Publications by authors named "Jonathan Serpell"

98 Publications

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons.

Endocr Pract 2021 Jul 12. Epub 2021 Jul 12.

Department of Epidemiology and Preventive Medicine, Monash University.

Objective: Hereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance.

Methods: A MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed.

Results: The most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening and surveillance.

Conclusion: Medical practitioners involved in the care of patients with endocrine tumors, should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of these patients and affected family members.
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http://dx.doi.org/10.1016/j.eprac.2021.07.002DOI Listing
July 2021

Patient Reported Experience on Consenting for Surgery - Elective Versus Emergency Patients.

J Surg Res 2021 Sep 23;265:114-121. Epub 2021 Apr 23.

Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia; Department of Surgery, Monash University, Melbourne, Victoria, Australia. Electronic address:

Introduction: Informed consent for surgery is a medical and legal requirement, but completing these does not necessarily translate to high patient satisfaction. This patient-reported experience study aimed to examine the surgical consent process, comparing the patients' experience in elective and emergency settings.

Methods: Over a 6-mo period, postoperative patients at The Alfred Hospital Breast and Endocrine Surgical Unit were invited to participate in a survey on the surgical consent process - including perceived priorities, information provided and overall experience. Standard statistical techniques were used, with a significant P-value of < 0.05.

Results: A total of 412 patients were invited, with 130 (32%) responses. More patients underwent elective surgery (N= 90, 69%) than emergency surgery (N = 40, 31%). Emergency patients were more likely to sign the consent form regardless of its contents (93% versus 39%, P < 0.001) and more likely to be influenced by external pressures (63% versus 1%, P < 0.001). Elective patients were more likely to want to discuss their surgery with a senior surgeon (74% versus 23%, P < 0.001) and more likely to seek advice from external sources (83% versus 10%, P < 0.001). Both groups highly valued the opportunity to ask questions (67% versus 63%, P = 0.65).

Conclusion: This study shows patients have a range of different priorities in preparation for surgery. Therefore, each consent process should be patient-specific, and focus on providing the patient with quality resources that inform decision-making.
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http://dx.doi.org/10.1016/j.jss.2021.03.026DOI Listing
September 2021

Challenges in diagnosis and management of a spiradenocarcinoma: a comprehensive literature review.

ANZ J Surg 2021 Feb 1. Epub 2021 Feb 1.

Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia.

Background: Spiradenocarcinoma is a rare skin adnexal neoplasm that may behave aggressively. It is often associated with a benign slow-growing spiradenoma that has undergone malignant transformation. Given the paucity of cases in the literature, there is a lack of consensus on treatment.

Methods: The terms 'malignant spiradenoma' or 'spiradenocarcinoma' were systematically used to search the PubMed, MEDLINE and Google Scholar databases. A total of 182 cases of spiradenocarcinoma were identified as eligible for this comprehensive literature review.

Results: Spiradenocarcinoma was commoner in older age and Caucasian race. In most cases, surgical excision for local disease is the mainstay of treatment. Lymph node dissection is usually reserved for those with suspected or confirmed lymph node metastases. High rates of local recurrence (20.8%), metastasis (37.4%) and mortality (19.1%) were identified, prompting some authors to suggest regular follow up including chest X-rays and liver function tests.

Conclusions: Patients with spiradenocarcinoma may benefit from a magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography to establish the extent of disease. We recommend wide local excision as the treatment of choice to achieve surgical margins of ≥1 cm, with node resection to be determined on a case-to-case basis. Regular follow up is important given the high rate of local recurrence, metastasis and mortality. This should include an examination of the regional lymph nodes. Further research is required to refine an evidence-based approach to spiradenocarcinoma.
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http://dx.doi.org/10.1111/ans.16626DOI Listing
February 2021

Disseminated nocardiosis with adrenal abscess masquerading as metastatic adrenal cancer in an immunocompetent adult.

ANZ J Surg 2021 06 2;91(6):E396-E398. Epub 2020 Nov 2.

Department of General Surgery, Breast and Endocrine Unit, Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.16423DOI Listing
June 2021

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

Ann Surg Oncol 2020 Dec 11;27(13):5107-5118. Epub 2020 Sep 11.

Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS).

Methods: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes.

Results: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013).

Conclusions: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.
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http://dx.doi.org/10.1245/s10434-020-09051-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674259PMC
December 2020

Investigation of recurrent laryngeal palsy rates for potential associations during thyroidectomy.

