Guidelines for Perioperative Care in Elective Abdominal and Pelvic Surgery at Primary and Secondary Hospitals in Low-Middle-Income Countries (LMIC's): Enhanced Recovery After Surgery (ERAS) Society Recommendation.

BACKGROUND: This is the first Enhanced Recovery After Surgery (ERAS®) Society guideline for primary and secondary hospitals in low-middle-income countries (LMIC's) for elective abdominal and gynecologic care. METHODS: The ERAS LMIC Guidelines group was established by the ERAS® Society in collaboration with different representatives of perioperative care from LMIC's. The group consisted of seven members from the ERAS® Society and eight members from LMIC's. An updated systematic literature search and evaluation of evidence from previous ERAS® guidelines was performed by the leading authors of the Colorectal (2018) and Gynecologic (2019) surgery guidelines (Gustafsson et al in World J Surg 43:6592-695, Nelson et al in Int J Gynecol Cancer 29(4):651-668). Meta-analyses randomized controlled trials (RCTs), prospective and retrospective cohort studies from both HIC's and LMIC's were considered for each perioperative item. The members in the LMIC group then applied the current evidence and adapted the recommendations for each intervention as well as identifying possible new items relevant to LMIC's. The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE) methodology was used to determine the quality of the published evidence. The strength of the recommendations was based on importance of the problem, quality of evidence, balance between desirable and undesirable effects, acceptability to key stakeholders, cost of implementation and specifically the feasibility of implementing in LMIC's and determined through discussions and consensus. RESULTS: In addition to previously described ERAS® Society interventions, the following items were included, revised or discussed: the Surgical Safety Checklist (SSC), preoperative routine human immunodeficiency virus (HIV) testing in countries with a high prevalence of HIV/AIDS (CD4 and viral load for those patients that are HIV positive), delirium screening and prevention, COVID 19 screening, VTE prophylaxis, immuno-nutrition, prehabilitation, minimally invasive surgery (MIS) and a standardized postoperative monitoring guideline. CONCLUSIONS: These guidelines are seen as a starting point to address the urgent need to improve perioperative care and to effect data-driven, evidence-based care in LMIC's.

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial.

Derivation, Validation and Application of a Pragmatic Risk Prediction Index for Benchmarking of Surgical Outcomes.

BACKGROUND: Despite the existence of multiple validated risk assessment and quality benchmarking tools in surgery, their utility outside of high-income countries is limited. We sought to derive, validate and apply a scoring system that is both (1) feasible, and (2) reliably predicts mortality in a middle-income country (MIC) context. METHODS: A 5-step methodology was used: (1) development of a de novo surgical outcomes database modeled around the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) in South Africa (SA dataset), (2) use of the resultant data to identify all predictors of in-hospital death with more than 90% capture indicating feasibility of collection, (3) use these predictors to derive and validate an integer-based score that reliably predicts in-hospital death in the 2012 ACS-NSQIP, (4) apply the score in the original SA dataset and demonstrate its performance, (5) identify threshold cutoffs of the score to prompt action and drive quality improvement. RESULTS: Following step one-three above, the 13 point Codman's score was derived and validated on 211,737 and 109,079 patients, respectively, and includes: age 65 (1), partially or completely dependent functional status (1), preoperative transfusions ≥4 units (1), emergency operation (2), sepsis or septic shock (2) American Society of Anesthesia score ≥3 (3) and operative procedure (1-3). Application of the score to 373 patients in the SA dataset showed good discrimination and calibration to predict an in-hospital death. A Codman Score of 8 is an optimal cutoff point for defining expected and unexpected deaths. CONCLUSION: We have designed a novel risk prediction score specific for a MIC context. The Codman Score can prove useful for both (1) preoperative decision-making and (2) benchmarking the quality of surgical care in MIC's.

An Online Tool for Global Benchmarking of Risk-Adjusted Surgical Outcomes.

