Jennifer Rusby

Adenovirus gene transfer causes inflammation in the brain.

We report that injecting an E1-deleted, non-replicating, human adenovirus type 5 vector into the brain leads to an inflammatory response. Much of this inflammation is induced directly by the virion particles themselves rather than through the expression of new proteins from the vector. The severity of inflammation was found to depend on the strain of inbred rat used: PVG rats have less inflammation than AO rats in response to a vector injection. Twelve hours after injection of adenovirus vectors into the striatum of AO rats, leukocytes were seen marginating to the walls of nearby blood vessels. By two days there was a large increase in major histocompatibility complex class I expression and a heavy infiltration of leukocytes, mainly macrophages and T cells. Retrograde transport of adenovirus to neurons of the substantia nigra was associated with a delayed and less intense inflammation at this distant site. Although AO and PVG rats showed comparable responses in the striatum up to six days, at later times PVG rats had less intense inflammation. In spite of the inflammatory response, vector-driven expression of the marker protein beta-galactosidase and an adenovirus early protein was seen for at least two months following the injection, although expression declined with time. The observation that adenovirus gene transfer leads to an inflammatory response in the brain must be taken into account when planning and interpreting experiments with these vectors. Furthermore, we conclude that using an appropriate strain of rat can diminish some aspects of the inflammation.

Nipple‐sparing mastectomy

Although effective local control is the primary goal of surgery for breast cancer, the long‐term aesthetic outcome is also important. Nipple‐sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed.

Occult Nipple Involvement in Breast Cancer: Clinicopathologic Findings in 316 Consecutive Mastectomy Specimens

PURPOSE Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement. PATIENTS AND METHODS Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin. RESULTS Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS. CONCLUSION Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy.

Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy

This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple‐sparing mastectomy.

Nipple‐Sparing Mastectomy: Lessons from Ex Vivo Procedures

Abstract:  Moderate size series have reported successful nipple‐sparing mastectomy using a variety of surgical techniques. This study aimed to understand which aspects of these techniques are safe, necessary, and successful. Eight skin‐sacrificing mastectomy specimens were used as ex vivo models of nipple‐sparing mastectomy. After inking the resection margins of the specimen, the skin ellipse was elevated in the subcutaneous plane using a scalpel. The retroareolar breast tissue was taken as a margin specimen. The nipple was inverted and the nipple core removed. The hollowed‐out nipple remnant (which would have remained with the patient in a true nipple‐sparing mastectomy) was submitted for confirmatory histopathologic analysis. Precise identification of the duct margin directly beneath the nipple proved difficult once the duct bundle had been divided. Successful retroareolar margin identification was achieved by grasping the duct bundle with atraumatic forceps as soon as it became exposed. A cut made below and above the forceps resulted in a full cross‐section of the duct bundle. Nipple core tissue was difficult to excise in one piece and cannot be oriented, thus complete evaluation of the specimen required examination of multiple levels. Histologic artifacts caused by freezing may be present in frozen sections of nipple core and retroareolar margin specimens; the impact of such changes must be considered when developing institutional protocols for this procedure. Evaluation of the hollowed‐out nipple revealed that the inverted nipple must be substantially thinned to remove all ducts. Modification of technique resulted in more complete excision of duct tissue. This series of ex vivo procedures provides information that can be used to modify surgical and pathologic techniques for nipple‐sparing mastectomy. When performing nipple‐sparing mastectomy for breast cancer, these measures may be advisable as complements to careful patient selection.

Nipple-sparing mastectomy in women with large or ptotic breasts

Nipple-sparing mastectomy has been shown to have equivalent oncological outcome to skin-sparing mastectomy in carefully selected patients and acceptable rates of nipple necrosis. Its role in risk-reducing mastectomy is established. However, it is widely considered that nipple-sparing mastectomy is only suitable for women with small and non-ptotic breasts. The reasons cited are that an excessive skin envelope may result in higher rates of nipple necrosis or in nipples that are poorly positioned on the reconstructed breast mound. A malpositioned, preserved nipple may result in a significant aesthetic compromise compared with a correctly positioned reconstructed nipple. Skin-reducing mastectomy utilising a Wise pattern approach has been described for women undergoing immediate implant reconstruction. It is most suitable for women with ptotic or large breasts who can accommodate a mastopexy or reduction and are willing to consider contralateral symmetrising surgery. We report a modification of the skin-reducing mastectomy to allow preservation of the nipple in women who would not otherwise be considered for this technique because of unsuitable breast shape.

Sentinel lymph node biopsy after previous axillary surgery: A review.

BACKGROUND The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers. METHODS We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND). RESULTS There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up. CONCLUSION SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery.

Determinants of optimal mastectomy skin flap thickness.

There is a limited evidence base to guide surgeons on the ideal thickness of skin flaps during mastectomy. Here the literature relevant to optimizing mastectomy skin flap thickness is reviewed, including anatomical studies, oncological considerations, factors affecting viability, and the impact of surgical technique and adjuvant therapies.

Squamous cell carcinoma arising in a tall cell papillary carcinoma of the thyroid.

Transformation of differentiated thyroid cancer into poorly differentiated carcinoma is rare. This report describes a case in which preoperative fine needle aspiration suggested a squamous cell carcinoma whereas needle core biopsy favoured an undifferentiated carcinoma of probable thyroid origin. Histology of the subsequent total thyroidectomy specimen revealed a biphasic tumour comprising areas of tall cell papillary carcinoma merging with moderately to poorly differentiated squamous cell carcinoma. The immunohistochemical findings are discussed in detail.

Left‐sided gall bladder: A diagnostic and surgical challenge

A gall bladder located on the left side of the round ligament and partially embedded in the under-surface of the left lobe (segment III), the so-called ‘left-sided gall bladder’, is an uncommon anomaly. The first published account of left-sided gall bladder was in 18861 and since then 105 cases of left-sided gall bladder have been reported.2 The present paper describes a case of left-sided gall bladder and discusses the clinical importance of this uncommon anomaly.