ANZ J Surg 2020 09 11;90(9):1733-1737. Epub 2020 Aug 11.

Monash University Endocrine Surgery Unit, The Alfred Hospital, Melbourne, Victoria, Australia.

Background: There are many clinical associations and potential mechanisms of injury resulting in recurrent laryngeal nerve palsy (RLNP) after thyroidectomy. One possible cause of RLNP is focal intralaryngeal compression of the recurrent laryngeal nerve (RLN), which may be associated with the tracheal tube (TT). Therefore, we examined current RLNP rates to investigate potential associations, including intralaryngeal, airway, anaesthetic and anthropometric factors.

Methods: We analysed 1003 patients undergoing thyroid surgery at The Alfred from 2010 to 2017, who had anatomically intact RLNs at the conclusion of thyroidectomy. All included patients underwent pre- and post-operative flexible nasendoscopy. The primary outcome was RLNP rate. We analysed potential associated factors including age, sex, operative time, surgical indication, pathology, American Society of Anaesthesiologists Physical Status, Mallampati scores, body mass index, intubation grade, TT size and specimen weight. The independent risk factors were identified by logistic regression analysis.

Results: Overall, RLNP occurred in 83 patients (8.3%) of which one was permanent (0.1%). On univariate analysis, RLNP was associated with male sex (P = 0.02), and duration of surgery (P = 0.002). On multivariate analysis, both male sex (P = 0.047) and duration of surgery (P = 0.04) remained significant. Further, factors postulated to cause intralaryngeal compression of the RLN, including TT size, body mass index, intubation grade and Mallampati score, were not significantly associated with RLNP.

Conclusion: Our study showed a RLNP rate of 8.3%, and associations with longer operative duration, and male sex. Potential intralaryngeal factors were not identified.
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http://dx.doi.org/10.1111/ans.16166DOI Listing
September 2020

Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study.

Eur J Surg Oncol 2020 11 13;46(11):2140-2146. Epub 2020 Jul 13.

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response.

Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres.

Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response.

Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.
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http://dx.doi.org/10.1016/j.ejso.2020.06.040DOI Listing
November 2020

Blunt abdominal trauma resulting in ovarian mucinous cystadenoma rupture.

ANZ J Surg 2021 01 8;91(1-2):197-198. Epub 2020 Jun 8.

Department of General Surgery, Breast and Endocrine Unit, Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.16045DOI Listing
January 2021

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

Ann Surg Oncol 2020 May 9;27(5):1420-1429. Epub 2020 Mar 9.

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

Background: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON).

Patients And Methods: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used.

Results: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively.

Conclusions: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.
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http://dx.doi.org/10.1245/s10434-020-08312-0DOI Listing
May 2020

How do competencies for surgery and education for life compare?

ANZ J Surg 2020 04 16;90(4):616-618. Epub 2020 Feb 16.

Carey Baptist Grammar School, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.15739DOI Listing
April 2020

Quantifying the differences in surgical management of patients with definitive and indeterminate thyroid nodule cytology.

Eur J Surg Oncol 2020 02 7;46(2):252-257. Epub 2019 Oct 7.

Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Australia; Department of Surgery, Monash University, Melbourne, Australia; Department of Surgery, Monash Health, Melbourne, Australia. Electronic address:

Introduction: Thyroid nodules are increasingly common. Despite being an essential pre-operative diagnostic tool, up to 30% of fine needle aspirate cytology (FNAC) yields a non-definitive diagnosis. This study aimed to quantify differences in surgical management of patients with definitive and indeterminate thyroid nodule cytology, and determine if clinical factors can improve cytological diagnosis.

Materials And Methods: Patients who underwent thyroidectomy for nodules from 2001 to 2015 were recruited. Those with benign and malignant preoperative cytology were included in the "definitive diagnosis" (DC) group; patients with all other preoperative cytology results were included in the "indeterminate diagnosis" (IC) group. We compared demographics and procedures between these groups. Clinical factors and demographics were also compared between patients with benign and malignant histology in the IC group.

Results: A total of 3821 cases were included. A significantly larger proportion of the IC patients had a hemithyroidectomy (IC 69% vs. DC 39%, p < 0.001) initially, and also had a significantly higher rate of two-stage surgery compared to the DC group (IC 17% vs. DC 11%, p < 0.001). Patients in the DC group were twice as likely to undergo concurrent central lymph node dissection for papillary and medullary cancers than the IC group (p < 0.001). Overall, up to 60% of IC patients had been over- or under-treated at initial surgery. The clinical factors examined were not significantly associated with higher risk of malignancy in IC patients.