BACKGROUND: Increasing evidence demonstrates significant variation in adverse outcomes following surgery between countries. In order to better quantify these variations, we hypothesize that freely available online risk calculators can be used as a tool to generate global benchmarking of risk-adjusted surgical outcomes. METHODS: This is a prospective cohort study conducted at an academic teaching hospital in South Africa (GSH). Consecutive adult patients undergoing major general or vascular surgery who met the ACS-NSQIP inclusion criteria for a 3-month period were included. Data variables required by the ACS risk calculator were prospectively collected, and patients were followed for 30 days post-surgery for the occurrence of endpoints. Calculating observed-to-expected ratios for ten outcome measures of interest generated risk-adjusted outcomes benchmarked against the ACS-NSQIP consortium. RESULTS: A total of 373 major general and vascular surgery procedures met the inclusion criteria. The GSH operative cohort varied significantly compared to the 2012 ACS-NSQIP database. The risk-adjusted O/E ratios were significant for any complication O/E 1.91 (95 % CI 1.57-2.31), surgical site infections O/E 4.76 (95 % CI 3.71-6.01), renal failure O/E 3.29 (95 % CI 1.50-6.24), death O/E 3.43 (95 % CI 2.19-5.11), and total length of stay (LOS) O/E 3.43 (95 % CI 2.19-5.11). CONCLUSION: Freely available online risk calculators can be utilized as tools for global benchmarking of risk-adjusted surgical outcomes.

Factors associated with adverse events after emergency laparotomy in Cape Town, South Africa: identifying opportunities for quality improvement.

BACKGROUND: Surgical outcomes research is limited in areas of the world with the greatest unmet surgical need and likely greatest variation in outcomes. Measurement alone may improve outcomes-the so-called Hawthorne effect. The purpose of this multicenter cohort study was to identify factors that are both feasible to collect and are associated with a major adverse event following a targeted procedure in Cape Town, South Africa. METHODS: A collaborative of four acute care surgical units was formed to develop a data set with minimal data burden describing outcomes after an emergency exploratory laparotomy during a 3-mo period (February-April 2015). Controlling for patient, problem, provider, procedure and process predictors, multivariate models were built to identify risk factors for a major adverse event and higher resource use after surgery in our collaborative. RESULTS: The outcomes of 450 exploratory laparotomies from the four participating hospitals were audited, 319 (70.9%) were for non-trauma and 131 (29.1%) were for trauma. The major adverse event rate was 15.7% (95% CI 12.6-19.4). In the multivariate analysis, factors associated with the primary outcome included age, American Society of Anesthesia score of greater than 2, bowel resection, preoperative CT scan, and a nontherapeutic laparotomy. A major adverse event was associated with all three outcomes assessing increased resource utilization. CONCLUSIONS: This study supports the comparative outcome assessment of a high-volume or high-risk procedure as a proxy for measuring the quality of care provided in a surgical collaborative. Such an exercise can identify opportunities for quality improvement.

Copy Number Analysis of the DLX4 and ERBB2 Genes in South African Breast Cancer Patients.

Breast cancer is one of the main causes of cancer death among South African women. Although several risk factors can be attributed to the observed high mortality rate, the biology of the tumors is not extensively investigated. Copy number gain of the DLX4 homeobox gene has been observed in breast cancer in association with poor prognosis and specific racial groups. Therefore, we aimed to assess the copy number and prognostic role of DLX4 in breast cancer from South African patients. Due to the co-location of ERBB2 and DLX4 in the 17q21 region, its copy number was also evaluated. Our results in the analysis of 66 cases demonstrated copy number gains of DLX4 and ERBB2 in 24.1 and 29.7% of the cases, respectively. Linear regression analysis showed no dependency between the copy number alterations in these genes. Although not significant, patients with DLX4 and ERBB2 gains presented a higher frequency of advanced-grade tumors. In addition, copy number alterations of these genes were not significantly differently observed in the 3 main racial groups of the Western Cape population: Colored, White, and Black. These findings indicate that gains of DLX4 and ERBB2 occur in South African breast cancer patients irrespectively of their race and factors known to influence prognosis.

Pre-operative diagnosis of thyroid cancer: clinical, radiological and pathological correlation.

