Kevin West

A comparative histological evaluation of the ablations produced by microwave, cryotherapy and radiofrequency in the liver.

Aims: Complete tumour cell death is necessary for any ablative technique to be successful. Microwave tissue ablation (MTA), radiofrequency (RF) and cryotherapy (CT) are three methods of destroying liver tumours in situ. Unlike MTA, RF and CT rely on conduction of the thermal insult for their cytotoxicity, potentially affecting lesion uniformity. The aim of this study was to compare the uniformity of demarcation of lesions induced by MTA, RF and CT in the rat liver. Methods: Twenty‐one rats were assigned to each of the three ablative modalities. Results: All specimens exhibited macroscopically well‐demarcated lesions. Microscopically, the most clearly delineated lesions were induced by MTA with no intra‐lesional viable hepatocytes or peri‐vascular survival. All vessels and bile ducts had undergone complete necrosis. CT specimens showed more prominent inflammation at the lesion edge than MTA and peri‐vascular hepatocyte survival within the ablated volumes. RF showed hepatocyte survival in the ablated area and conspicuous peri‐vascular hepatocyte survival with evidence of a very irregular lesion edge. Cell viability was only assessed with H&E staining and not immunocytochemically. Conclusion: Unlike RF and CT, MTA induced microscopically well‐demarcated lesions, with no intralesional hepatocyte survival. Intralesional cell survival in RF and CT may be due to the relatively prolonged treatment times needed, allowing thermal energy to dissipate via blood flow. This is known as the heat sink effect and may contribute to the high local recurrence rates following treatment of larger tumours with RF and CT.

An evaluation of the prognostic significance of HLA‐DR expression in gastric carcinoma

The prognostic value of histochemical staining for HLA‐DR was assessed retrospectively in 52 “curative” gastrectomy specimens from patients with gastric carcinoma. In addition other tumor variables, including histologic type, degree of differentiation, extent of local spread, prominence of mononuclear infiltrate, tumor edge, and lymph‐node metastases, were examined. Sixty‐five percent of the tumors showed positive staining for HLA‐DR, and these tumors had a higher mean and median survival at 5 years compared with negative tumors. However, on multivariate analysis the difference was not statistically significant. The authors conclude that, although HLA‐DR staining is associated with tumors of better prognosis, it cannot be used as an independent prognostic factor. Of the other tumor variables, only lymph‐node status was of prognostic significance.

Changes in interleukin-1β and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections.

BACKGROUND Cytokine changes after microwave tissue ablation (MTA) were compared with hepatic resection, cryotherapy (CRYO), and radiofrequency ablation (RFA). Cytokine production was measured at various ablation volumes for each modality and correlated with the transitional inflammatory zone produced by the ablation techniques. METHODS Live rats underwent MTA, surgical resection, CRYO or RFA of 15%, 33%, or 66% of the total hepatic volume. Serum samples were collected preoperatively and at 1, 3, 6, 24, and 48 hours after surgery and analyzed for pro-inflammatory cytokines interleukin (IL)-1β and IL-6. RESULTS Significantly higher levels of both cytokines were present after CRYO and RFA compared with MTA, hepatic resection, or controls (P < .001). All animals survived except those undergoing RFA or CRYO of 66% of the hepatic volume, which died within 6 hours. Transitional zones produced after RFA were larger than those after CRYO or MTA, but no correlation was present with the amount of cytokines. CONCLUSIONS Large-volume MTA is associated with a significant decreased cytokine response and is well tolerated compared with RFA and CRYO.

Microwave ablation of the liver: a description of lesion evolution over time and an investigation of the heat sink effect

Aim: Microwave ablation has been successfully used to treat unresectable liver tumours for many years. However, despite its widespread use, there seems to be a relative paucity of experimental data regarding lesion evolution and the effects of any surrounding vasculature on ablation morphology. The aim of this study was to investigate the principal pathological changes in the liver following microwave ablation, in particular the heat sink effect. In addition we carefully reviewed the available literature to provide an overview of all relevant pathological studies. Methods: Microwave ablation was carried out on male rats at various distances from the hilum. Histological (H&E) and immunocytochemical (caspase 3) analyses of the lesion were performed at various time points; 0, 4, 24, 48 hours, 2 weeks and 1 month. A literature review was carried out using Medline, Embase and the Cochrane database to identify all relevant histological studies. Results: The lesion underwent complete coagulative necrosis and was extremely regular at the ablation edge with no evidence of any influence from surrounding blood vessels at all time points. H&E and caspase 3 results were consistent and microwave caused little collateral damage outside the intended ablation zone. Conclusion: This study suggests that microwave ablation is extremely concise and is minimally affected by the heat sink effect. Comparative investigations with other treatment modalities are required.

Heat Shock Protein 70 Expression Following Hepatic Radiofrequency Ablation is Affected by Adjacent Vasculature

