Outcomes following major emergency gastric surgery: the importance of specialist surgeons.

BACKGROUND: The increasing subspecialisation of general surgeons in their elective work may result in problems for the provision of expert care for emergency cases. There is very little evidence of the impact of subspecialism on outcomes following emergency major upper gastrointestinal surgery. This prospective study investigated whether elective subspecialism of general surgeon is associated with a difference in outcome following major emergency gastric surgery. METHODS: Between February 1994 and June 2010, the data from all emergency major gastric procedures (defined as patients who underwent laparotomy within 12 hours of referral to the surgical service for bleeding gastroduodenal ulcer and/or undergoing major gastric resection) was prospectively recorded. The sub-specialty interest of operating surgeon was noted and related to post-operative outcomes. RESULTS: Over the study period, a total of 63 major gastric procedures were performed of which 23 (37%) were performed by specialist upper gastrointestinal (UGI) consultants. Surgery performed by a specialist UGI surgeon was associated with a significantly lower surgical complication (4% vs. 28% of cases; p=0.04) and in-patient mortality rate (22% vs. 50%; p=0.03). CONCLUSIONS: Major emergency gastric surgery has significantly better clinical outcomes when performed by a specialist UGI surgeon. These results have important implications for provision of an emergency general surgical service.

Long term outcomes following emergency intensive care readmission after elective oesophagectomy.

OBJECTIVE: The purpose of this study was to analyse the outcomes of patients readmitted to ICU following initial recovery after oesophagectomy. BACKGROUND: Surgery for oesophageal cancer has significant morbidity and poor long-term outcomes. There is limited evidence concerning the long-term outcomes of patients who require readmission to the intensive care unit (ICU) after an initial recovery following resection. METHOD: The case notes of 221 patients who underwent elective oesophagectomy over an eleven-year period were reviewed. Patients who were readmitted to ICU following initial recovery were identified and the clinical and demographic characteristics of these patients were prospectively recorded and their outcomes analysed. RESULTS: A total of 43 patients were readmitted to ICU during the study period mainly for respiratory complications or anastomotic leaks. 17 patients (40%) required a period of mechanical ventilation; 16 patients (37%) required inotropes and 2 patients (5%) required renal support. The mean ICU stay on readmission was 8 days (range 0-49 days) with an in-hospital mortality rate of 33%. In terms of long-term outcomes, the actuarial two- and five-year survival rates were 42.3 +/- 7.7% and 36.7 +/- 8.5% respectively. Multivariate analysis identified both age (Hazard ratio: 1.05 +/- 0.02; p = 0.04) and requirement for renal support (Hazard ratio: 5.63 +/- 0.8; p = 0.03) as independent adverse predictors of survival. CONCLUSIONS: Although ICU readmission following elective oesophagectomy is associated with significant mortality, the overall long-term survival rate for these patients, particularly those who do not require renal support is encouraging.

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.

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.

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.

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.

Paradoxical clinical deterioration despite near-complete pathological response to neoadjuvant chemotherapy for locally advanced gastro-oesophageal adenocarcinoma.

Neoadjuvant chemotherapy for proximal gastric cancer has shown promise in early clinical trials. We report on a clinical deterioration, yet near-complete pathological and radiological response to a combination of cisplatin and fluorouracil in a patient with locally-advanced gastric adenocarcinoma.

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.

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.

Mercedes-Benz pyloroplasty: a new technique.

Closure of large duodeno-pyloro-gastrotomy can be difficult. The resulting 'pyloroplasty' may lead to major deformity at the gastric outlet. We describe a technique that combines features of the Heineke-Mikulicz pyloroplasty and V-Y plasty. The technique is simple and is not associated with any new post-operative problem.

Esophageal adenocarcinoma developing above an Angelchik prosthesis.

The Angelchik device is a horseshoe-shaped prosthesis made of silicone elastomer; it was inserted by the trans-abdominal route to encircle the lower esophagus and was used in the treatment of gastro-esophageal reflux disease. Over 25 000 were inserted worldwide, with acceptable symptom control in between 54% and 95% of patients. However, they were associated with a wide variety of complications, including intractable dysphagia, prosthesis migration and erosion into the stomach, and a significant proportion had to be removed. This article details the cases of three patients in our institution who underwent the insertion of an Angelchik prosthesis and who subsequently developed adenocarcinoma of the esophagus. It is suggested that the Angelchik prosthesis does not effectively prevent acid reflux and thus has no effect in preventing the dysplasia-metaplasia-adenocarcinoma sequence in the lower esophagus.

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.

Paradoxical effects of 5-FU/folinic acid on lymphokine-activated killer (LAK) cell induction in patients with colorectal cancer.

The effects of treatment with 5-FU/folinic acid on interleukin-2 related lymphocyte responses was investigated in 21 patients with advanced colorectal cancer. The treatment was not suppressive of IL-2 related lymphocyte responses. Furthermore, at certain time points in the treatment cycles the capacity to generate lymphokine-activated killer (LAK) cells from the peripheral blood mononuclear cells of these patients was significantly augmented above that observed prior to treatment. These results provide a logical basis for the design of regimens which combine two approaches, each of low individual therapeutic efficacy, to treat patients with advanced colorectal cancer in the hope of increasing clinical response rates.

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.

Pneumocolon as an aid to small-bowel studies.

A prospective study was performed in 138 consecutive patients referred for small-bowel examination to evaluate the use of the pneumocolon when there was poor demonstration of the terminal ileum. One hundred and twenty-two patients were examined by enteroclysis (small-bowel enema) and 16 by small-bowel meal. Pneumocolon was used in 38 of the small-bowel enemas and in eight of the small-bowel meal examinations. In 29 cases (21 small-bowel enema; eight small-bowel meal) the use of the pneumocolon significantly improved demonstration of the terminal ileum. When the distal ileum is not adequately seen on a small-bowel study, pneumocolon serves as a useful additional technique.

Suppression of the generation of lymphokine-activated killer (LAK) cells by serum-free supernatants of in vitro maintained tumour cell lines.

Serum-free supernatants from in vitro maintained gastrointestinal cancer and melanoma cell lines inhibit the generation of lymphokine (IL-2) activated killer (LAK) cells in a time and dose-related manner. Concentrations as low as 5% can inhibit the generation of LAK cytotoxicity but inhibition of proliferation is not observed until higher concentrations are included in the culture system. Inhibition is not observed with supernatants from a breast cancer cell line nor with supernatants from normal cells. There was complete concordance between the capacity of the tumour cells themselves to inhibit LAK generation and the presence of inhibitory activity in the corresponding supernatant. The inhibitory factor(s) is stable after heating to 44 and 56 degrees C. Production of the inhibitory factor(s) is sensitive to metabolic inhibitors and has a molecular weight greater than 25 kD. The inhibition of LAK cell stimulation by tumour cells may partially explain the failure of adoptively transferred LAK cells and IL-2 therapy to cause tumour regression in man.

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.

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.