AIM: Ultrasonography and fine-needle aspiration biopsy (FNAB) are the mainstays of diagnosing thyroid cancer accurately and reducing the number of diagnostic lobectomies. No benchmark for diagnostic accuracy has been published in the South African context. This single-institution study addresses this deficit. METHODS: The oncology, pathology and surgical records of all patients diagnosed with thyroid carcinoma from 2004 to 2010 at Groote Schuur Hospital, Cape Town, South Africa, were reviewed and data were recorded on a standardised confidential proforma. The findings on pre-operative clinical assessment, ultrasound and FNAB were correlated with the histopathology results. Diagnostic accuracy for thyroid cancer was determined by correlating pre-operative investigations with the final diagnosis. Sensitivity of ultrasound and FNAB were calculated. RESULTS: A total of 109 patients, 79 female and 30 male, were identified. The majority (99, 90.8%) had well-differentiated thyroid cancers (56 papillary, 30 follicular, 10 mixed and 3 Hurtle cell carcinomas). There were 6 anaplastic and 4 medullary carcinomas. Of the 109 patients 38 had a definite pre-operative diagnosis, in 61 a malignant tumour was suspected, and 10 had surgery for benign disease. FNAB was inadequate in 11 cases and the findings indicated a benign lesion in 47, a suspicious lesion in 13 and a malignant lesion in 38 patients diagnosed with thyroid carcinoma. FNAB diagnosed all patients with medullary and anaplastic carcinoma but less than half of those with well-differentiated thyroid carcinoma. Ultrasound scans detected at least one suspicious feature in 44 patients. Microcalcification was the most common sign. CONCLUSION: The rate of pre-operative diagnosis of well-differentiated thyroid carcinomas in this unit is under 50%, well below international norms. Our standard practice needs to change to include ultrasound-guided FNAB and standardised reporting of high-resolution ultrasound and cytology, before reassessment of our diagnostic accuracy.

A Delphi study to guide the development of a clinical indicator tool for palliative care in South Africa.

BACKGROUND:  The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends 'a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs'. AIM:  This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC. SETTING:  The South African healthcare setting. METHODS:  A Delphi study was considered suitable as a methodology to develop consensus. The methodology was based on the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies to ensure rigour and transparency in conducting and reporting. Six different Delphi rounds were used to develop consensus. Each round allowed participants to anonymously rate statements with predefined rating scales. RESULTS:  Cognisant of the disparities in healthcare provision and access to equitable healthcare in South Africa, the expert advisory group recommended, especially for South Africa, that 'this tool is for deteriorating patients with an advanced life-limiting illness where all available and appropriate management for underlying illnesses and reversible complications has been offered'. The expert advisory group felt that disease-specific indicators should be described before the general indicators in the South African indicators tool, so all users of the tool orientate themselves to the disease categories first. This study included three new domains to address the South African context: trauma, infectious diseases and haematological diseases. General indicators for PC aligned with the original Supportive and Palliative Care Indicators Tool (SPICT) tool. CONCLUSION:  The Supportive and Palliative Care Indicators Tool for South Africa (SPICTTM-SA) is a simple screening tool for South Africa that may assist HCPs to recognise patients who may have unmet PC needs.

Papillary thyroid carcinoma presenting as miliary nodules on chest roentgenogram in the paediatric setting: A case report.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common carcinoma to occur in childhood with a peak incidence between 11-17 years, and typically presents with advanced locoregional disease. Pulmonary metastases are seen in up to 46% of cases and should enter the differential diagnosis of miliary nodules seen on chest roentgenogram, even in regions where tuberculosis is endemic. PRESENTATION OF CASE: An 11-year-old male presented with a short history of cough, shortness of breath and constitutional symptoms. Examination revealed cervical lymphadenopathy and diffuse bilateral nodular infiltrates on the chest roentgenogram. Investigation for Mycobacterium tuberculosis was negative and this initiated biopsy of a cervical lymph node. Histopathological examination revealed metastatic PTC. Ultrasonography and magnetic resonance imaging (MRI) were performed for preoperative staging. The patient subsequently underwent total thyroidectomy with selective neck dissection. DISCUSSION: There are several potential causes when dealing with miliary nodules on chest roentgenogram. Thorough interrogation of the clinical, radiological, pathological and microbiological data is required to arrive at the correct diagnosis. Postoperative adjuvant therapy with radioactive iodine is recommended in children with metastatic disease, but this should be restricted preferably to a single dose to avoid the complication of pulmonary fibrosis. CONCLUSION: This case highlights the differential diagnostic considerations of a patient presenting with constitutional symptoms and a miliary pattern on chest roentgenogram. Carcinomas are uncommon in children but should not be forgotten.