BACKGROUND Heat shock proteins are a highly conserved family of stress response proteins. Members of the heat shock protein 70 (Hsp70) family prevent protein misfolding and aggregation. Following radiofrequency ablation of unresectable liver tumors an interface appears between the irreversibly damaged and normal liver. The fate of this transition zone is critical and is believed to be responsible for local recurrences. Hsp70 is expressed in response to thermal stress and may influence the fate of cells in this transitional zone. It is also recognized that the presence of large vessels or a perivascular location of tumors also influences the recurrence rate. The aim of this study is to examine the transition zone and observe the effect of local blood flow on ablation morphology and Hsp70 expression. METHODS Radiofrequency ablation was performed in 25 rats at various distances from the liver hilum. Tissue was retrieved and analysed at time points 0, 4, 24, 48 h, and 2 wk following treatment. Tissue was analyzed histologically with hematoxylin and eosin staining (H and E,) and immunohistochemically for Hsp70 expression. RESULTS All rats survived the procedure. H and E staining revealed previously unreported foci of apoptosis at the ablation edge and deep in the normal hepatic parenchyma. Hsp70 was expressed in the transition zone at 4 h and peaked at 24 h. The degree of Hsp70 expression was significantly influenced by the distance from surrounding vasculature. CONCLUSIONS This study reports several previously unreported findings. There is increased apoptosis distal to the ablated zone suggests leakage of radiofrequency (RF) current down blood vessels originating in the ablation zone. The degree of Hsp70 expression in the transition zone correlates with time after treatment and the size and location of any adjacent vasculature. These findings suggest that heat shock proteins may play a role in the ability of damaged cells to recover and survive at the periphery of an ablation zone.

The criminal justice system's considerations of so-called near-virtual autopsies: the East Midlands experience

Background While several research groups champion the potential for postmortem CT (PMCT) to replace the invasive postmortem (PM), many questions still remain. Aims Perhaps the two most important questions are whether PMCT can provide the same level of information as an invasive PM, and arguably more importantly, can it meet the needs of the end users of the PM report. Through a comparative analysis of invasive post-mortem and CT findings and a questionnaire based qualitative thematic analysis, the authors have sought to answer these questions. Results and Conclusion Here, the authors show that PMCT is good at providing accurate causes of death and that the interpretation of cases is not significantly altered by the absence of histology. The authors show that in straightforward trauma deaths such as road traffic incidents, there exists the potential for the replacement of the invasive PM by PMCT examination. However, as yet, PMCT cannot provide all of the information that is expected by the criminal justice system in complex forensic cases.

Diagnostic accuracy of post-mortem CT with targeted coronary angiography versus autopsy for coroner-requested post-mortem investigations: a prospective, masked, comparison study

Summary Background England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations. Methods In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majestys (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified. Findings Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect the overall population data for cause of death (p≥0·31). PMCTA was better at identifying trauma and haemorrhage (p=0·008), whereas autopsy was better at identifying pulmonary thromboembolism (p=0·004). Interpretation For most sudden natural adult deaths investigated by HM Coroners, PMCTA could be used to avoid invasive autopsy. The gold standard of post-mortem investigations should include both PMCT and invasive autopsy. Funding National Institute for Health Research.

Renal effects of microwave ablation compared with radiofrequency, cryotherapy and surgical resection at different volumes of the liver treated

Background: Renal changes after microwave tissue ablation (MTA) were compared with those following hepatic resection, cryotherapy (CRYO), and radiofrequency ablation (RFA). Structural damage producing renal impairment has been assessed directly by examining tissue specimens and by serum analysis for two sensitive biomarkers, retinol binding protein (RBP) and the heat shock protein 70 (HSP‐70) for each modality at different ablation volumes.

Analysis of antigen receptor genes in Hodgkin's disease.

AIM--To analyse the configuration of the antigen receptor genes in Hodgkins disease. METHODS--DNA extracted from 45 samples of Hodgkins disease was analysed using Southern blotting and DNA hybridisation, using probes to the joining region of the immunoglobulin heavy chain gene, the constant region of kappa immunoglobulin light chain gene, and the constant region of the beta chain of the T cell receptor gene. RESULTS--A single case of nodular sclerosing disease showed clonal rearrangement of the immunoglobulin heavy and light chain genes, all other samples having germline immunoglobulin genes. The nature of the clonal population in the diseased tissue is uncertain, because the intensity of the rearranged bands did not correlate with the percentage of Reed-Sternberg cells present. The T cell receptor genes were in germline configuration in all the samples. CONCLUSIONS--Antigen receptor gene rearrangement is a rare finding in unselected cases of Hodgkins disease.

Is emergency laryngectomy a waste of time

INTRODUCTION Patients who present with airway obstruction due to carcinoma of the larynx may be managed by tracheotomy followed by definitive tumor surgery at a later date. An alternative is emergency laryngectomy, defined as total laryngectomy performed within 24 hours, for a previously untreated and undiagnosed malignancy. In this study, we compare and contrast the outcome of 13 patients managed by tracheotomy and delayed laryngectomy to another group of patients, previously reported, managed by emergency laryngectomy. MATERIALS AND METHODS Stridor due to malignant laryngeal neoplasm was treated by tracheotomy and delayed definitive laryngectomy in 13 patients. In every case, the tracheostomy site was removed with a surgical specimen. A comparison of the survival data was performed with earlier reported series of 13 emergency laryngectomies using the Wilcoxon log rank method. RESULTS All patients were followed for a minimum of 24 months. Seven patients underwent postoperative radiotherapy. Two of these patients (15%) developed peristomal recurrence at 6 and 22 months respectively. Both died of disease. Six patients from each group survived disease free for a minimum of 24 months. No significant correlation was found between the time delay of definitive surgery and survival (P > .5). DISCUSSION This series suggests that emergency laryngectomy offers patients no survival advantage. Emergency laryngectomy does, however, have several disadvantages. These include the necessity to rely on frozen section analysis, the difficulty in obtaining expert anesthetic support, and the inability to provide thorough and complete nutritional and metabolic work up before major surgery. Finally, the psychologic aspects of radical surgery for patient and family cannot be adequately addressed. We conclude that stomal recurrence is as much a function of extensive disease at presentation as of preliminary tracheotomy. Emergency laryngectomy is not a superior treatment modality and offers no particular survival advantage.