Treatment of metastatic breast cancer with liver transplantation.

Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant.

Randomized clinical trial of Ligasure versus conventional diathermy for day-case haemorrhoidectomy.

BACKGROUND: Haemorrhoidectomy is frequently associated with postoperative pain and prolonged hospital stay. A new technique of haemorrhoidectomy using the Ligasure device suited to day-case surgery is described. This technique was compared with conventional open diathermy haemorrhoidectomy. METHODS: Forty patients with grade III or IV haemorrhoids were randomized to Ligasure (group 1) or conventional diathermy (group 2) haemorrhoidectomy. Operative details were recorded and patients recorded daily pain scores on a linear analogue scale. Follow-up was at 1, 3, 6 and 12 weeks to evaluate complications, return to normal activity, ongoing symptoms and patient satisfaction. RESULTS: Reduced intraoperative blood loss (median (range) 0 (0-5) ml versus 20 (12-22) ml; P < 0.001) and a shorter operating time (10 (8-11) versus 20 (18-25) min; P < 0.001) was observed in group 1 compared with group 2. More patients in group 1 were discharged on the day of operation (18 of 20 versus 11 of 20; P < 0.05) and there was a trend towards lower postoperative pain scores on day 1 (group 1 median 5 (95 per cent confidence interval (c.i.) 2.6 to 6.8) versus group 2 7 (95 per cent c.i. 4.2 to 7.7); P = 0.36). There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications. CONCLUSION: Ligasure diathermy may be used safely in the treatment of patients with grade III or IV haemorrhoids. It reduces intraoperative blood loss and operating time, and facilitates same-day discharge.

Management of obstructing lesions of the left colon by resection, on-table lavage, and primary anastomosis.

BACKGROUND: The purpose of this study was to assess the feasibility and safety of single-stage resection, on-table lavage, and primary anastomosis in patients presenting with obstruction of the left colon. METHODS: The outcome of surgery in 73 consecutive patients presenting with obstruction of the left colon during a 5-year period was assessed in terms of perioperative complications and long-term survival. RESULTS: Sixty-three patients (86%) underwent single-stage restorative procedures. In this group there were four clinical anastomotic leaks (6%). However, there were no deaths as a result of leakage. There were four deaths (6%) but these were not due to anastomotic leakage. Long-term survival rates compared favorably, stage for stage, with large published series of elective experience. CONCLUSIONS: We believe that resection, on-table lavage, and primary anastomosis constitute the operation of choice for most patients with acute obstruction of the left colon.

Accuracy of computed tomography in predicting adrenal tumor size.

We undertook a multi-institutional, retrospective study of 51 patients with adrenal tumors (pheochromocytomas, functioning and nonfunctioning cortical adenomas, cysts and carcinomas). All patients had computed tomography (CT) with a maximum of 5 millimeter cuts the week before undergoing complete adrenalectomy. Pathologists were asked to measure the tumor to the nearest 0.1 centimeter. Tumor size obtained from pathologic reports (actual size) and CT reports (estimated size) were compared. Adrenal tumors were divided into two groups on the basis of size--tumors with actual size of 6 centimeters or greater and tumors with actual size of less than 6 centimeters. Statistical analysis was performed with Newman-Keuls analysis of variance. After controlling for tumor type and for the institution at which the measurement was made, we found that CT consistently underestimated adrenal tumor size in both tumor groups. Moreover, the average, underestimated difference for tumors 6 centimeters or greater was 32 percent, but 47 percent for tumors less than 6 centimeters (p = 0.060). CT seemed to underestimate the size of small adrenal tumors more than large tumors. Because the decision to operate on solid, nonfunctioning adrenal tumors is based on tumor size and because CT is currently the standard technique used to estimate size, our findings need to be considered before undertaking surgical treatment.

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.

Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial.

Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned.

Suture length to wound length ratio and the integrity of midline and lateral paramedian incisions.

A total of 349 patients were randomized to undergo laparotomy through a lateral paramedian incision with layered closure (n = 137), a midline incision with mass closure (n = 104) or a midline incision using layered closure (n = 108), endeavouring to close the latter two incisions with a measured suture length to wound length ratio of greater than 4:1. After 18 months follow-up, no patient in the lateral paramedian group had developed an incisional hernia whereas 7 of 104 patients undergoing a midline incision with mass closure and 7 of 108 patients undergoing a midline incision with layered closure had incisional hernias (P less than 0.01). The mean suture length to wound length ratios for the three groups were 2.6 (range 1.3-6.2), 5.0 (range 3.0-8.7) and 3.7 (range 2.0-6.3) respectively (P less than 0.0001). The lateral paramedian incision remains superior to the midline incision closed with the mass technique and its integrity is independent of the suture length to wound length ratio.

