Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral.

The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.

Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer.

BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2 mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0-13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17-0.80, p = 0.008)-CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.

The use of combined radial forearm cutaneous and radial forearm fascial flaps in head and neck reconstruction: a case series.

INTRODUCTION: Reconstruction of complex head and neck cases involving bony and dural defects poses many issues. The primary aims of reconstruction are to provide a tight dural seal with good cranial support while also achieving a satisfactory cosmetic result. AIMS: This study describes the use of combined radial forearm cutaneous flap and radial forearm fascial flaps for reconstruction of complex skull defects where each component is used for a distinct reconstructive purpose. The benefits of this technique are illustrated in the cases of three patients requiring reconstruction following tumor resection. METHODS: The fascial component was used as a seal for dural defects. The cutaneous flap was then used to reconstruct the concomitant cutaneous defect. CONCLUSION: The combined use of the fascial and cutaneous components of the radial forearm flap, where each is used for a distinct reconstructive purpose, increased the reconstructive versatility of this commonly used flap. The fascial flap was a thin, pliable, and highly vascularized piece of tissue that was effectively used to provide a watertight seal for the dural defect. The simultaneous use of the cutaneous flap gave support to the bony defect while providing a good cosmetic result.

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial.

BACKGROUND: Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes the long-term follow-up of a large European multicenter trial evaluating the accuracy of the technique. METHODS: A total of 227 SNB procedures were carried out across 6 centers, of which 134 were performed in clinically T1/2 N0 patients. All patients underwent SNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with hematoxylin and eosin (H&E) staining, step-serial sectioning (SSS), and immunohistochemistry (IHC). There were 79 patients who underwent SNB as the sole staging tool, while 55 patients underwent SNB-assisted elective neck dissection. RESULTS: Sentinel nodes were successfully identified in 125 of 134 patients (93%), with a lower success rate observed for floor-of-mouth tumors (FoM; 88% vs. 96%, P = 0.138). Also, 42 patients were upstaged (34%); of these, 10 patients harbored only micrometastatic disease. At a minimum follow-up of 5 years, the overall sensitivity of SNB was 91%. The sensitivity and negative predictive values (NPV) were lower for patients with FoM tumors compared with other sites (80% vs. 97% and 88% vs. 98%, respectively, P = 0.034). CONCLUSIONS: Sentinel node biopsy is a reliable and reproducible means of staging the clinically N0 neck for patients with cT1/T2 HNSCC. It can be used as the sole staging tool for the majority of these patients, but cannot currently be recommended for patients with tumors in the floor of the mouth.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma.

The appearance of lymph node metastases represents the most important adverse prognostic factor in head and neck squamous cell carcinoma. Therefore, accurate staging of the cervical nodes is crucial in these patients. The management of the clinically and radiologically negative neck in patients with early oral and oropharyngeal squamous cell carcinoma is still controversial, though most centers favor elective neck dissection for staging of the neck and removal of occult disease. As only approximately 30% of patients harbor occult disease in the neck, most of the patients have to undergo elective neck dissection with no benefit. The sentinel node biopsy concept has been adopted from the treatment of melanoma and breast cancer to early oral and oropharyngeal squamous cell carcinoma during the last decade with great success. Multiple validation studies in the context of elective neck dissections revealed sentinel node detection rates above 95% and negative predictive values for negative sentinel nodes of 95%. Sentinel node biopsy has proven its ability to select patients with occult lymphatic disease for elective neck dissection, and to spare the costs and morbidity to patients with negative necks. Many centers meanwhile have abandoned routine elective neck dissection and entered in observational trials. These trials so far were able to confirm the high accuracy of the validation trials with less than 5% of the patients with negative sentinel nodes developing lymph node metastases during observation. In conclusion, sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma can be considered as safe and accurate, with success rates in controlling the neck comparable to elective neck dissection. This concept has the potential to become the new standard of care in the near future.