Managing sarcoma: where have we come from and where are we going?

Sarcomas are a heterogeneous group of neoplasms of mesenchymal origin. Approximately 80% arise from soft tissue and 20% originate from bone. To date more than 100 sarcoma subtypes have been identified and they vary in molecular characteristics, pathology, clinical presentation and response to treatment. While sarcomas represent <1% of adult cancers, they account for approximately 21% of paediatric malignancies and thus pose some of the greatest risks of mortality and morbidity in children and young adults. Metastases occur in one-third of all patients and approximately 10-20% of sarcomas recur locally. Surgery in combination with preoperative and postoperative therapies is the primary treatment for localized sarcoma tumours and is the most promising curative possibility. Metastasized sarcomas, on the other hand, are treated primarily with single-agent or combination chemotherapy, but this rarely leads to a complete and robust response and often becomes a palliative form of treatment. The heterogeneity of sarcomas results in variable responses to current generalized treatment strategies. In light of this and the lack of curative strategies for metastatic and unresectable sarcomas, there is a need for novel subtype-specific treatment strategies. With the more recent understanding of the molecular mechanisms underlying the pathogenesis of some of these tumours, the treatment of sarcoma subtypes with targeted therapies is a rapidly evolving field. This review discusses the current management of sarcomas as well as promising new therapies that are currently underway in clinical trials.

Perianal synovial sarcoma treated postoperatively with Iodine-125 brachytherapy: Technical details.

PURPOSE: A 23-year-old lady had an incompletely excised perianal sarcoma. Brachytherapy as the sole treatment, rather than further surgery or external beam radiotherapy, was considered to be the best option with the least morbidity. METHODS AND MATERIALS: Although brachytherapy techniques with iridium-192 for anal and rectal carcinoma are well described using a perianal template, the size of the template was not suitable for a two-plane implant that needed to be in situ for about 4 days. An anal canal applicator was designed, which carried three templates about 15 mm apart inside it, to ensure accurate alignment of the tubes, and an inferior template that was 90 mm from the perianal skin. Three inner and three outer tubes of iodine-125 seeds were designed to treat a 2 o'clock h wedge of perianal tissue as a temporary implant. A thin metal shield was placed around a hole to protect the uninvolved anal canal. The tubes were inserted under general anesthetic and delivered a dose of 59 Gy at 0.8 Gy/h over 75 h. A spinal anesthetic was maintained for the duration of the insertion. RESULTS: The treatment was well tolerated, and the patient is well and clear of disease 6 years later with minimal morbidity. CONCLUSIONS: Iodine-125 is a low-energy isotope, readily available in our unit, that can be easily screened to reduce morbidity to surrounding normal tissues. In the form of seeds, it provides a flexible system that can be adapted to different tumor sites as required, as illustrated in this case.

A multicentre evaluation of emergency abdominal surgery in South Africa: Results from the GlobalSurg-1 South Africa study.

