local drug delivery therapies in the treatment of solid tumors. Treatments such as MRI guided therapies, FDA approved local therapies for intracranial gliomas as well as local therapy for single site metastatic disease were identified. CONCLUSION This review focuses the current state of local drug delivery in the treatment of solid tumors in both the pre-clinical as well as clinical investigation settings. Local drug delivery therapy offers an exciting new treatment modality for solid malignancies.

Transplanting a Kidney with a Renal Artery Aneurysm A Case Report and Literature Review

As a rare postoperative complication, renal artery aneurysm has been reported in 0.95% of kidney transplants. A renal artery aneurysm was repaired prior to transplantation of the kidney.

Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth

BACKGROUND Sarcoma accounts for 20% of solid tumors in children. Surgery has significant morbidity. We hypothesized that delivering chemotherapy directly into tumors through sustained release silk systems could slow tumor growth. METHODS Human Ewing sarcoma cells A673 were cultured with vincristine and doxorubicin to determine half maximal inhibitory concentration (IC50). Cells were injected into mouse hind leg to create orthotopic tumors. Tumor volumes were measured using ultrasound. When volume reached >250mm3, interventions included: implantation of drug-free silk foam (Control-F), doxorubicin 400μg foam (Dox400-F), vincristine 50μg foam (Vin50-F), drug-free silk gel (Control-G), vincristine 50μg gel (Vin50-G), or single dose intravenous vincristine 50μg (Vin50-IV). End-point was volume>1000mm3. Kaplan Meier and ANOVA were used. RESULTS IC50 for vincristine and doxorubicin was 0.5ng/mL and 200ng/mL, respectively. There was no difference between Dox400-F [6±1days to end point (DTEP)] and Control-F (5±1.3 DTEP). Vin50-F (12.4±3.5 DTEP) had slower growth compared to Control-F (p<0.001), and there was no difference between Vin50-F and Vin50-IV (14±0 DTEP). Growth was slowest with Vin50-G, 28±10.3 DTEP compared to all other treatment groups (p<0.05). CONCLUSION Sustained delivery of vincristine inside the sarcoma tumor with silk gel decreased tumor growth. Applying this intratumoral treatment strategy may potentially decrease the extent of surgical excision.