Association between Swallowing Outcomes and Dose to Critical Swallow Structures in Patients Undergoing Transoral Robotic Surgery and Post-Operative Radiation Therapy.

BACKGROUND: The radiation dose to dysphagia and aspiration-related structures (DARS) for patients undergoing transoral robotic surgery (TORS) and post-operative radiation therapy (PORT) for primary oropharyngeal carcinoma is unknown. METHODS: This prospective study measured swallowing using the MD Anderson Dysphagia Inventory at baseline and then 12-months after PORT. Dosimetric parameters were collected. RESULTS: 19 patients were recruited between 2017 and 2019. Worse swallow function at 12-months after PORT was associated with dose-parameters to the oesophageal inlet muscle, superior pharyngeal constrictor muscle and cervical oesophagus. Mean dose, V50Gy, and V60Gy to the base of tongue and pharyngeal constrictors was significantly lower in those receiving PORT to the neck alone. CONCLUSION: Dose to DARS was lower in patients who received PORT to the neck alone. In patients treated with TORS and PORT, poorer swallowing outcomes at 12 months post-treatment were associated with increased dose to oesophageal inlet muscle, superior constrictor muscle, and cervical oesophagus.

Clinicopathological Characteristics Predicting Further Recurrence and Survival Following Resection of In-Transit Melanoma Metastases.

BACKGROUND: In-transit metastases (ITMs) affect approximately 4% of patients with cutaneous melanoma. This study sought to identify clinical and pathological characteristics that predict further recurrence and survival following resection of ITMs. PATIENTS AND METHODS: Patients (n = 573) who underwent surgical resection of their first presentation of ITM following previous surgical treatment of an American Joint Committee on Cancer (AJCC) stage I-II melanoma between 1969 and 2017 were identified from an institutional database. Clinicopathological predictors of patterns of recurrence and survival following ITM resection were sought. RESULTS: The median time of ITM development was 2.4 years after primary melanoma resection. ITMs were most frequently located on the lower limb (51.0%). The most common melanoma subtype associated with ITM development was nodular melanoma (44.1%). After surgical resection of a first ITM, 65.4% of patients experienced recurrent disease. Most recurrences were locoregional (44.7%), with distant metastasis occurring in 23.9% of patients. Lower limb ITMs were more frequently associated with subsequent ITMs [odds ratio (OR) 2.41, p = 0.0002], and the lowest risk of distant metastasis (p < 0.0001) compared with other primary sites. Primary melanomas and ITM on head and neck, as well as the presence of ulceration, were associated with worse survival. CONCLUSIONS: Recurrence after surgical resection of a first ITM was common. Patterns of recurrence differed according to anatomical site; further ITM recurrences were more likely for lower limb ITMs, which were also associated with longer distant recurrence-free survival. Distant metastasis was more common for ITM on the head and neck, with worse survival.

Evidence to justify retention of transvaginal mesh: comparison between laparoscopic sacral colpopexy and transvaginal Elevate™ mesh.

INTRODUCTION AND HYPOTHESIS: To determine if laparoscopic sacral colpopexy (LSC) offers better apical support with a lower exposure rate than transvaginal mesh surgery with Elevate™. METHODS: This was a retrospective cohort study comparing patients with apical prolapse (POP-Q point C ≥ -1) who underwent Elevate™ mesh repair (n = 146) with patients who underwent laparoscopic sacral colpopexy (n = 267). RESULTS: The sacral colpopexy group had a mean age of 59 years and a BMI of 25.7. Patients in the Elevate™ group were older, with a mean age of 63 and a BMI of 26.3. Most of the patients of both groups presented with pelvic organ prolapse stage III (LSC 73.8% and Elevate™ 87.0%) and their mean POP-Q point C were not significantly different (LSC 1.4 vs Elevate™ 1.2 cm). Operative time was longer in the LSC group (113 vs 91 min, p < 0.001), but estimated blood loss was lower (75 cm3 vs 137 cm3, p < 0.001). No difference in mesh exposure rate could be found between the two groups at one year (Elevate™ 0.7% vs LSC 2.6%, OR 0.26, 95% CI 0.03 to 2.10, p = 0.21). One-year objective cure rate, defined as no descent beyond the hymen, was 97.0% in the LSC group and 96.6% in the Elevate™ group (p = .81). The overall recurrence (objective, subjective recurrence or reoperation) was also not different between the groups (LSC 4.5% vs Elevate 4.8%, p = 0.89). CONCLUSION: Transvaginal Elevate™ mesh delivers comparable apical support with a low exposure rate similar to that of laparoscopic sacral colpopexy.

