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Biomedical subjects

S S Somers

Publications and source records attributed to S S Somers.

At least 19 recordsLinked to original sources
PubMed2005

Cost-effective laparoscopic TEP inguinal hernia repair: the Portsmouth technique.

NICE (UK) has not recommended unilateral primary laparoscopic inguinal hernia repair because of its expense. A two-port technique without balloon inflator or routine tacking was developed, which helped reduce costs to just Pounds 35 more than day-case open hernia repair. Over a 6-month period, 40 patients underwent 60 TEP repairs with a 6-month follow up. Zero degree laparoscope (10 mm) and blunt graspers (5 mm) created the pre-peritoneal space, identified landmarks and completed the dissection. Trimmed 15 x 15 cm mesh was placed over each defect. Operating times for unilateral and bilateral hernias for consultants and supervised trainees were 30*, 42.5* and 40*, 55* min (*: Median) respectively. Verbal rating pain scores at 24 and 72 h were 1* (0-3) and 0* (0-2) respectively. Patients returned to activity, driving and work in 5*, 7* and 14* days respectively. Cost of laparoscopic hernia repair was calculated at Pounds 105. A two-port laparoscopic hernia repair can be performed effectively and safely, in reasonable time and at a low cost. These data support the use of this technique in primary unilateral inguinal hernia.

Adult↗
PubMed2004

Implementation of a specialist-led service for the management of acute gallstone disease.

BACKGROUND: The 'gold standard' treatment for acute cholecystitis and biliary colic requiring hospital admission is urgent laparoscopic cholecystectomy. This is not routinely available in all hospitals. METHODS: A retrospective audit of emergency admissions with acute cholecystitis or biliary colic from January to December 2000 led to the development and implementation of a specialist-led protocol for the urgent management of acute gallstone disease. A second audit was carried out covering the 6 months after implementation. RESULTS: One hundred and fifty-eight patients were admitted with acute cholecystitis or biliary colic in the first audit period and 110 in the second interval. The rate of cholecystectomy at index admission increased from 37.3 to 67.3 per cent, at a median of 3 days after admission, and the conversion rate to open surgery fell from 32 to 12 per cent. Median hospital stay fell from 9 to 5.5 days, and the unplanned readmission rate decreased from 19.0 to 3.6 per cent. CONCLUSION: Urgent cholecystectomy for the management of acute gallstone disease is feasible and achievable in an acute services hospital with a specialist upper gastrointestinal team. It can lead to a reduced conversion rate, shorter hospital stay, fewer unplanned readmissions, an acceptable operating time and a low complication rate. The protocol is recommended for implementation in other hospitals.

Acute Disease↗
PubMed2004

Timing of urgent laparoscopic cholecystectomy does not influence conversion rate.

BACKGROUND: The optimal treatment of acute gallstone disease is urgent laparoscopic cholecystectomy, but there is confusion about the effect of delay in operation on conversion rates. Most reports suggest that delay beyond 3 or 4 days leads to a higher conversion rate. This study assessed the conversion rate in relation to the timing of laparoscopic surgery. METHODS: This institution operates a specialist-led protocol for the urgent management of all admissions with acute gallstone disease. Data were collected prospectively over 6 months. RESULTS: Between March and August 2002, 84 patients with acute gallstone disease underwent urgent laparoscopic cholecystectomy at the index admission with an overall conversion rate of 12 per cent. Four of 40 procedures carried out within 3 days of admission were converted, compared with six of 44 after 3 days. Five of 46 carried out within 4 days of admission were converted, compared with five of 38 after 4 days. There were no deaths and one common bile duct injury. CONCLUSION: As long as the procedure is carried out by experienced upper gastrointestinal surgeons working within a specialist-led protocol, the conversion rate for laparoscopic cholecystectomy can be as low as 12 per cent. The timing of urgent laparoscopic cholecystectomy has no impact on the conversion rate.

Adult↗
PubMed1998

Laparoscopic-assisted vs. open surgery for colorectal cancer: comparative study of immune effects.

