Survival after Ivor Lewis versus McKeown esophagectomy for cancer: propensity score matched analysis.

It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

Evolution of the surgical technique of minimally invasive Ivor-Lewis esophagectomy: description according to the IDEAL framework.

Totally minimally invasive Ivor-Lewis esophagectomy (Ivor Lewis TMIE) is a technically challenging procedure and is associated with a learning curve. Refinement of surgical technique is an important part of this learning curve. However, detailed descriptions of these refinements according to the idea, development, exploration, assessment, and long-term follow-up (IDEAL) framework are lacking and this study was undertaken to fill this knowledge gap. From 2010 until 2016, all consecutive patients (n = 164) were included from the first patient undergoing Ivor Lewis TMIE. Surgical reports were analyzed and surgeons were interviewed to determine surgical refinements. These data were used to describe the transition of the surgical technique from IDEAL stage IIB to stage III. The main findings were that four refinements were made to the surgical procedure in IDEAL stage IIB: (1) At case 9, the use of the 25 mm OrVil was abandoned, exchanged for a 28 mm EEA stapler and a large omental wrap around the anastomosis was introduced; (2) at case 27, the omental wrap was reduced in volume; (3) at case 60, the omental wrap was refined to cover the full 360° of the anastomosis and (4) at case 77, the fixation of the anvil with the Endostitch was replaced by fixation with two Endoloops®. During the transition from IDEAL stage IIB to stage III, the incidence of anastomotic leakage decreased from 26.0% to 4.6% (P < 0.001) and the incidence of textbook outcome increased from 31.2% to 47.1% (P = 0.039). In conclusion, this study describes the surgical refinements that were made during the progression of Ivor Lewis TMIE from IDEAL stage IIB to IDEAL stage III. During IDEAL stage IIB, postoperative outcome improved as surgical proficiency was gained and the technique was refined.

Neuronal anion exchange proteins in Alzheimer's disease pathology.

Anion exchange (AE) proteins are present in human neurons in the brain. Immunohistochemical data indicate that their apparent expression level increases with age, and especially with degeneration in Alzheimer's disease-affected brain areas. The increase in immunoreactivity is probably caused by changes in AE structure that lead to an increased accessibility of hitherto hidden epitopes. These epitopes correspond to regions in the membrane domain that are involved in generation of senescent cell-specific antigen from AE1 in aging erythrocytes. Elucidation of the molecular nature of these changes and the underlying mechanisms will lead to insight in the processes that govern aging- and degeneration-associated perturbation of membrane integrity. The functional consequences of changes in AE structure may range from acidosis and disturbance of cytoskeleton integrity to untimely or impaired recognition of neurons by microglia.

Involvement of neuronal anion exchange proteins in cell death in Alzheimer's disease.

Anion exchange (AE) proteins are present in human neurons in the brain. Immunohistochemical data indicate that their apparent expression level increases with age, and especially with degeneration in Alzheimer's disease-affected brain areas. The increase in immunoreactivity is probably caused by changes in AE structure that lead to an increased accessibility of hitherto hidden epitopes. These epitopes correspond to regions in the membrane domain that are involved in generation of senescent cell-specific antigen from AE1 in aging erythrocytes. Elucidation of the molecular nature of these changes and the underlying mechanisms, will lead to insight in the processes that govern aging- and degeneration-associated perturbation of membrane integrity. AE-mediated chloride/bicarbonate exchange is a major component in the regulation of intracellular pH. The functional consequences of changes in AE structure may range from acidosis, disturbance of cytoskeleton integrity, and untimely or impaired recognition of cells by components of the immune system, such as microglia. A molecular and physiological description of these changes will establish AE proteins as valuable tools in elucidating the processes of normal aging, and the disturbances in aging-related diseases such as Alzheimer's disease.

Expression of alpha B-crystallin in Alzheimer's disease.

alpha B-crystallin is a member of the small heat-shock protein family. Under pathological conditions, the expression of alpha B-crystallin increases in proliferating astrocytes, which suggests that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases. Immunoblotting and immunohistochemical methods were used for the detection of alpha B-crystallin in the brains of Alzheimer's disease (AD) patients and nondemented controls. An increase in alpha B-crystallin expression was found in the brains of AD patients. Immunoreaction was present in reactive astrocytes, microglia, and oligodendrocytes, indicating that all types of glia respond to the stress associated with AD pathology. Colocalization of GFAP and alpha B-crystallin was found in fibrous astrocytes. However, the intensity and range of alpha B-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of alpha B-crystallin is not a marker for gliosis in AD. Immunoreactivity to alpha B-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of alpha B-crystallin with amyloid deposition in AD.