Conclusion: This study highlights the potential for improved preoperative diagnosis to streamline decision making for surgical management of patients with thyroid nodules.
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http://dx.doi.org/10.1016/j.ejso.2019.10.004DOI Listing
February 2020

Changes in Tracheal Tube Cuff Pressure and Recurrent Laryngeal Nerve Conductivity During Thyroid Surgery.

World J Surg 2020 02;44(2):328-333

Endocrine Surgery Unit, Alfred Hospital, Monash University, Melbourne, Australia.

Background: The aetiology of recurrent laryngeal nerve (RLN) neurapraxia is unclear in most RLN palsies post-thyroidectomy. We hypothesised that high intralaryngeal pressures impede RLN conductivity, in turn contributing to RLN palsy. Therefore, we measured tracheal tube (TT) cuff pressure (as a surrogate for intralaryngeal pressure) and RLN conduction during ten standard manoeuvres in thyroidectomy, to assess for correlation between cuff pressure and RLN conductivity.

Methods: A prospective cohort study of thyroidectomy during 2018. For each thyroid lobe, TT cuff pressure was continuously measured via an air pressure transducer. RLN conduction (amplitude and latency) was measured using continuous neuromonitoring. Changes in mean TT cuff pressure and median nerve conduction from baseline measurements were analysed using Student's t test and Wilcoxon signed-rank test.

Results: In a total of 50 RLNs, the mean baseline TT cuff pressure of 19.5 ± 8.9 mmHg increased significantly to 22.0 mmHg during anteromedial rotation of the thyroid (p < 0.05). RLN conduction changed during manipulation of the superior thyroid pole with shortening of latency (-0.49% from baseline, p = 0.05) and reduction in amplitude (-12.0% from baseline, p = 0.02). The timing of these deviations did not correlate with the increased TT cuff pressure. In three cases of temporary RLN palsy, the mean cumulative case TT cuff pressure was significantly higher (24.8 mmHg, p = 0.02).

Conclusions: This study demonstrates that TT cuff pressure and RLN conductivity can change significantly with manipulation of the thyroid and that high TT cuff pressures may be associated with RLN injuries.
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http://dx.doi.org/10.1007/s00268-019-05185-7DOI Listing
February 2020

Anti-Thyroid Antibodies and TSH as Potential Markers of Thyroid Carcinoma and Aggressive Behavior in Patients with Indeterminate Fine-Needle Aspiration Cytology.

World J Surg 2020 02;44(2):363-370

Department of General Surgery, Monash University Endocrine Surgery Unit, The Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Background: Indeterminate fine-needle aspiration cytology (FNAC) imposes challenges in the management of thyroid nodules. This study aimed to examine whether preoperative anti-thyroid antibodies (Abs) and TSH are indicators of thyroid malignancy and aggressive behavior in patients with indeterminate FNAC.

Methods: This was a retrospective study of thyroidectomy patients from 2008 to 2016. We analyzed Abs and TSH levels, FNAC, and histopathology. Serum antibody levels were categorized as 'Undetectable', 'In-range' if detectable but within normal range, and 'Elevated' if above upper limit of normal. 'Detectable' levels referred to 'In-range' and 'Elevated' combined.

Results: There were 531 patients included. Of 402 patients with preoperative FNAC, 104 (25.9%) had indeterminate cytology (Bethesda III-V). Of these, 39 (37.5%) were malignant and 65 (62.5%) benign on histopathology. In the setting of indeterminate FNAC, an increased risk of malignancy was associated with 'Elevated' thyroglobulin antibodies (TgAb) (OR 7.25, 95% CI 1.13-77.15, P = 0.01) and 'Elevated' thyroid peroxidase antibodies (TPOAb) (OR 6.79, 95% CI 1.23-45.88, P = 0.008). Similarly, while still 'In-range', TSH ≥ 1 mIU/L was associated with an increased risk of malignancy (OR 3.23, 95% CI 1.14-9.33, P = 0.01). In all patients with malignancy, the mean tumor size was 8 mm larger in those with TSH ≥ 1 mIU/L (P = 0.03); furthermore, in PTC patients, 'Detectable' TgAb conferred a 4 × risk of lymph node metastasis (95% CI 1.03-13.77, P = 0.02).