PURPOSE: Our aim was to test the hypothesis that laparoscopic-assisted resection for colorectal cancer has an immunologic advantage over traditional open surgery. METHODS: Sixteen patients with colorectal cancer were randomized to undergo laparoscopic-assisted resection or open surgery. Basic patient data were recorded, and serum interleukin-6 levels, relative proportions of lymphocytes, and human leukocyte antigen-DR expression on monocytes were determined at specific time intervals. RESULTS: Operating time was longer for laparoscopic-assisted resection (P=0.02), but analgesic requirements were less (P=0.04). All patients exhibited the following: interleukin-6 levels increased to a maximum at 4 hours and returned to preoperative levels within 48 hours. This response appeared greater for open resection (mean peak level, 313 vs. 173 pg/ml; P=0.25). Relative granulocytosis (P < 0.001) was seen within 48 hours, which was offset by a decrease in percentage of lymphocytes (P < 0.001). Changes in lymphocyte subfractions were most significant seven days postsurgery: natural killer cells decreased (P=0.003); T cells increased (P=0.008), with elevation in the CD4/CD8 ratio (P=0.003). B cells were largely unchanged at all time periods. Human leukocyte antigen-DR expression on monocytes was significantly less at 48 hours postsurgery (P < 0.001). All changes were reversed within three weeks of surgery. There were no differences when comparing laparoscopic-assisted resection with open surgery. CONCLUSIONS: Both laparoscopic-assisted resection and open surgery affect the immune response. It would appear that laparoscopic-assisted resection does not have an immunologic advantage over open surgery in patients with colorectal cancer.

Adult↗
PubMed1996

Surgical implications of tumour immunology.

The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient.

Combined Modality Therapy↗
PubMed1995

Manipulation of local and systemic host defence in the prevention of perioperative sepsis.

This review addresses some of the immunological issues surrounding the complex problem of perioperative sepsis. It identifies an immunological paradox between the relative immunosuppression of the immediate postoperative period and the relative immune activation of established sepsis, in addition to discussing current knowledge of the mechanisms surrounding these phenomena. Much remains unknown about perioperative immunoregulation; there are a number of potential mechanisms, however, whereby local and systemic immune defences can be modified or enhanced. Provided patients at risk can be identified, such manipulations may find application in preventing infection and sepsis after surgery.

Humans↗
PubMed1993

Inhibition of interleukin-2 dependent immune responses by serum from patients with advanced gastrointestinal cancer.

Immunotherapy with high-dose interleukin-2 (IL-2) fails to induce clinical responses in patients with advanced gastrointestinal cancer, but may be effective in patients with malignant melanoma or renal adenocarcinoma. The hypothesis that this failure may be related to immunosuppressive moieties present in patients with advanced gastrointestinal cancer was investigated. Serum samples from 93 patients (32 advanced gastrointestinal cancer, 22 localized gastrointestinal cancer, 13 melanoma/renal adenocarcinoma and 26 age-matched controls) were incubated with peripheral blood lymphocytes from healthy volunteers. The generation of cytolytic lymphokine-activated killer (LAK) cells and the allogeneic mixed lymphocyte response (MLR) were measured in-vitro. LAK effector cytotoxicity (mean % +/- SEM) was significantly (P < 0.05) decreased by serum from advanced gastrointestinal cancer patients (30 +/- 3) compared with that from controls (47 +/- 3), serum from patients with localized gastrointestinal cancer (49 +/- 2) or that from patients with melanoma or renal adenocarcinoma (51 +/- 2). MLR responses were also significantly (P < 0.05) decreased using advanced gastrointestinal cancer patients serum compared to controls. A dose-response phenomenon for suppression of MLR was observed. Serum from patients with melanoma or renal adenocarcinoma was not significantly different to control samples. The immunosuppressive properties of serum from patients with advanced gastrointestinal carcinoma may abrogate therapeutic attempts using IL-2.

Aged↗
PubMed1993

Isolation and expansion of lymphocytes from gastrointestinal tumour tissue.

Adoptive cellular immunotherapy (ACI) with tumour-infiltrating lymphocytes (TIL) has met with some success in patients suffering from malignant melanoma. However, the success of this approach hinges on the successful isolation and in vitro expansion of TIL. Viable, IL-2 responsive TIL were obtained from only two of five gastrointestinal primary or 'non-lymph node' secondary gastrointestinal tumours. In contrast, proliferating TIL were successfully expanded from four out of five lymph node secondary deposits from gastrointestinal cancer patients, but these TIL were non-cytolytic. Conversely, proliferating lymphocytes were generated from six out of seven malignant effusions from gastrointestinal cancer patients in the late phase of their disease. Despite the presence of effective anti-tumour cytotoxic activity in one such culture, these lymphocytes failed to proliferate sufficiently for potential clinical use. Consequent upon these findings, we are sceptical that ACI using mononuclear cells infiltrating primary or secondary sites from patients with gastrointestinal cancer will be feasible.

Aged↗
PubMed1992

Multifocal neurotoxicity during interleukin-2 therapy for malignant melanoma.