BACKGROUND: GlobalSurg-1 was a multicentre, international, prospective cohort study conducted to address the global lack of surgical outcomes data. Six South African (SA) hospitals participated in the landmark surgical outcomes study. In this subsequent study, we collated the data from these six local participants and hypothesised that the location of surgery was an independent risk factor for an adverse outcome following emergency intraperitoneal surgery. METHODS: Participating hospitals contributed 30-day outcomes data of consecutive emergency intraperitoneal surgical operations performed during a 2-week period between July and November 2014. The six heterogeneous hospital cohorts were compared by categorical confounders. The primary outcome measure was in-hospital mortality; secondary outcome measures were in-hospital morbidity and length of stay of >14 days. The unadjusted association between hospital and adverse outcome and the univariate association between categorical confounders and adverse outcome were tested. Significant associations were further tested by a multivariate stepwise forward logistic regression model built for each outcome of interest. RESULTS: Six hospitals (designated 1 - 6) contributed outcomes data for 169 operations. The mean age of the patients was 34.9 years (range 9 - 82), 116 (68.6%) were male, and the majority (37.2%) presented as a result of trauma. Hospital 5 was associated with 76-fold increased odds of in-hospital death and 58-fold increased odds of a major in-hospital complication, and hospital 3 was associated with 3-fold increased odds of any in-hospital complication. The final model predicting in-hospital death had a receiver operating characteristic curve statistic of 0.8892. CONCLUSION: The hospital is an independent risk factor for risk-adjusted adverse outcomes following emergency intraperitoneal surgery in SA.

Collaboration is key to strengthening surgical research capacity in sub-Saharan Africa.

The paucity of research in areas of greatest clinical need must be addressed urgently. We propose a model of collaboration in an era of information systems and emerging mobile health technology that has had significant success across the UK and has shown early encouraging results in South Africa (SA). We foresee that recent examples of surgical research collaboratives in SA will continue to promote regional, national and international 'hub-and-spoke' models and ultimately increase the South-South collaboration that is urgently needed to diffuse the skills and knowledge required to address the unmet surgical need in sub-Saharan Africa.

Role of splenectomy for immune thrombocytopenic purpura (ITP) in the era of new second-line therapies and in the setting of a high prevalence of HIV-associated ITP.

BACKGROUND: New agents are being used as second-line treatment for immune thrombocytopenia (ITP) and have brought into question the relevance of splenectomy for steroid-resistant ITP. METHODS: We retrospectively analysed 73 patients who underwent splenectomy for ITP at our institution over an 11-year period. The median follow-up period was 25 months; patients with follow-up of <1 month were excluded. The outcomes of splenectomy were compared in HIV-positive v. HIV-negative patients. RESULTS: The rate of complete response was 83%, and response was sustained for at least 1 year or until latest follow-up in 80% of patients. Twelve patients were HIV-positive. Splenectomy was laparoscopic in 43 patients (62%) with an overall 16% complication rate. The 90-day mortality rate was 1.38%. There was no statistically significant difference in response or complication rate in the HIV-positive patients. There was a statistically significant (p=0.003) poorer response to splenectomy in the patients with steroid-resistant ITP. CONCLUSION: Splenectomy is effective and safe irrespective of HIV status and remains an appropriate second-line treatment for ITP. Further research is needed to corroborate our finding of lower response in patients who are steroid-resistant, as this might be a subgroup of patients who may benefit from thrombopoietin agonists as second line therapy.

A study of the patient factors affecting reconstruction after mastectomy for breast carcinoma.

Breast shape may be retained after surgery for breast cancer with either wide local excision (WLE) and radiotherapy or mastectomy (M) and immediate reconstruction (M+R). We determined the proportions of patients who would be suitable for these options, would accept them, and if they declined M+R their reasons for doing so. Over a 10-month period 177 women were assessed at a combined breast clinic by general and plastic surgeons and by radiation oncologists. A prospective record was made of the patient demographic data, the clinical decisions (and their reasons), and the patient choices (and their reasons). A transverse rectus abdominis myocutaneous flap was the commonest method of reconstruction. One hundred thirty-five (76%) were judged to be suitable for locoregional surgery. Of these M+R was offered to 83 patients, whereas 53 were not considered because of combinations of cosmetic considerations (31), risk factors (25), old age (13), and oncological factors (nine). Fifty-one of the 83 (61%) offered M+R declined it because they preferred a simpler procedure (34), regarded breast appearance as unimportant (15), preferred breast conservation (five), did not have a partner (three), felt that they were too old (two), or had religious reasons (two). Ultimately 69 (51%) underwent M, 34 (25%) WLE, and 32 (24%) M+R. There was no correlation between acceptance or not of M+R and age, race, employment, education level, or marital status. We conclude that many patients were suitable for M+R, but fewer than half accepted it; this decision was unrelated to age, race, employment, or marital status.