Continuous versus intermittent infusion of fat emulsions during total parenteral nutrition: clinical trial.

It is now generally accepted that fat emulsions are an efficient energy source during total parenteral nutrition (TPN). However, there is debate about how this fat should be prescribed. Some authorities prescribe fat as an intermittent infusion, alternating fat and carbohydrate, whereas others prefer a continuous infusion, giving fat simultaneously with carbohydrate. This 6-day crossover study examined the substrate-hormonal profiles of 10 patients in response to two isocaloric and isonitrogenous TPN regimens. In regimen A (intermittent), equicaloric volumes of 25% glucose and 10% Intralipid as energy sources were alternated every 12 h. During regimen B (continuous), the total nonprotein calories given each day was the same as in regimen A, but glucose and fat were infused simultaneously over every 24-h period. Amino acids were infused continuously throughout the study period in all patients. Blood samples were taken every 12 h. Wide fluctuations in insulin and all substrates occurred during regimen A. Persistent hyperinsulinemia throughout regimen A may have impaired the oxidation of exogenous fat. The substrate-hormonal profiles observed during regimen B approximated the normal postabsorptive state and were stable throughout the infusion period. The results of this study suggest that exogenous fat should be administered as a continuous infusion.

Pharmacological concentrations of lipid emulsions inhibit interleukin-2-dependent lymphocyte responses in vitro.

Most immunological functions are accomplished by means of interactions between mediator molecules (cytokines or lymphokines) and their specific receptors on the lymphocyte surface. One particular lymphokine, Interleukin-2 (IL-2) is central to the generation of most immune responses including those with antitumor activity. Prompted by two clinical trials which have suggested distinct but apparently opposite effects of lipid emulsions on the production of and lymphocyte responses to IL-2 we have examined the effects of pharmacological concentrations of three lipid emulsions currently in clinical use on IL-2 related interactions in vitro. Mitogen-stimulated and IL-2 activated human lymphocyte proliferation were both inhibited in a dose-dependent manner in the presence of all three lipid emulsions although the effects were less marked with the solution in which 50% of the calories are present as medium-chain triglycerides (MCT) rather than long-chain triglycerides (LCT). Similarly the LCT, but less so the MCT-containing solutions inhibited the generation of cytotoxic lymphokine-activated killer cells. These solutions did not inhibit the proliferation of cell lines which are not growth-factor dependent but did inhibit the growth of an IL-2-dependent cell line. We conclude that lipid emulsions can upset IL-2-dependent lymphocyte responses. These observations may lead to parenteral feeding regimens which are less immunocompromising for the tumor-bearing patient.

Effects of low dose perioperative interferon on the surgically induced suppression of antitumour immune responses.

General surgical procedures are followed by a period of generalized immunosuppression that may favour the deposition of metastases seeded at operation in patients with malignant disease. In an attempt to prevent the suppression of host-antitumour immune mechanisms following surgery we have studied the immunological effects of low-dose perioperative interferon-alpha (r-HuIFN alpha). Patients were randomly allocated pre-operatively to the control (n = 15) or treatment group (n = 15). Patients in the treatment arm received a 1-week course of subcutaneous recombinant human interferon-alpha 2a (Roferon-A) at a dose of 2 megaunits daily starting on the evening before surgery. Natural killer cell, lymphokine activated killer cell cytotoxicities and endogenous interleukin 2 production were measured 1 day before surgery and on the first, third, fifth and tenth postoperative days. Treatment with r-HuIFN alpha did not prevent the postoperative impairment of interleukin 2 production or lymphokine activated killer cell cytotoxicity. However it prevented the fall in natural killer cell activity normally observed following surgery. This may have important consequences in controlling metastatic dissemination of tumour in this vulnerable period.

Total parenteral nutrition adversely influences tumour-directed cellular cytotoxic responses in patients with gastrointestinal cancer.

The effects of total parenteral nutrition (TPN), using a lipid-based regimen, on non-specific lymphocyte function and tumour-directed cellular cytotoxicity was studied in 30 patients suffering from gastrointestinal (GI) cancer. After 7 days of TPN, augmented lymphocyte blastogenesis and production of the helper T-lymphocyte lymphokine Interleukin-2 were observed. However, over the same time period, significant impairment of basal natural killer (NK), and IL-2 activated NK activity were observed. Furthermore, lymphokine-activated killer (LAK) cell responses towards the NK resistant cell line DAUDI and the colorectal tumour cell line COLO 320, were markedly depressed. These findings have important implications for the use of this TPN regimen in GI cancer patients who might be considered for either surgical adjuvant or primary treatment with immunotherapy protocols.