Does tumor depth affect nodal upstaging in squamous cell carcinoma of the head and neck?

PURPOSE: The aim of this study was to determine whether tumor depth affects upstaging of the clinically node-negative neck, as determined by sentinel lymph node biopsy with full pathologic evaluation of harvested nodes including step-serial sectioning (SSS) and immunohistochemistry (IHC). PATIENTS AND METHODS: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin-eosin staining, SSS, and IHC. Patients upstaged by SSS/IHC were denoted pN1mi. RESULTS: One hundred one of 172 patients were staged pN0, with 71 (41%) patients upstaged. Increasing tumor depth was associated with higher likelihood of upstaging (P < .001). Tumor depth showed a positive correlation with nodal stage according to TNM classification (P < .001). Tumor depth greater than 4 mm appears to be the most appropriate cutoff for risk stratification, although tumors in the oropharynx may require a lower value. CONCLUSION: Tumor depth is an important prognostic factor for patients with SCC of the oral cavity or oropharynx. Tumors greater than 4 mm are associated with greater risk of upstaging; however, this optimum cutoff value may vary between primary tumor sites.

Which venous system to choose for anastomosis in head and neck reconstructions?

It has been postulated that venous thrombosis in free flap surgery necessitates the use of 2 venous anastomoses into different venous systems. We retrospectively analyzed a single surgeon's 10-year experience (August 1993 to August 2003) in primary free flap reconstruction for malignant tumors of the head and neck. Of 492 primary reconstructions that did not need a vein graft, vein loop, or cephalic turnover procedure, 251 used the internal jugular venous system as venous outflow, 140 used the subclavian system as outflow, and 101 used both. Two hundred thirty-eight of 251 (95%) of flaps utilizing the internal jugular venous system for outflow were successful compared with 129 of 140 (92%) of flaps utilizing the subclavian system. Where both venous systems were used the success rate was 101 of 101 (100%) (P < 0.05). Where possible, a second venous anastomosis should be performed utilizing both venous drainage systems.

One stage mastopexy augmentation in the ptotic patient. The superiorly based dermal flap for autologous reinforcement of the inferior pole.

BACKGROUND: The use of one stage mastopexy augmentation in the ptotic patient remains controversial. Expansion of breast volume and reduction of the skin envelope contradict each other and increase the risks of potential complications. By carefully selecting and consenting patients appropriately I describe the use of the superiorly based dermal flap for autologous reinforcement of the inferior pole to increase safety and reliability in one stage mastopexy augmentation. OBJECTIVES: To determine whether the superiorly based dermal flap could provide a safe and reliable method of one stage mastopexy augmentation. METHODS: 40 one staged mastopexy augmentation procedures were performed on 21 patients. Patients were excluded if they smoked, BMI >30, had significant co-morbidities, had unrealistic expectations, required a nipple lift of >8 cm, wanted >400cc volume in primary cases or >25% increase in volume in secondary mastopexy augmentation. Both round and anatomical implants were used in either the sub glandular or dual plane pocket depending on patient's aesthetic wishes. RESULTS: The average implant size was 290cc and average nipple lift was 5 cm. After an average follow up of 27months there have been no implant based complications, no reoperations and no infections/haematomas/seromas. CONCLUSIONS: Careful selection and consent of patients make the use of the superiorly based dermal flap for autologous reinforcement of the inferior pole a safe reliable technique in one stage mastopexy augmentation.

The nomenclature of groin dissection for melanoma - Time to simplify.