Implications of anastomotic leakage after total gastrectomy for gastric carcinoma.

BACKGROUND/OBJECTIVES: Oesophagojejunal anastomotic leakage is a serious complication following total gastrectomy, and is reported to be decreasing in frequency. This study was an audit of the radiological and clinical frequency of such leakage and its consequences. METHODS: A retrospective (1983-2000) cohort study was undertaken in a tertiary institution where 175 patients had undergone a total gastrectomy for gastric carcinoma with oesophagojejunal reconstruction using a stapling device and a 50 cm J-loop. Anastomotic leakage was sought 3-9 days postoperatively using a Gastrograffin (diatrizoate meglumine) swallow. RESULTS: Leakage was demonstrated in 7 patients (4%), being subclinical in 2, minor in 4, and fatal in 1. There was no correlation between leakage and patient factors (age, medical risk, haemoglobin, albumin), surgical factors (surgical seniority, approach, reconstruction, splenectomy, lymph node dissection) or tumour factors (stage, nodes examined, and margin positivity). However, intraoperative difficulties or mishaps were recorded in most cases of leakage. Subclinical leakage was marked by an uneventful postoperative course, and low-volume enterocutaneous fistulas were self-limiting. One patient developed a subphrenic abscess that required drainage. One patient suffered an intrathoracic leak which proved fatal. CONCLUSIONS: Anastomotic leakage was an infrequent complication of total gastrectomy when using a stapling device and a 50 cm J-loop. It was related to intraoperative surgical difficulty and mishap rather than conventional patient and tumour factors. It was subclinical or self-limiting, if occurring in the abdomen, but fatal if in the chest.

Breast cancer screening in developing countries.

Diagnosing breast cancer early and efficiently is a critical component of any strategy aimed at decreasing breast cancer mortality in developing countries. In this chapter, I evaluate the evidence behind screening strategies and its controversies. The effect of breast-cancer screening has never been formally evaluated in developing countries, and data from the major screening trials need to be viewed in this context. Screening asymptomatic women by means of breast self-examination, clinical examination or mammography can play a significant role in decreasing breast-cancer mortality in developing countries. Major programmes should not be implemented, however, until adequate diagnostic and therapeutic facilities are in place. The most fundamental interventions in early detection, diagnosis, surgery, radiation therapy, and drug therapy must be integrated, organised and resourced appropriately within existing healthcare structures.

A 40-50kDa Glycoprotein Associated with Mucus is Identified as α-1-Acid Glycoprotein in Carcinoma of the Stomach.

BACKGROUND AND AIM: Secreted gastric mucins are large O-glycosylated proteins of crude mucus gels which are aberrantly expressed in malignancy. An albumin associated 55-65kDa glycoprotein was previously shown in mucus gels in gastric cancer. The aim of this study was to investigate its expression and identification in human gastric tissue. METHODS: Mucins were purified from crude mucus scrapings of 16 partial and 11 total resections and a rabbit polyclonal antibody was raised to the 55-65kDa glycoprotein. The location and expression of the glycoprotein was examined in normal gastric mucosa (n=20), intestinal metaplasia (n=18) and gastric cancer (n=27) tissue by immunohistochemistry. Mucins were analyzed by isoelectric focusing (IEF) on 2-D polyacrylamide gels. Identification of the 40-50kDa glycoprotein was by MALDI-TOF MS technique. Plasma levels were examined by Western blotting. RESULTS: Extensive SDS-PAGE analysis gave a PAS positive glycoprotein in the 40-50kDa range, in patients with gastric cancer but not normals. It was expressed in parietal and columnar cells of normal gastric tissue and intestinal metaplasia respectively, and in 22 of 27 gastric cancer specimens. In 2-D PAGE stained with Coomassie Blue there were 3 spots positively identified as alpha-1-acid glycoprotein (AGP) by MALDI-TOF MS technique. PAS staining revealed a single bright spot in the same position but could not be identified. Preliminary measurements showed slightly higher levels of AGP in plasma of patients with gastric carcinoma. CONCLUSION: AGP levels are increased in gastric tissue and in the plasma of those with carcinoma of the stomach.