A 43-year-old female with metastatic melanoma was treated with a combination chemoimmunotherapeutic regimen of DTIC with interleukin-2. Three days after cessation of her interleukin-2 she developed a rapid onset quadriparesis. Computed tomographic scanning failed to show any intracranial pathology but magnetic resonance imaging demonstrated the presence of multiple foci of cellular infiltration. The patient gradually recovered both clinically and radiologically over the following three months. The nature of these infiltrative foci remains uncertain; however, they are unlikely to have been of neoplastic origin and may be due to interleukin-2-induced lymphocytic infiltration. Whenever possible, we suggest that assessment of cerebral involvement with metastatic disease in these patients be by magnetic resonance if initial computed tomography is negative.

Adult↗
PubMed1991

Simplified quantitation of cytotoxicity by integration of specific lysis against effector cell concentration at a constant target cell concentration and measuring the area under the curve.

Experience with the lytic unit (LU) as a measure of cytolytic efficiency has indicated that its accuracy is limited, even if expressed in a logarithmic format. A new method of quantifying cytotoxicity from effector dilution assays is proposed: the area under the curve (AUC) of the Ig (E/T) ratio vs. percentage cytotoxicity plot, gives an overall measure of lytic efficiency. The AUC derived from the Briggs-Haldane kinetic model is dependent on both the kinetic parameters that determine the efficiency of effector cells (the Michaelis constant KM and the catalytic constant kcat). AUC provides an index of inhibition or stimulation of lysis, independent of whether the modulation is kinetically competitive, uncompetitive or the same AUC value. In practice the method may be applied to interpret simple cytotoxicity assay data, where effector cells are being used in standardised screening for modifiers of the cytolytic response. Illustrative data of LAK cytotoxicity influenced by dose of the LAK response modifiers IL-2, TGF beta, TDSF and 5-FU, show different relationships between lytic units, KM and AUC. These data also show a wide range in the Hill coefficient and would be consistent with a cooperative effect dependent on the effector cell efficacy. This confirms that using LU as a simple measure of cytolytic efficiency could be erroneous and suggest that cytolytic response modifiers can produce a variety of kinetic changes. The AUC method, however, provides a comparative measure of efficiency in these situations, independent of mechanism.

Cytotoxicity Tests, Immunologic↗
PubMed1991

Effects of different lipid emulsions on lymphocyte function during total parenteral nutrition.

A prospective randomized study of the immunological effects of three total parenteral nutrition (TPN) regimens in patients undergoing preoperative parenteral nutrition was conducted. In one regimen the calories were derived solely from glucose. The others were identical except that 50 per cent of the calories were provided as lipid emulsion, in one as long-chain triglycerides (LCT) only while the other contained half the fat as medium-chain triglycerides (MCT) and half as LCT (MCT/LCT). Natural killer (NK) activity and lymphokine-activated killer (LAK) activity were significantly higher after TPN with the MCT/LCT solution. A significant fall in LAK activity occurred after TPN with the LCT solution. The interleukin 2 content in supernatants from activated T lymphocytes was significantly higher after TPN with the LCT-containing solution. Solutions containing LCT and those containing MCT perturb cytokine interactions, but this is less with MCT-containing solutions, which may augment certain responses. These observations may have implications for the design of TPN regimens.

Aged↗
PubMed1991

Comparison of transforming growth factor beta and a human tumour-derived suppressor factor.

Serum-free supernatants from the human melanoma cell line G361 contain a factor that can potently suppress the generation of tumouricidal lymphokine-activated killer (LAK) cells in response to interleukin-2. To characterise the suppressive factor of tumour origin we performed a number of physicochemical and functional comparisons with another immunosuppressive protein, transforming growth factor beta (TGF beta). The bioactivity of tumour-derived suppressor factor (TDSF), assayed by suppression of LAK cell generation, was unaffected by a reducing agent but lost when denatured with a chaotropic agent. In contrast, TGF beta was inactivated by reduction but not denaturation. TDSF lost bioactivity in conditions of pH less than 4, whereas TGF beta showed no loss of activity. The TDSF moiety has an estimated pI of 4.3 and a molecular mass of 69-87 kDa. This differs from published values of pI 9.5, and 25 kDa molecular mass for TGF beta. Anti-TGF beta antiserum reversed the effects of TGF beta but did not affect the suppression of LAK cell generation caused by TDSF. These findings provide compelling evidence that the TDSF moiety is not TGF beta, and may be a novel immunoregulatory cytokine.

Humans↗