INTRODUCTION: A wide variety of terms are used to describe different extents of groin dissection for stage 3 melanoma which may result in confusion and reduce effectiveness of research. We aim to evaluate the published terminology. METHODS: A PubMed review was conducted using the terms 'melanoma' plus 'inguinal'; 'groin'; 'pelvic'; 'ilioinguinal' dissection. 63 papers were included from 1956 to March 2015. A review of anatomy and coding was also conducted. RESULTS: Inguinal dissection was described using 8 terms from 56 papers with 7 papers using multiple terms for the same procedure. 'Superficial dissection' was the most common term despite inguinal-nodal tissue being separated into superficial and deep layers anatomically. ICD10PCS and OPSC code for 'inguinal' with no anatomical definition, CPT codes for 'inguinofemoral/superficial'. Combination inguino-pelvic dissection was described using 11 terms from 51 papers with 15 papers using multiple terms for the same procedure. 'Ilioinguinal' and 'Deep' were the most common despite most pelvic dissections including obturator nodes. ICD10PCS and OPSC code for 'pelvic' with no anatomical definition and CPT codes for 'superficial plus pelvic'. CONCLUSION: Many different terms are used to describe the same procedures, often within the same article. The lack of clarity can confuse readers, hinder comparative research and jeopardise patient care. Imprecise documentation of anatomical definition limits surgical outcome reporting and can impede planning for revision surgery. Standardisation is necessary and groin dissection should be defined by anatomical boundaries e.g. 'superficial' and 'deep' inguinal; 'pelvic'; 'inguino-pelvic' with clear documentation of extent.

Biochemical markers for post-operative fatigue after major surgery.

OBJECTIVE: To establish a link between tryptophan (a precursor for 5-hydroxytryptamine (5-HT) or serotonin, involved in sleep and fatigue) and post-operative fatigue after major surgery. BACKGROUND: There is a link between tryptophan (the precursor for the neurotransmitter 5-hydroxytryptamine), and its competitive binding with non-esterified fatty acids (NEFA) to albumin in the blood. An increase in the plasma concentration of free tryptophan can lead to an increased rate of synthesis of 5-HT in the brain. Free tryptophan competes with the branched chain amino acids (BCAA) for the same port of entry across the blood-brain barrier. It is suggested that the plasma concentration of these amino acids could be a marker of post-operative fatigue. In a previous study undertaken in this laboratory on patients undergoing two different types of major surgery, similar post-operative increases were observed in the plasma concentration of free tryptophan and the plasma concentration ratio of free tryptophan to branched chain amino acids. However, the study was retrospective and no measure of fatigue had been made. METHODS: In the present study, this deficiency has been addressed by administering a modified Profile of Mood States questionnaire to patients undergoing reconstructive or colorectal surgery. In addition, blood samples were measured for plasma free tryptophan, albumin, NEFA and branched chain amino acids before and on 2 days after surgery. RESULTS: There was a significant correlation between fatigue scores and plasma free tryptophan (P<0.000), and the plasma concentration ratio of free tryptophan/BCAA (P<0.016) after surgery in all the patients studied (n=34). This correlation was more marked in the colorectal-surgery patients, in whom surgery was more severe. In the three categories of patients receiving elective reconstructive surgery (n=24), those having breast reductions (n=6) had a lower plasma concentration of NEFA and appeared to recover from fatigue more quickly than those with pre-tibial lacerations or malignant melanoma. CONCLUSIONS: These data provide further evidence of a possible biochemical mechanism for central fatigue which involves a precursor of 5-HT. The provision of branched chain amino acids may help to combat the surge in free tryptophan that occurs during stress such as major surgery.

Is superficial inguinal node dissection adequate for regional control of malignant melanoma in patients with N1 disease?

