Elevated parathyroid hormone after parathyroidectomy delays symptom improvement

Background

Curative parathyroidectomy for primary hyperparathyroidism (PHPT) resolves various nonspecific symptoms related to the disease. Between 8% and 40% of patients with normocalcemia after parathyroidectomy have persistently elevated parathyroid hormone (ePTH) levels at follow-up. We investigated whether ePTH in the early postoperative period was associated with the timing of symptom improvement.

Materials and methods

This prospective study included adult patients with PHPT who underwent curative parathyroidectomy from November 2011 to September 2012. Biochemical testing at 2 wk postoperatively identified ePTH (defined as PTH > 72 pg/mL) versus normal PTH (nPTH). A questionnaire administered pre- and post-operatively at 6 wk and 6 mo asked patients to rate the frequency of 18 symptoms of PHPT on a five-point Likert scale. Student t-tests were used to compare pre- with postoperative changes in scores for individual symptoms.

Results

Of 194 patients who underwent parathyroidectomy, 129 (66%) participated in the study. Preoperatively, all patients were symptomatic, with a mean of 13 ± 4 symptoms. Two weeks postoperatively, 20 patients (16%) had ePTH. The percentage of patients with postoperative improvement for individual symptoms was compared between groups. At the early time point (6 wk), the ePTH group showed less improvement in 14 of 18 symptoms. This difference reached statistical significance for four symptoms: anxiety, constipation, thirst, and polyuria. By the 6-mo time point, these differences had resolved, and symptom improvement was similar between groups.

Conclusions

ePTH after curative parathyroidectomy may result in a delay in symptom improvement 6 wk postoperatively; however, this difference resolves in 6 mo.     

Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism

Background

Primary hyperparathyroidism (PHPT) is uncommon in children. The surgical management of PHPT in children has evolved over the past two decades.

Methods

A retrospective study of patients who underwent parathyroidectomy for PHPT diagnosed at age < 18 years and managed at a tertiary referral center for endocrine and familial disorders.

Results

Thirty-eight patients met eligibility criteria (1981–2012). Median age at PHPT diagnosis was 15 years. Two-thirds of patients were symptomatic (68%, n = 26), most commonly from nephrolithiasis. Twenty-six (68%) patients underwent a standard cervical exploration while 32% underwent a focused unilateral parathyroidectomy. Multiple endocrine neoplasia type 1 (MEN1) was diagnosed preoperatively in 22/26 patients. Patients with a preoperative diagnosis of MEN1 were more likely to undergo a complete initial operation (≥ 3 gland parathyroidectomy with transcervical thymectomy, 13/22, 59% vs. 0/4, 0%; P = 0.03) and less likely to have recurrent disease (10/22, 45% vs. 3/4, 75%; P < 0.001) during follow up than patients diagnosed postoperatively.

Conclusions

Children with PHPT should raise suspicion for MEN1. Preoperative MEN1 evaluation helped guide the extent of initial parathyroidectomy and was associated with lower rates of recurrence in sporadic and familial PHPT in pediatric patients. Management should occur at a high volume center with experienced clinicians and genetic counseling services.     

Primary hyperparathyroidism across the ages: presentation and outcomes

Background

Primary hyperparathyroidism (PHPT) is a disease process traditionally thought to present during middle age, but can occur at any age. The purpose of this study was to compare PHPT patient characteristics based on patient age at the time of surgical referral.

Methods

A retrospective review of a prospectively managed database of adult patients undergoing parathyroid surgery for PHPT was conducted. Patients with a negative family history, no previous parathyroid surgery, and ≥6-mo follow-up were included. Patients were grouped by age for comparison.