Conclusion: In this cohort, in indeterminate FNAC patients, Abs and TSH were associated with an increased risk of malignancy. Additionally, TgAb and TSH were potential markers of aggressive biology. As such, they may be diagnostic and prognostic adjuncts.
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http://dx.doi.org/10.1007/s00268-019-05153-1DOI Listing
February 2020

Routine Preoperative Laryngoscopy for Thyroid Surgery Is Not Necessary Without Risk Factors.

Thyroid 2019 11 29;29(11):1646-1652. Epub 2019 Aug 29.

Department of General Surgery, Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Australia.

Routine preoperative vocal cord (VC) assessment with laryngoscopy in patients undergoing thyroidectomy allows clear documentation of baseline VC function, aids in surgical planning in patients with palsies, and facilitates interpretation of intraoperative neuromonitoring (IONM) findings. We aimed to determine the incidence of preoperative vocal cord palsy (VCP); to evaluate the associated risk factors for preoperative VCP; and to calculate the cost-savings potential of implementing a selective approach. Patients with a pre-thyroidectomy VC assessment by fiberoptic laryngoscopy were retrospectively recruited from the Monash University Endocrine Surgery Unit database from 2000 to 2018. Cases with preoperative VCP were reviewed for potential contributing factors and compared with a non-palsy cohort. Of the 5987 patients who had preoperative laryngoscopy, VCP was documented in 41 (0.68%) patients. Four clinical parameters were found to be potential indicators of VCP, including: age ( < 0.001), nodule ≥3.5 cm recorded on ultrasound imaging ( = 0.01), presence of voice symptoms ( < 0.001), and previous neck surgery ( < 0.001). Malignant cytology ( = 0.5) and exposure to head and neck irradiation were not different between the groups. Utilizing these risk factors, 2354 (39%) patients had at least one feature that may raise suspicion for preoperative VCP. By performing preoperative laryngoscopy only on this subset of patients, the potential cost savings exceeds 400 Australian Dollars per patient. Using this large dataset, we have established that a VCP is rare in the absence of a large nodule, hoarseness, or previous neck surgery. Therefore, in the era of IONM, we support a selective approach to preoperative laryngoscopy by using the aforementioned criteria.
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http://dx.doi.org/10.1089/thy.2019.0145DOI Listing
November 2019

Long-Term Oncologic Outcomes After Isolated Limb Infusion for Locoregionally Metastatic Melanoma: An International Multicenter Analysis.

Ann Surg Oncol 2019 Aug 25;26(8):2486-2494. Epub 2019 Mar 25.

Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma.

Methods: Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer [AJCC] 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS).

Results: A total of 687 first-time ILIs were performed (stage 3B: n = 383, 56%; stage 3C; n = 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response [CR], 28.9%; partial response [PR], 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months; p < 0.0001), DPFS (53.6 vs 12.7 months; p < 0.0001), and OS (46.5 vs 24.4 months; p < 0.0001) than the nonresponders (SD + PD).

Conclusion: This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.
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http://dx.doi.org/10.1245/s10434-019-07288-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771312PMC
August 2019

Evaluation of the efficacy and toxicity of upper extremity isolated limb infusion chemotherapy for melanoma: An Australian multi-center study.

Eur J Surg Oncol 2019 05 27;45(5):832-837. Epub 2019 Feb 27.

Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Discipline of Surgery, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address:

Background: Isolated limb infusion (ILI) is a minimally invasive treatment for patients with locally advanced extremity melanoma. Most studies combine results of upper-limb ILI (UL-ILI) and lower-limb ILI (LL-ILI), leaving UL-ILIs relatively underreported as LL-ILIs comprise the vast majority in these reports. However, differences between the two procedures may be clinically important. The aim of this study was to evaluate the efficacy and toxicity of UL-ILI in an Australian multi-center setting.

Patients And Methods: 316 ILI procedures for melanoma performed between 1992 and 2008 in five Australian institutions were analyzed. In all institutions melphalan (±actinomycin D) was circulated in the isolated limb for 20-30 min.