The role of radiation therapy in the management of primary retroperitoneal sarcoma: A systematic review and clinical practice guidelines from the Australia and New Zealand Sarcoma Association.

While surgery is the mainstay of treatment for localised retroperitoneal sarcoma, the use of radiotherapy (RT) remains controversial. This systematic review aimed to evaluate the role of RT for retroperitoneal sarcoma. A systematic review using the population, intervention, comparison, and outcome model from 1990 to 2022 identified 66 studies (a mixture of preoperative and postoperative RT); one randomised controlled trial (RCT) with two publications, 18 registry studies, and 46 retrospective studies. In the RCT of preoperative RT, there was no difference in local/abdominal recurrence. The pooled analysis of this RCT and a retrospective study showed a significant abdominal recurrence free survival benefit with preoperative RT in low grade liposarcoma. The RCT and the majority of retrospective series found RT did not improve recurrence free survival (11 of 16 no difference in combined local and distant RFS, 11 of 13 no difference in distant metastasis free survival), disease specific survival (9 of 12 studies) or overall survival (33 of 49 studies). The majority of studies found no association between RT and perioperative morbidity. In summary, preoperative RT may improve local control for low grade (well-differentiated or grades 1-2 dedifferentiated) liposarcoma, but not other histological subtypes. There is no strong evidence that perioperative RT provides an overall survival benefit. Patients with low grade retroperitoneal liposarcoma can be considered for preoperative RT to improve abdominal recurrence free survival. The rationale and level of evidence in this scenario should be carefully discussed by the multidisciplinary team with patients. RT should not be routinely recommended for other histological subtypes.

Patterns of practice regarding use of radiation therapy following radical prostatectomy: A survey of Radiation Oncologists and Urologists in Australia and New Zealand.

INTRODUCTION: This study aimed to investigate the patterns of practices of radiation oncologists (ROs) and urologists in Australia and New Zealand with respect to the utilisation of post-prostatectomy radiation therapy (RT) and help guide the development of an update to the existing Faculty of Radiation Oncology Genito-Urinary Group post-prostatectomy guidelines. METHODS: ROs and urologists with subspecialty practice in prostate cancer from Australia and New Zealand were invited to participate in an online survey comprised of clinical scenarios regarding post-prostatectomy RT. RESULTS: Sixty-five ROs and 28 urologists responded to the survey. In the setting of low-risk biochemical relapse, the threshold for initiating RT was lower for ROs than urologists. ROs were more likely than urologists to recommend adjuvant RT for node-positive disease. When salvage RT was advised for a pT3N0R1 recurrence, there was no consensus amongst ROs on whether to add either ADT or nodal treatment over prostate bed RT alone. For a solitary PSMA-avid pelvic lymph node recurrence, whole pelvis RT with androgen deprivation therapy was the preferred treatment option (72% ROs, 43% urologists). Most ROs (92%) recommended conventionally fractionated RT to 66-70 Gy, with a boost to any PSMA PET avid recurrent disease. CONCLUSION: This survey highlights the marked discordance in practice for the management of prostate cancer relapse post-prostatectomy. This is seen not only between specialties but also within the radiation oncology community. This emphasises the need for an updated evidence-based guideline to be produced.

Surgery at specialised sarcoma centres improves patient outcomes - A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: Optimal management of sarcoma requires multidisciplinary team input throughout the process of diagnosis, treatment and follow up. This systematic review aimed to evaluate the impact of surgery performed at specialised sarcoma centres on outcomes. METHODS: A systematic review was conducted using the population, intervention, comparison and outcome (PICO) model. Medline, Embase, Cochrane Central databases were queried for publications that evaluated the local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival in patients undergoing surgery in a specialist sarcoma centre compared with non-specialist centre. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Sixty-six studies were identified. The majority of studies were Level III-3 as assessed by the NHMRC Evidence Hierarchy, whilst just over half of the studies were of good quality. Definitive surgery performed at specialised sarcoma centres was associated with improved local control as defined by lower rate of local relapse, higher rate of negative surgical margins, improved local recurrence free survival and higher limb conservation rate. Available evidences show a favourable pattern of lower 30-day and 90-day mortality rates, and greater overall survival when surgery was performed in specialist sarcoma centres compared with non-specialised centres. CONCLUSIONS: Evidences support better oncological outcomes when surgery is performed at specialised sarcoma centre. Patients with suspected sarcoma should be referred early to a specialised sarcoma centre for multidisciplinary management, which includes planned biopsy and definitive surgery.

Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Soft Tissue Sarcoma of the Extremities.

PURPOSE: Radiation therapy is a standard part of limb conserving therapy for extremity soft tissue sarcoma (STS) at high risk of recurrence. Toxic effects increase with radiation dose and volume of normal tissue irradiated. This study sought to compare dosimetry of volumetric modulated arc therapy (VMAT) with intensity modulated radiation therapy (IMRT) and to investigate the optimal planning technique. METHODS AND MATERIALS: Twenty patients with extremity STS who underwent preoperative radiation therapy (50 Gy in 25 fractions) between 2016 and 2020 at a specialised sarcoma center were included. The original treatment techniques were sliding window IMRT or 3-dimensional conformal. VMAT plans were retrospectively generated according to the original tumor and organ-at-risk constraints. Quality assurance was performed as per departmental protocol. Wilcoxon signed-rank test was used to compare dosimetric parameters (for planning target volume [PTV], in-field bone, and soft tissue structures), monitor units (MUs), and treatment time. RESULTS: Median patient age was 65 years and the majority were male (n = 14, 70%). The most common subtype was undifferentiated pleomorphic sarcoma (n = 14, 70%), and most tumors were located on the thigh (n = 12, 60%). Median PTV was 1110 cm3 and median volume of in-field bone 236 cm3. VMAT plans had significantly lower average MU (480 vs 862 MU, P < .001) and overall treatment time (300 vs 153 seconds, P < .001). PTV coverage favored VMAT, with marginally higher mean, minimum, and maximum doses and higher conformity index. However, differences were not statistically significant. Dose to infield bone and soft tissue structures were similar or slightly lower with VMAT. CONCLUSIONS: In extremity STS, VMAT plans demonstrated a favorable trend toward tumor coverage and dose conformity compared with IMRT along with significantly lower MUs and half the overall treatment time.

The benefit for radiotherapy at specialised sarcoma centres: A systematic review and clinical practice guidelines from the Australia and New Zealand Sarcoma Association.

Patients with sarcoma are best managed at specialised sarcoma centres as supported by published literature. Optimal management requires multidisciplinary team input to formulate the diagnosis and treatment sequencing taking into consideration multiple clinical and pathologic factors. This systematic review aimed to evaluate the impact on outcomes of radiotherapy at specialised sarcoma centres. A systematic review was conducted using the population, intervention, comparison and outcome model. A literature search was performed using Medline, Embase, Cochrane Central databases for publications from 1990 to February 2022 that evaluated the local control, survival and toxicity of radiotherapy at specialised sarcoma centres. A total of 21 studies were included (17 cancer registry studies, four retrospective comparative studies). Four studies reported the local recurrence endpoint when radiotherapy was part of limb conservation treatment and showed better conformity to clinical practice guidelines and an improved local recurrence free rate when radiotherapy treatment is supported through, but may not be necessarily delivered at a specialised sarcoma centres. Only one retrospective study analysed toxicity specifically and demonstrated that patients who received preoperative radiotherapy at community centres compared to radiotherapy at a specialised sarcoma centre were more likely to develop a major wound complication. Fourteen studies reported overall survival, and 12 of these showed significantly better 5-year overall survival for patients managed at specialised sarcoma centres, however the specific impact of radiotherapy delivered at sarcoma centres could not be determined. In conclusion, patients with sarcoma should be managed through specialised sarcoma centres for better oncological outcomes. Radiotherapy in specialised sarcoma centre is associated with a lower rate of wound complications and may contribute to improved oncological outcomes as part of the limb conservation treatment at a specialised sarcoma centre.

Differences in Estimates of Post-Herpetic Neuralgia Between Medical Chart Review and Self-Report.