Results

From 2001–2012, 1372 patients met inclusion criteria. Age groups were as follows: ≤50 y, 51–60 y, 61–70 y, and >70 y. Female predominance increased with age (P > 0.01). Baseline serum parathyroid hormone levels were higher at the extremes of age (P < 0.001). Young patients had the highest serum calcium (P < 0.01), urinary calcium (P < 0.001), and T-score (P < 0.001) measures, and greater incidence of vitamin D deficiency (P = 0.03). The use of local anesthesia increased with age, whereas use of outpatient parathyroidectomy decreased with age (both P < 0.01). Rates of disease persistence (2.3%–2.9%, P = 0.95) and recurrence (2.1%–3.3%, P = 0.75) were low, and did not differ.

Conclusions

Patients at the extremes of age are referred with more elevated laboratory indices whereas those in the traditional age range have milder biochemical indices. This may result from differential surgical referral. Individuals with laboratory evidence of abnormal calcium and parathyroid hormone regulation should be evaluated for parathyroidectomy regardless of age because all ages can be successfully treated.     

Limitations of Tc99m-MIBI-SPECT Imaging Scans in Persistent Primary Hyperparathyroidism

Background  

In primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83–100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands.     

Significance of rebounding parathyroid hormone levels during parathyroidectomy

Background

Using minimally invasive parathyroidectomy (MIP), most surgeons require a 50% decline in intraoperative parathyroid hormone (IoPTH) to determine cure, but the significance of IoPTH kinetics occurring after this drop remains unknown. The aim of this study was to determine the impact of IoPTH levels that first meet criteria for cure, but then increase again, or rebound, between 10 and 15 min postexcision.

Methods

We conducted a retrospective review of patients undergoing initial parathyroidectomy for primary hyperparathyroidism at our institution from 2001 to 2011. Rebound IoPTH was defined as an increase in parathyroid hormone ≥5 pg/mL after achieving the 50% drop required for cure. Comparisons were evaluated with the Student t-test, chi-square test, or Fisher exact test where appropriate.

Results

Of the 1386 patients who met selection criteria, 86 (6.2%) patients exhibited rebound IoPTH. The mean magnitude of rebound was 13.8 ± 3.6 pg/mL. Compared with those not displaying rebound, more patients with rebound IoPTH were treated with open parathyroidectomy rather than MIP (10.8% versus 4.5%, P < 0.01). The recurrence rate among those with rebound IoPTH was more than double that of the patients without rebound IoPTH (5.8% versus 2.2%, P = 0.03). Magnitude of rebound, however, did not correlate with recurrence. The rate of persistent disease was not different between those with and without rebound IoPTH. Rebound was a much better indicator of recurrence than patients whose final IoPTH levels were not within the normal range.

Conclusions

Rebound IoPTH is more common in patients who develop recurrent hyperparathyroidism. Therefore, surgeons should closely monitor patients with rebound IoPTH for disease recurrence.     

Role of cervical ultrasound in detecting thyroid pathology in primary hyperparathyroidism

Background

Minimally invasive parathyroidectomy for primary hyperparathyroidism is made possible with accurate preoperative imaging. In addition to the detection of parathyroid adenomas, cervical ultrasound also provides concomitant assessment of the thyroid gland, and many surgeons believe that it is essential. However, the incidental identification of thyroid nodules may then subject patients to further workup and potentially invasive thyroid procedures. We sought to determine the long-term consequence of omitting preoperative ultrasound on the development of thyroid pathology and cancer.

Methods

At our institution, 222 patients with primary hyperparathyroidism underwent parathyroidectomy without preoperative cervical ultrasound from 1990–2001. Thyroid pathology discovered by follow-up after parathyroidectomy, subsequent biopsy, and surgical interventions were analyzed.

Results

Of the 222 patients who underwent parathyroidectomy, the mean age was 55 ± 1 y and 149 were female (67%). In the course of their follow-up after parathyroidectomy, 13 patients (6%) received a cervical ultrasound, and seven of 13 (3%) underwent fine needle aspiration of a thyroid nodule. Only one of seven (0.4% of all patients) was ultimately diagnosed with thyroid cancer. Four additional patients were discovered to have thyroid malignancies as a result of intraoperative decision making. All five patients are currently alive with an average follow-up time of 14.9 ± 1.6 y. No patients in this series had an unnecessary thyroid intervention.