Cytosolic retinoic acid binding protein in the human pancreas.

Cytosolic retinoic acid receptor in carcinoma, chronic pancreatitis, and normal pancreatic tissue were examined using sucrose density gradient centrifugation, isoelectric focussing on agarose gel and saturation analysis. Thirteen patients were studied. Cytosolic retinoic acid binding protein (cRABP) was detected in all the samples with chronic pancreatitis and pancreatic carcinoma, but not in the normal tissue. Using sucrose gradient centrifugation, the highest concentrations of cRABP were found in pancreatic carcinoma tissues, ranging from 5.5-23.9 pmol/mg protein. These concentrations were markedly different than in chronic pancreatitis tissue (0.7-2.7 pmol/mg protein). Saturation analysis of cRABP showed a mean dissociation constant of 21.5 nM and maximum binding sites of 5.2 pmol/mg protein. Cytosolic retinoic acid binding protein was separated at an isoelectric point of 4.5 on agarose gel. The presence of cRABP suggest that retinoic acid may have a role to play in the function of the pancreas.

Augmentation of lymphokine-activated killer cell activity in patients with gastrointestinal cancer.

Adoptive cellular immunotherapy with lymphokine-(interleukin 2) activated killer (LAK) cells is not as successful in patients with gastrointestinal cancer as with other tumour types. This may be because the cytotoxic capacity of LAK cells from such patients is suboptimal. In this study we have sought to augment this activity by stimulating the lymphocytes with recombinant human interferon-gamma (r-HuIFN-gamma) in addition to interleukin 2 or by depleting the lymphocytes of adherent suppressive mononuclear cells. Both procedures augment LAK activity in gastrointestinal cancer patients but adherent cell depletion results in fewer cells being available for adoptive cellular immunotherapy. No further augmentation of LAK activity of adherent cell depleted cells could be accomplished by addition of r-HuIFN-gamma. Co-stimulation of unfractionated peripheral lymphocytes with r-HuIFN-gamma is the preferable procedure for the generation of LAK cells for adoptive cellular immunotherapy in patients suffering from gastrointestinal cancer.

Lymphokine activated killer (LAK) cells in patients with gastrointestinal cancer.

Lymphokine activated killer (LAK) cells are a recently described cellular immune phenomenon with exciting potential for the treatment of tumours arising from solid organs. A comparison of some aspects of LAK cell precursors and LAK cell function was undertaken in 44 control subjects and 44 preoperative patients suffering from gastrointestinal cancer (20 localised and 24 advanced). Lymphokine activated killer cell precursor (natural killer (NK) cell) activity was significantly diminished in patients with advanced tumours (p less than 0.02) as was fully mature LAK cell activity against an NK resistant target cell (p less than 0.012). T-lymphocyte responses were not significantly different between the three groups. The reduced LAK cell generation was associated with a significantly diminished proliferative response of LAK precursors to stimulation with high dose IL-2 in vitro (p less than 0.012). Impaired LAK cell generation may explain the failure of adoptive cellular immunotherapy with LAK cells in some patients with advanced gastrointestinal cancer and prompts the search for means of augmenting this activity in such patients.

Lateral paramedian incision.

Prospective randomization of 360 patients undergoing abdominal surgery determined whether a standard lateral paramedian incision was made (group A) or one of two modifications in which the anterior sheath was incised medially and posterior sheath incised laterally (group B) or vice versa (group C), in order to determine the necessity for incising both layers laterally to provide the shutter mechanism which is held responsible for the integrity of this wound. Medial incision of the anterior rectus sheath significantly reduced the time required to perform the incision (P less than 0.02) and tended to reduce wound sepsis rate. However, this was achieved at the cost of a higher incisional hernia rate (0 per cent, 2.9 per cent and 4.6 per cent in groups A, B and C respectively, P less than 0.02). We conclude that lateral incision of both anterior and posterior rectus sheath is necessary to obviate the risk of wound hernia with the lateral paramedian incision.

Breast reconstruction by tissue expansion.

The techniques of tissue expansion for use in breast reconstruction is described, together with the results of its use in 33 patients. The advantages and disadvantages of tissue expansion in relation to other currently favoured techniques are discussed. It is concluded that tissue expansion represents a major advance in the field of breast reconstruction.