Results: Baseline patient characteristics for UL-ILI (n = 27) and LL-ILI (n = 289) were similar, except that more men underwent UL-ILI (66% vs. 38%; p = 0.007) and disease in LL-ILI was mostly located on the distal limb (p = 0.02). Median tourniquet times were shorter for UL-ILI (38 vs. 48 min; p = 0.04) and UL-ILI patients experienced less limb toxicity (Grade III/IV in 24% vs. 31%; p = 0.01). Complete response (CR) rates were similar: 33% after LL-ILI (p = 0.70), 30% after UL-ILI, while overall response (OR) rates were higher after LL-ILI: (76%) than UL-ILI (59%; p = 0.05). No difference in survival was seen.

Conclusions: UL-ILI is safe to perform and effective, resulting in low limb toxicity. CR rates were similar to those for LL-ILI, but OR rates were lower for UL-ILI. It may be possible to improve OR rates achieved by UL-ILI by optimizing perioperative factors, while maintaining low toxicity.
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http://dx.doi.org/10.1016/j.ejso.2019.02.026DOI Listing
May 2019

Development of a binational thyroid cancer clinical quality registry: a protocol paper.

BMJ Open 2019 01 28;9(1):e023723. Epub 2019 Jan 28.

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Introduction: The occurrence of thyroid cancer is increasing throughout the developed world and since the 1990s has become the fastest increasing malignancy. In 2014, a total of 2693 Australians and 302 New Zealanders were diagnosed with thyroid cancer, with this number projected to rise to 3650 in 2018. The purpose of this protocol is to establish a binational population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand.

Methods And Analysis: The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) aims to capture clinical data for all patients over the age of 16 years with thyroid cancer, confirmed by histopathology report, who have been diagnosed, assessed or treated at a contributing hospital. A multidisciplinary steering committee was formed which, with operational support from Monash University, established the ANZTCR in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 20 sites expected to come on board across Australia in 2018. A modified Delphi process was undertaken to determine the clinical quality indicators to be reported by the registry, and a minimum data set was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery and 90-day follow-up.

Future Plans: The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand current practice in the treatment of thyroid cancer and identify variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer term outcome data particularly for patients with poor prognostic disease will add significant further value to the registry.
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http://dx.doi.org/10.1136/bmjopen-2018-023723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352782PMC
January 2019

Thyroidectomy Then and Now: A 50-Year Australian Perspective.

World J Surg 2019 Apr;43(4):1022-1028

Department of General Surgery, Monash University Endocrine Surgery Unit, The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC, 3004, Australia.

Background: Since the mid-1800s, thyroidectomy has transformed from a procedure associated with high to near-zero mortality. Nonetheless, surgeons must continue to strive to improve patient care. Using historical records and contemporary data, this study compares the practice and outcomes of thyroid surgery at a tertiary institution during two periods, 50 years apart.

Methods: 'The Alfred Hospital Clinical Reports' recorded all cases of surgically managed thyroid disease from 1946 to 1959. These historical cases were compared to contemporary thyroidectomy cases at the Alfred Hospital from 2007 to 2016. Cases were compared for surgical indication and post-operative outcomes.

Results: There were 746 patients in the historical group (mean age 53 years; 87% female) and 787 patients in the contemporary group (mean age 52 years; 80% female). The most common indication for thyroidectomy in both groups was non-toxic nodular goitre. A greater proportion of the contemporary group were diagnosed with thyroid malignancy (27% vs. 8%; p < 0.001). The contemporary group recorded significantly fewer cases of thyrotoxic crisis (2.1% vs. 0%; p = 0.001), permanent nerve palsy (4.6% vs. 0.4%; p < 0.001) and bilateral nerve palsy (1.2% vs. 0%; p = 0.01). There were no mortalities in the contemporary group, while the historical data recorded three deaths (0.44%).

Conclusions: This study compared thyroid surgery in two cohorts separated by a 50-year period. While it is not surprising that outcomes of thyroidectomy have improved, this study uniquely demonstrates trends of thyroid surgery over time and areas in which further improvements may be made.
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http://dx.doi.org/10.1007/s00268-018-04885-wDOI Listing
April 2019

International neuromonitoring study group guidelines 2018: Part II: Optimal recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of surgical, laryngeal, and neural electrophysiologic data.

Laryngoscope 2018 10 6;128 Suppl 3:S18-S27. Epub 2018 Oct 6.

Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, U.S.A.

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.
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http://dx.doi.org/10.1002/lary.27360DOI Listing
October 2018

International neural monitoring study group guideline 2018 part I: Staging bilateral thyroid surgery with monitoring loss of signal.