Conclusions

In patients who underwent parathyroidectomy without a preoperative ultrasound, only a small number (0.4%) were subsequently diagnosed with thyroid cancer. Furthermore, omission of ultrasound during the localization of parathyroid glands does not have a negative impact on the diagnosis of thyroid pathology as all patients who had thyroid cancer had good outcomes, and in fact, may prevent unnecessary thyroid interventions. Therefore, the use of cervical ultrasound for parathyroid localization should be considered optional rather than essential.     

Planning of anatomical liver segmentectomy and subsegmentectomy with 3-dimensional simulation software

Background

The aim of this study was to evaluate whether 3-dimensional (3D) simulation software is applicable to and useful for anatomic liver segmentectomy and subsegmentectomy.

Methods

A prospective study of 83 consecutive patients who underwent anatomic segmentectomy or subsegmentectomy using the puncture method was performed. All patients underwent 3D simulation analysis (SA) preoperatively for planning operative procedures. The clinical information acquired by 3D SA and the consistency of virtual and real hepatectomy were evaluated.

Results

The time needed for completing 3D SA was 18.3 ± .7 minutes. Three-dimensional SA proposed resection of multiple segments or subsegments in 29 patients (35%). It also helped complement the resection line in 26 patients (31%) who lacked a bold staining area on the liver surface. The volume of segment or subsegment calculated by 3D SA was correlated with the actual resected specimen (R² = .9942, P < .01). The bordering hepatic veins were clearly exposed in 71 patients (86%), in accordance with completed drawings by 3D SA.

Conclusions

Three-dimensional SA showed accurate completed drawings and assisted liver surgeons in planning and executing anatomic segmentectomy and subsegmentectomy.     

Diabetes remission and glycemic response to pre-bariatric surgery diet

Background

Before bariatric surgery, some patients with type 2 diabetes mellitus (T2DM) experience improvement in blood glucose control and reduced insulin requirements while on a preoperative low-calorie diet (LCD). We hypothesized that patients who exhibit a significant glycemic response to this diet are more likely to experience remission of their diabetes in the postoperative period.

Materials and methods

Insulin-dependent T2DM patients undergoing bariatric surgery between August 2006 and February 2011 were eligible for inclusion. Insulin requirements at day 0 and 10 of the LCD were compared. Patients with a ≥50% reduction in total insulin dosage to maintain appropriate blood glucose control were considered rapid responders to the preoperative LCD. All others were non–rapid responders. We analyzed T2DM remission rates up to 1 y postoperatively.

Results

A total of 51 patients met inclusion criteria and 29 were categorized as rapid responders (57%). The remaining 22 were considered non–rapid responders (43%). The two groups did not differ demographically. Rapid responders had greater T2DM remission rates at 6 (44% versus 13.6%; P = 0.02) and 12 mo (72.7% versus 5.9%; P < 0.01). In patients undergoing laparoscopic gastric bypass, rapid responders showed greater excess weight loss at 3 mo (40.1% versus 28.2%; P < 0.01), 6 mo (55.2% versus 40.2%; P < 0.01), and 12 mo (67.7% versus 47.3%; P < 0.01).

Conclusions

Insulin-dependent T2DM bariatric surgery patients who display a rapid glycemic response to the preoperative LCD are more likely to experience early remission of T2DM postoperatively and greater weight loss.     

Toward eliminating catheter-associated urinary tract infections in an academic health center

Background

Eliminating catheter-associated urinary tract infections (CAUTI) is at the forefront of quality improvement and cost reduction for payers and hospitals alike. Herein we describe a double-focused strategy to eliminate CAUTI's on a surgical oncology unit over the course of 24 mo.