The olfactory bulb in Alzheimer disease: a morphologic study of neuron loss, tangles, and senile plaques in relation to olfaction.

Complete pairs of olfactory bulbs of six Alzheimer disease (AD) patients and of six age- and sex-matched controls were morphologically investigated using a random systematic sampling procedure. The total number of cells and the number of mitral cells were the same for controls and patients, but the volume of the bulb and the number of neurons in the anterior olfactory nucleus (AON) were decreased in AD patients. The loss of AON neurons was limited to the younger AD patients and was very severe (75%). Neurofibrillary tangles (NFT) and senile plaques (SP) were found in controls, but they were more frequent in AD, especially in the younger cases. A new finding was the occurrence of very large numbers of so-called diffuse or "very primitive plaques" with the methenamine-silver stain (MS-SP). NFT and SP were limited to the AON but MS-SP also occurred in other parts of the bulb. The data are discussed in relation to olfaction, and it was concluded that odor identification is processed in central rather than in peripheral olfactory structures.

Erythrocyte band 3-like protein immunoreactivity in the human brain cortex.

The immunoreactivity of erythrocyte band 3 (B3-IR)-related protein was estimated on cortex biopsies from the brains of 33 patients varying in age from 14-week-old fetus until 67 years of life. B3-IR was not a feature of embryonic brains. A positive reaction was restricted to neurons. It appeared at early postnatal life, increased sharply until 9 years, and than stayed approximately stable between 17 and 67 years of age. The results indicate that there is a positive relation between the amount of neuronal band 3-like protein and the stage of human brain development.

Proteins immunologically related to erythrocyte anion transporter band 3 are altered in brain areas affected by Alzheimer's disease.

Proteins immunologically related to the human erythrocyte anion transporter band 3 are present in neurons of the human neocortex and hippocampus. Immunocytochemical studies show increased band 3 immunoreactivity in neurons in the brains of patients with Alzheimer's disease. Immunoblot studies show the presence of band 3-like molecules in brain membrane fractions, and suggest changes in expression and/or processing of band 3-like molecules in Alzheimer's disease-affected regions. We postulate that alterations in membrane-bound, band 3-like molecules may reflect termination of neuronal lifespan in Alzheimer's disease.

alpha B-crystallin is present in reactive glia in Creutzfeldt-Jakob disease.

alpha-Crystallin is a major eye lens protein, composed of two types of subunits, alpha A and alpha B. The alpha A subunit is restricted to the lens, but alpha B-crystallin has recently also been detected in non-lenticular tissues, including the nervous system. With the use of a polyclonal antiserum directed against a synthetic C-terminal peptide of human alpha B-crystallin, the presence of alpha B-crystallin could be demonstrated immunohistochemically in astrocytes in the brains of patients with Creutzfeldt-Jakob disease (CJD). Most intensive localization was observed in the spongiotic tissue representing abundant progressively changed astrocytes in CJD. In age-matched control brains weak positive reaction was located in individual oligodendroglia cells and subpial astrocytes. Prominent increase of alpha B-crystallin in pathological glia in CJD may represent a response to stress.

Galanin-like immunoreactivity within Ch2 neurons in the vertical limb of the diagonal band of Broca in aging and Alzheimer's disease.

The neuropeptide galanin is known to inhibit the evoked release of acetylcholine in ventral hippocampus of the rat. Co-localization of this peptide with choline acetyltransferase in neurons of the cholinergic septal nuclei has been demonstrated in the rat and non-human primate. The severe deficiency of the cholinergic hippocampal projection system arising mainly from the vertical limb nucleus of the diagonal band of Broca, also referred to as Ch2 region, is a constant finding in Alzheimer's disease, a disorder which is neuropathologically characterized by the appearance of senile plaques, neurofibrillary tangles and congophilic angiopathy in neo- and archicortical structures. In the present study for the first time galanin immunoreactivity in the human Ch2 region is morphologically investigated and related to the severity of hippocampal plaques and neurofibrillary tangles in Alzheimer's disease. An inverse relationship between decreasing galanin immunoreactivity in the Ch2 region and amounts of senile plaques and neurofibrillary tangles in the hippocampus is indicated. Considering the cholinergic deficiency in Alzheimer's disease as a secondary phenomenon to primary cortical and hippocampal lesions, and realizing the inhibitory effect of galanin upon acetylcholine release in hippocampus, this preliminary study suggests that a decreased galanin immunoreactivity in Ch2 in Alzheimer's disease, reflects a possible negative feedback mechanism to a degenerating cholinergic projection system.