PURPOSE: Post-herpetic neuralgia (PHN) is a common herpes zoster (HZ) complication, where pain persists 90 days after the initial HZ diagnosis. Evaluating PHN risk is essential for determining the burden on patients and health-care systems, but research shows variable estimates. The extent to which these differences are related to the assessment method has not been examined. The purpose of this study is to compare the proportion of PHN among HZ patients measured by medical chart review and self-report surveys. METHODS: PHN risk was assessed among a sample of Kaiser Permanente Southern California members with HZ. Chart reviews identified lingering pain 90-180 days post-HZ diagnosis and the Zoster Brief Pain Inventory was administered 90 days post-HZ diagnosis by telephone. Frequencies of PHN identified with each approach were cross-tabulated and stratified by sex, age group, and zoster vaccine live vaccination status. RESULTS: Chart review and self-report were largely concordant (n=875, 89.20%); however, chart review yielded lower PHN risk overall and for the stratified subgroups. PHN from self-report was substantially higher (6.30-8.33%) among patients who were male, ≥70 years, or unvaccinated. Among those who typically seek care more often (female, younger, vaccinated), the discrepancy between each method was notably lower (1.60-2.92%). CONCLUSION: Our findings suggest that chart review underestimates cases among those less likely to seek health care, including males, the elderly, and unvaccinated individuals. The agreement between the methods indicates that each can provide a reasonable approximation of PHN, but analyses should carefully control for health-care utilization.

An Unusual Case of Familial Adenomatous Polyposis Presenting with Gout and Jaundice.

We highlight an unusual case of familial adenomatous polyposis (FAP) presenting initially with gout, jaundice and a periampullary carcinoma. This case may be of interest to clinicians involved in the diagnosis and management of FAP and follow-up of patients after surgical resection.

A bacteriophytochrome regulates the synthesis of LH4 complexes in Rhodopseudomonas palustris.

The non-sulphur purple bacterium Rhodopseudomonas palustris contains five pucAB genes for peripheral light-harvesting complexes. Bacteria grown under high-light conditions absorb at 800 and 850 nm but in low-light the 850 nm peak is almost absent and LH2 complexes are replaced by LH4. The genome contains six bacteriophytochromes (Bph). Bphs sense light in the red/far-red through a reversible Pr to Pfr transformation that controls gene expression. Bph3 (RPA1537) controls the expression of a cluster of photosynthetic genes, however most of the peripheral light harvesting complex genes are outside of this region. The pucAB-d genes encode LH4 peptides and are near two Bphs (RPA3015, RPA3016). We have characterised three Bphs and show that Bph4 RPA3015 and Bph3 RPA1537 have different dark stable states. It is known that Bph3 is active in its red absorbing Pr form and suggests a working hypothesis that Bph4 is active in the Pfr state. We show that LH4 expression can be induced with red light at the Pr absorption maximum (708 nm) of Bph4. The property of light transmission of water maybe an important factor in understanding this adaptation. Bph4 can sense the reduction in light intensity indirectly through an increase in ratio of transmitted red/far-red light. The red right activated Bph4 regulates the synthesis of LH4 which concentrates bacteriochlorophyll a pigment absorption at 800 nm to exploit a recovery in water light transmission in this region.

The 7.5-A electron density and spectroscopic properties of a novel low-light B800 LH2 from Rhodopseudomonas palustris.

A novel low-light (LL) adapted light-harvesting complex II has been isolated from Rhodopseudomonas palustris. Previous work has identified a LL B800-850 complex with a heterogeneous peptide composition and reduced absorption at 850 nm. The work presented here shows the 850 nm absorption to be contamination from a high-light B800-850 complex and that the true LL light-harvesting complex II is a novel B800 complex composed of eight alpha beta(d) peptide pairs that exhibits unique absorption and circular dichroism near infrared spectra. Biochemical analysis shows there to be four bacteriochlorophyll molecules per alpha beta peptide rather than the usual three. The electron density of the complex at 7.5 A resolution shows it to be an octamer with exact 8-fold rotational symmetry. A number of bacteriochlorophyll geometries have been investigated by simulation of the circular dichroism and absorption spectra and compared, for consistency, with the electron density. Modeling of the spectra suggests that the B850 bacteriochlorophylls may be arranged in a radial direction rather than the usual tangential arrangement found in B800-850 complexes.