Methods

CAUTI's were tracked on a 30-bed surgical oncology unit 12 mo before and 12 mo after implementation of specific measures aimed at (1) decreasing utilization and (2) increasing catheter bundle and hand hygiene compliance. A policy of early Foley catheter removal was implemented. Univariate analyses were performed comparing nominal and numerical variables between the pre- and post-intervention groups.

Results

The pre- and post-intervention groups comprised of 1376 and 1467 patients, respectively. Postintervention, there was a significant decrease in both total Foley (P = 0.02) and patient (P = 0.03) days. This resulted in a significant reduction in utilization rate from 0.28 to 0.24, (P < 0.0001) and median CAUTI rate from 4.6 to 0.0 (P = 0.03). Reduced CAUTIs were associated with significant improvements in monthly bundle compliance at ≥95% (75% versus 17%, P = 0.003) and hand hygiene compliance at ≥95% (92% versus 58%, P = 0.05). Among our thoracic epidural cohort (n = 11), three patients (27%) required reinsertion for urinary retention. None of these epidural patients were diagnosed with a CAUTI.

Conclusions

Although not eliminated entirely, CAUTIs on our unit were significantly reduced through decreased utilization and improved compliance to institutional patient safety measures. Adoption of these strategies to other inpatient units would not only improve patient safety but also result in significant cost savings.     

Laterality of central venous sampling: lack of effect on the accuracy of intraoperative parathyroid hormone monitoring

Background

The purpose of this study was to determine if laterality of internal jugular vein (IJV) sampling affects the accuracy of intraoperative parathyroid hormone (PTH) monitoring during parathyroidectomy for primary hyperparathyroidism.

Methods

In this study, 109 patients underwent parathyroidectomy (82 with unilateral disease, 27 with multigland disease). PTH samples were taken from both the left and the right IJV at these time points: preincision (baseline) and then at 5, 10, and, in selected patients, 20 minutes after excision. The Miami criterion was used to determine operative success.

Results

In all 109 patients combined, the mean decreases in intraoperative PTH levels were 73.8 ± 22.2% for the left IJV and 71.9 ± 23.0% for the right IJV (P = .22). The Miami criterion was met in 105 patients: in 100 (95%) left IJV samples and 99 (94%) right IJV samples (P = 1.00).

Conclusions

No difference was found in the accuracy of intraoperative PTH monitoring between patients' left and right IJV samples. Central venous laterality did not affect fulfillment of the Miami criterion.     

Le dosage plasmatique de Neutrophil Gelatinase-Associated Lipocalin (NGAL) prédit la défaillance rénale au cours du choc septique dès l’admission en réanimation

Purpose

To validate plasma Neutrophil Gelatinase-Associated Lipocalin (pNGAL) as an early biomarker in intensive care unit (ICU) for acute kidney injury (AKI) in critically ill adult with septic shock.

Patients and method

Fifty consecutive patients with septic shock were included in this observational cohort study. AKI was defined if patients met any RIFLE or AKIN criteria. The main objective was to evaluate diagnosis value of pNGAL measured with a point-of-care device at admission (D0), at 24 hours (D1) and at 48 hours (D2).

Results

Among the 50 patients enrolled, 86% had AKI, 48% had persistent renal AKI and 30% required renal replacement therapy (RRT) during their ICU stay. At D0, pNGAL concentration was significantly higher in patients with AKI compared to patients without AKI (471 ng/mL versus 134 ng/mL, P < 0.001). This level remained significantly higher in the AKI population at D1 and D2 and pNGAL concentration at D0 among AKI patients increased with kidney failure level. At D1, pNGAL was significantly higher for persistent renal AKI rather than transient prerenal (570 ng/mL versus 337 ng/mL, P = 0.027). pNGAL concentration below 348 ng/mL at D1 was never seen in patients with RRT.

Conclusion

Plasma NGAL is a useful, sensitive and early biomarker to predict persistent AKI in septic shock at ICU admission and help to discuss RRT.     

The impact of Aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer

Background

Cancer stem cells may be associated with tumor progression and prognosis for colon cancer. We hypothesized that expression of Aldehyde dehydrogenase 1 (ALDH1) would increase with tumor progression and be associated with survival.