Laryngoscope 2018 10 5;128 Suppl 3:S1-S17. Epub 2018 Oct 5.

Mount Sinai Hospital, Department of Otolaryngology, Toronto, Ontario, Canada.

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.
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http://dx.doi.org/10.1002/lary.27359DOI Listing
October 2018

Adrenal incidentaloma follow-up is influenced by patient, radiologic, and medical provider factors: A review of 804 cases.

Surgery 2018 12 28;164(6):1360-1365. Epub 2018 Aug 28.

Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia; Department of Surgery, Monash University, Melbourne, Victoria, Australia.

Background: The majority of adrenal incidentalomas are benign, although some are large, functional, or malignant and may require surgery. Therefore all require follow-up. This study aimed to determine the pattern of adrenal incidentaloma follow-up in a level 1 trauma center, focusing on the factors that influence whether follow-up is facilitated.

Methods: Patients with computed tomography-detected adrenal incidentalomas between January 2010 and September 2015 were included. A keyword search identified case files, which were reviewed for demographic characteristics, managing unit, computed tomography indication and findings, and follow-up arrangements. Statistical analysis was performed using Stata SE Version 14.

Results: A total of 38,848 chest and abdominal computed tomographic scans were performed in the study period, revealing 804 patients with adrenal incidentalomas who met inclusion criteria (mean age 65, 58% male). The mean size of adrenal incidentaloma was 23 mm. Follow-up was organized in 30% of cases and was more likely to occur in younger patients (mean age 62 vs 66, P < .001); in larger lesions (mean size 26 mm vs 21 mm, P < .001); if the computed tomographic scan suggested follow-up (P < .001); or if the computed tomography report suggested a diagnosis (P < .001). Follow-up arrangements were most likely to be made by the trauma unit (39%, P = .01).

Conclusion: This study highlights that adrenal incidentalomas follow-up is often overlooked, and that follow-up is influenced by patient, radiologic, and medical provider factors. An adrenal lesion follow-up protocol may improve follow-up rates but requires further analysis.
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http://dx.doi.org/10.1016/j.surg.2018.07.011DOI Listing
December 2018

Response to Re: Body weight change is unpredictable after total thyroidectomy.

ANZ J Surg 2018 06;88(6):655-656

Monash University Endocrine Surgery Unit, The Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.14686DOI Listing
June 2018

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

N Engl J Med 2018 Jun 9;378(24):2263-2274. Epub 2018 May 9.

From Alfred Hospital (P.S.M., J.S., S.W.), Monash University (P.S.M., R.B., T.C., A.F., K.L., J.S., S.W.), and the University of Melbourne (R.B., P.P., D.S., C.C., K.L.), Melbourne, VIC, Austin Hospital, Heidelberg, VIC (R.B., P.P., D.S., C.C.), Royal Perth Hospital and the University of Western Australia, Perth (T.C.), Royal Melbourne Hospital, Parkville, VIC (K.L.), and Royal Adelaide Hospital and Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA (T.P.) - all in Australia; Auckland City Hospital, Auckland, and the Medical Research Institute of New Zealand, Wellington - both in New Zealand (S. McGuinness, R.P.); the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); University Health Network, Toronto (S. McCluskey); and Derriford Hospital, Plymouth, United Kingdom (G.M.).

Background: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion.

Methods: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

Results: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.

Conclusions: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).
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http://dx.doi.org/10.1056/NEJMoa1801601DOI Listing
June 2018

Preventing hypoparathyroidism after total thyroidectomy.

ANZ J Surg 2018 03;88(3):127-128

Specialist Centre, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.14235DOI Listing
March 2018

Surgical management of the recurrent laryngeal nerve in thyroidectomy: American Head and Neck Society Consensus Statement.

Head Neck 2018 04 20;40(4):663-675. Epub 2018 Feb 20.

Division of Thyroid and Parathyroid Surgery, Department of Otolaryngology Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

"I have noticed in operations of this kind, which I have seen performed by others upon the living, and in a number of excisions, which I have myself performed on the dead body, that most of the difficulty in the separation of the tumor has occurred in the region of these ligaments…. This difficulty, I believe, to be a very frequent source of that accident, which so commonly occurs in removal of goiter, I mean division of the recurrent laryngeal nerve." Sir James Berry (1887).
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http://dx.doi.org/10.1002/hed.24928DOI Listing
April 2018

Body weight change is unpredictable after total thyroidectomy.