INTRODUCTION: The optimum extent of surgery for inguinal nodal metastases due to melanoma remains controversial. Recent evidence suggests a conservative superficial groin dissection (SGD) may provide adequate regional control. AIM: To evaluate patients with N1 stage disease treated with SGD to determine the recurrence rates and to evaluate whether SGD was adequate for regional control in these patients. MATERIALS AND METHODS: Patients undergoing SGD between April 2005 and April 2012 were retrospectively analysed from a prospectively collected database. RESULTS: Sixty patients were treated by SGD of which 40 had palpable disease and 20 had a positive sentinel node. Overall median follow-up was 38 months, with median follow-up for the SNB group being 29 months and that of the PD group 49 months. Three patients (5%) developed groin recurrence following SGD. All patients recurred within the superficial site of surgery; there was no deep inguinal or pelvic recurrence. Distant recurrence occurred in 22 patients (36.7%), with 21 of these patients coming from the PD group and one from the SNB group. This difference was statistically significant (p < 0.05). Overall survival at 5 years was 70.3%. Survival at 5 years in the PD group was 63.8% and in the SNB group it was 90.9%, this difference was approaching significance (p = 0.08). CONCLUSION: SGD appears adequate for local disease control in patients with N1 sentinel node positive disease. Longer term followup for N1 palpable disease is required to determine the suitability of SGD for this group of patients.

Variations in the anatomy of the posterior auricular nerve and its potential as a landmark for identification of the facial nerve trunk: a cadaveric study.

The posterior auricular nerve (PAN) is the first extracranial branch of the facial nerve trunk. It innervates the posterior belly of the occipitofrontalis and the auricular muscles and contributes cutaneous sensation from the skin covering the mastoid process and parts of the auricle. This study was carried out to provide a detailed account of its anatomy and to ascertain its reliability as a surgical landmark for the facial nerve. Eleven facial sides from six formalin-fixed cadavers were dissected. The course and arborisation pattern of the PAN was observed, and its position of emergence from the facial nerve trunk (FNT) was measured. The PAN arose from the posterolateral aspect of the FNT 1.6-11.1 mm from the stylomastoid foramen (5.4 ± 3.3 mm). It arose as a single branch (45.4%), or from a common trunk that divided into two (36.4%) or three branches (18.2%), with the other branches passing into the parotid gland. The PAN continued deep (63%), or lateral to the mastoid process (9.1%), or through the tissue of the parotid gland (27.3%). In all cases the PAN ran in a consistent, superficial location posterior to the external auditory meatus. The PAN takes a variable course; however, its consistent location behind the external auditory meatus makes it easily identifiable in superficial dissection, and therefore a potential surgical landmark for identifying the FNT.

Implications of a positive sentinel node in oral squamous cell carcinoma.

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. RESULTS: A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. CONCLUSIONS: The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans.

Versatility of the proximally pedicled anterolateral thigh flap and its use in complex abdominal and pelvic reconstruction.

BACKGROUND: The anterolateral thigh flap was described by Song et al. in 1984. Although more usually used as a free flap, it also has remarkable versatility as a pedicled flap. There are, however, no well-established guidelines that exist to define the extent of defects that can be reconstructed using this flap. In this article, the authors evaluate their experience with consecutive cases of the pedicled anterolateral thigh flap in complex abdominal and pelvic reconstruction. METHODS: A retrospective review of medical records and photographic archives was performed looking at 28 proximally pedicled anterolateral thigh flaps in 27 patients. RESULTS: The authors identified the arcs of rotation achieved, the types of defects reconstructed, points of surgical technique that enhanced their results, and some pitfalls of this flap. Useful points of surgical technique identified included suprafascial flap harvesting, extended harvesting of fascia, utilization of fascia to protect the pedicle, harvesting as a composite flap with the vastus lateralis, prudent preservation of large perforators that transgress the lateral aspect of the rectus femoris, synergistic use with a sartorius "switch," complete flap deepithelialization to fill dead space, and simple conversion to a free flap when pedicle length is inadequate. Pitfalls identified included the increased risk of pedicle avulsion in the morbidly obese, the risk of atherosclerotic plaque embolization in an atheromatous pedicle, and the potential inadequacy of thigh fascia for reconstituting abdominal wall integrity. CONCLUSIONS: This versatile flap has a wide arc of rotation. Multiple surgical modifications can be employed to tailor the flap to individual patient needs.