Methods

Tissue was obtained from resection specimens for isolation of cancer stem cells. In addition, paraffin blocks from resected colon cancers with normal colon, primary tumor, and lymph node and liver metastasis from 2000 to 2010 were identified and stained with ALDH1.

Results

In in vitro models (adherent and tumor spheres) ALHD1+ cells grew more efficiently than ALDH1− cells. ALDH1 expression was highest in peritumoral crypt cells (0.137 μm², 95% confidence interval [CI] 0.125–0.356) and normal crypts (median 0.091 μm², 95% CI 0.064–0.299) followed by lymph node metastasis (median 0.025 μm², 95% CI 0–0.131) and the primary cancers (median 0.014 μm², 95% CI 0.0123–0.154). Samples were divided into high and low ALDH1 expression. Survival was associated with expression in the primary tumor (9 versus 23 mo, P = 0.0016) expression but not peritumoral tissue (21 versus 20.5 mo, P = 0.32), normal colon (19 versus 27 mo, P = 0.289), or lymph node metastasis (23 versus 21 mo, P = 0.69). On univariate analysis, ALDH1 expression and grade were associated with survival but ages, number of lymph node metastasis, race, or grade were not associated. On multivariate analysis, only ALDH1 status continued to be associated with survival, odds ratio 4.4, and P = 0.011.

Conclusions

ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. Expression did not increase with progression from normal colon to primary tumors and metastasis.     

Retrospective Comparison of Triple-sequence Therapies in Metastatic Renal Cell Carcinoma

Background

The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined.

Objective

To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy.

Design, setting and participants

Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n = 62) or VEGFi-mTORi-rTKI (n = 41) at two German academic centers.

Intervention

Sequence of systemic targeted treatment.

Outcome measurements and statistical analysis

Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression.

Results and limitations

Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8–5.4), 4.1 mo (95% CI, 3.4–4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7–8.1) for mTORi treatment (p = 0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p = 0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4–37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4–52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases.

Conclusions

The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.     

Radioguided parathyroidectomy effective in pediatric patients

Background

Radioguided parathyroidectomy (RGP) has been shown to be effective in adult patients with hyperparathyroidism (HPT), but the utility of RGP in pediatric patients has not been systematically examined. It is not known if adult criteria for radioactive counts can accurately detect hyperfunctioning parathyroid glands in pediatric patients. The purpose of our study was to determine the utility of RGP in children with primary HPT.

Materials and methods

A retrospective review of our prospectively maintained single-institution database for patients who underwent a RGP for primary HPT identified 1694 adult and 19 pediatric patients aged 19 y or younger. From the adult population, we selected a control group matched three to one for gland weight and gender and compared pre- and postoperative laboratory values, surgical findings, pathology, and radioguidance values between the control and the pediatric groups.

Results

Excised glands from pediatric patients were smaller than those in the total adult population (437 ± 60 mg versus 718 ± 31 mg, P = 0.0004). When controlled for gland weight, ex vivo counts as a percentage of background were lower in the pediatric group (51% ± 5% versus 91% ± 11%, P = 0.04). However, ex vivo radionuclide counts >20% of the background were found in 100% of pediatric patients and 95% of the adult-matched control group.

Conclusions

All pediatric patients met the adult detection criteria for parathyroid tissue removal when a RGP was performed, and 100% cure was achieved. We conclude that RGP is a useful treatment option for pediatric patients with primary HPT.     

Does delay in appendectomy affect surgical site infection in children with appendicitis?

Purpose

The purpose of this study was to investigate the association between time from diagnosis to operation and surgical site infection (SSI) in children undergoing appendectomy.

Methods

Pediatric patients undergoing appendectomy in 2010–2012 were included. We collected data on patient demographics; length of symptoms; times of presentation, admission and surgery; antibiotic administration; operative findings; and occurrence of SSI.