ANZ J Surg 2018 Mar 14;88(3):162-166. Epub 2018 Feb 14.

Monash University Endocrine Surgery Unit, The Alfred Hospital, Melbourne, Victoria, Australia.

Background: There is a common perception that total thyroidectomy causes weight gain beyond expected age-related changes, even when thyroid replacement therapy induces a euthyroid state. The aim of this study was to determine whether patients who underwent total thyroidectomy for a wide spectrum of conditions experienced weight gain following surgery.

Methods: We retrospectively studied 107 consecutive total thyroidectomy patients treated between January 2013 and June 2014. Medical records were reviewed to determine underlying pathology, thyroid status, use of antithyroid drugs and preoperative weight. Follow-up data were obtained from 79 patients at least 10 months post-operatively to determine current weight, the type of clinician managing thyroid replacement therapy and patient satisfaction with post-thyroidectomy management.

Results: The cohort was 73% female, with a mean age of 55.8 ± 15.7 years and a mean preoperative weight of 78.8 ± 17.5 kg. Commonest pathologies were multinodular goitre, Graves' disease, thyroid cancer and Hashimoto's thyroiditis. Preoperatively, 63.2% of patients were hyperthyroid. Mean weight change at follow-up was a non-significant increase of 0.06 ± 6.9 kg (P = 0.094). Weight change was not significant regardless of preoperative thyroid function status. This study did not demonstrate any significant differences in clinical characteristics (including post-operative thyroid-stimulating hormone) between the group with >2% weight gain and those who did not.

Conclusions: This study did not reveal significant weight gain following thyroidectomy for a wide spectrum of pathologies. Specifically, preoperative hyperthyroidism, female gender and use of antithyroid medications do not predict weight gain after thyroid surgery.
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http://dx.doi.org/10.1111/ans.14421DOI Listing
March 2018

Safety and Efficacy of Isolated Limb Infusion Chemotherapy for Advanced Locoregional Melanoma in Elderly Patients: An Australian Multicenter Study.

Ann Surg Oncol 2017 Oct 10;24(11):3245-3251. Epub 2017 Aug 10.

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

Background: Isolated limb infusion (ILI) offers a minimally invasive treatment option for locally advanced extremity melanoma.

Objective: The aim of the current study was to evaluate the safety and efficacy of ILI in elderly patients in an Australian multicenter setting.

Methods: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were identified and analyzed, with the main focus on elderly patients (≥75 years of age). All institutions used the same protocol: melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D), and toxicity, responses, and survival were recorded.

Results: Characteristics of patients aged ≥75 years (n = 148) were similar to those aged <75 years (n = 168), except that older patients had more melanoma deposits (median 4 vs. 5; p = 0.035) and lower limb volumes (5.4 vs. 6.5 L; p = 0.001). Median drug circulation times were lower in the older group (21 vs. 24 min; p = 0.04), and older patients experienced less limb toxicity (grade III/IV in 22 and 37% of patients, respectively; p = 0.003). A complete response (CR) was seen in 27% of patients aged ≥75 years and in 38% of patients aged <75 years (p = 0.06), while overall response rates were 72 and 77%, respectively (p = 0.30). No difference in survival was seen (p = 0.69).

Conclusions: The ILI technique proved safe and effective in elderly patients. When present, toxicity was localized, and lower compared with younger patients, possibly due to shorter drug circulation times. CR rates were higher in younger patients, although not significantly, while overall response and survival were equal. Optimization of perioperative factors in elderly patients may allow response rates to be raised further, while maintaining low toxicity.
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http://dx.doi.org/10.1245/s10434-017-6046-5DOI Listing
October 2017

A case of an incidental primary adrenal lymphoma in a patient with newly diagnosed human immunodeficiency virus.

ANZ J Surg 2019 03 23;89(3):E106-E108. Epub 2017 Jun 23.

Department of General Surgery, The Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.14078DOI Listing
March 2019

Response to the letter to the editor regarding "Quantitative study of voice dysfunction after thyroidectomy".

Surgery 2017 09 13;162(3):692-693. Epub 2017 May 13.

Alfred Hospital, General Surgery, Prahran, Australia.

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http://dx.doi.org/10.1016/j.surg.2017.03.022DOI Listing
September 2017
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