Results

1388 patients were analyzed. SSI occurred in 5.1% of all patients, 1.4% of simple appendicitis (SA) patients, and 12.4% of complex appendicitis (CA) patients. SSI did not increase significantly as the length of time between ED triage and operation increased (all patients, p = 0.51; SA patients, p = 0.91; CA patients, p = 0.44) or with increased time from admission to operation (all patients, p = 0.997; SA patients, p = 0.69; CA patients, p = 0.96). However, greater length of symptoms was associated with an increased risk of SSI (p < 0.05 for all, SA and CA patients). In univariable analysis, obesity, and increased admission WBC count were each associated with significantly increased SSI. In multivariable analysis, only CA was a significant risk factor for SSI (p < 0.0001).

Conclusion

We found no significant increase in the risk of SSI related to delay in appendectomy. A future multi-institutional study is planned to confirm these results.     

Phase 1 Radioimmunotherapy Study with Lutetium 177–labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma

Background

Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed.

Objective

We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 (¹⁷⁷Lu)-girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC.

Design, setting, and participants

In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of ¹⁷⁷Lu-cG250.

Intervention

Groups of three patients received ¹⁷⁷Lu-cG250, starting at a dose level of 1110 MBq/m²¹⁷⁷Lu-cG250, with dose increments of 370 MBq/m² per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles.

Outcome measurements and statistical analysis

Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study.

Results and limitations

The MTD was 2405 MBq/m² because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ±17.0) during the last 3 mo before study entry to 5.5% (95% CI, ±5.3; p < 0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed.

Conclusions

¹⁷⁷Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m² (MTD). Radioimmunotherapy with ¹⁷⁷Lu-cG250 may stabilize previously progressive metastatic ccRCC.     

Could Interferon Still Play a Role in Metastatic Renal Cell Carcinoma? A Randomized Study of Two Schedules of Sorafenib Plus Interferon-Alpha 2a (RAPSODY)

Background

Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent.

Objective

To compare two different schedules of IFN combined with sorafenib.

Design, setting, and participants

Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0–2.

Intervention

Sorafenib 400 mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B).

Outcome measurements and statistical analysis

Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis.

Results and limitations

A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p = 0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p = 0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p = 0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3–4 toxicities were fatigue plus asthenia (28% vs 16%; p = 0.32) and hand-foot skin reactions (20% vs 18%).

Conclusions

Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC.     

Combined resection with radiofrequency ablation for bilobar hepatocellular carcinoma: a single-center experience

Background

Bilobar hepatocellular carcinoma (HCC) is not rare and curative resection often cannot be achieved. However, the long-term results of nonsurgical treatments remain unsatisfactory. This study investigates the safety, efficacy, and long-term outcome of hepatic resection (HR) and resection combined with radiofrequency ablation (RFA) in treating patients with bilobar HCC.

Materials and methods

A retrospective study of 364 patients with bilobar HCC was carried out. Among them, 89 received HR, 114 received resection combined with RFA, and 161 received transarterial chemoembolization (TACE). The clinicopathologic parameters, surgical results, long-term outcomes, and prognostic factors were analyzed.

Results

The median follow-up time was 28 mo (range, 3–84 mo). The 1-, 3-, 5-y overall survival rates were better after HR and resection combined with RFA than those of patients after TACE, that is, 78.9%, 49.4%, and 34.4%; 70.7%, 40.7%, and 22.3%; and 47.2%, 17.4%, and 8.6%, respectively (P < 0.001). Overall survival and recurrence-free survival rates were comparable between the two surgical groups. Child–Pugh stage, liver cirrhosis, and tumor number were identified as significant prognostic factors for overall survival by using the multivariate Cox model.

Conclusions

HR combined with RFA provided a chance for cure to patients with bilobar HCC who were traditionally deemed unresectable and yielded better long-term outcomes than TACE in a subset of patients. With preserved liver function, patients can receive aggressive treatment and survival could be prolonged.