Outcome of gastric cancer surgery in elderly patients.

BACKGROUND/AIMS: The aim of the study was to review cases of gastric cancers in elderly adults (70 years of age and older), and compare demographic, clinical, pathologic features and outcomes of surgical treatment with younger patients (below 70 years of age). METHODOLOGY: The analysis included 3431 patients treated for gastric cancer between 1977 and 1998 at eight university surgical centers cooperating for the Polish Gastric Cancer Study Group (PGCSG). Patients were analyzed retrospectively according to data obtained from standardized forms and divided into two groups: group I--patients 70 years of age and over, group II--younger patients. RESULTS: There were no significant differences between these two groups in clinical symptoms at the time of diagnosis and tumor advancement. The incidence of the intestinal type according to Lauren (55.9% vs. 43.9%;p<0.05) and distally-located cancers (40.8% vs. 31.3%; p<0.05) was higher in group I. Total gastrectomies and extended lymph node dissection were performed more often in younger patients. There were no significant differences in postoperative complications between both groups, except the higher incidence of abdominal abscesses in the younger group. The overall 5-year survival was 24% and 35% for group I and II, respectively (p<0.05), and increased to 35% and 53% after radical resections, respectively. However, there were no statistically significant differences in stage-specific survival between both groups. CONCLUSIONS: Surgical resection is the method of choice in the treatment of gastric cancer. Age of the patients is not a contraindication to surgical treatment of gastric cancer.

Pentoxifylline does not affect nociception if administered postoperatively.

Proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), act as mediators of post-injury inflammation and increase pain sensitivity. Pentoxifylline (PTX) has the property of inhibiting TNF-alpha, IL-1, and IL-6 production. Previous studies revealed that the pre-injury or preoperative administration of PTX inhibited consequent hyperalgesia or postoperative pain. The aim of the study was to determine, if postoperative PTX administration affects postoperative pain. A group of 40 patients undergoing laparotomic cholecystectomy received postoperatively PTX at 10 mg/kg or placebo directly after the termination of general anesthesia. There were no differences in postoperative pain, analgesic drug requirement or TNF-alpha and IL-6 serum levels between the groups.

Melatonin precursor; L-tryptophan protects the pancreas from development of acute pancreatitis through the central site of action.

Melatonin, produced from L-tryptophan, protects the pancreas against acute damage by improving the antioxidative status of tissue. Melatonin receptors have been detected in the brain, but the contribution of these receptors to the pancreatic protection is unknown. The aim of our study was to compare the effects of melatonin precursor; L-tryptophan given intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on the course of acute pancreatitis. Acute pancreatitis was induced by subcutaneous infusion of caerulein (5 microg/kg-h x 5 h). L-tryptophan was given i.p. (2.5, 25 or 250 mg/kg) or administered into right cerebral ventricle (0.02, 0.2 or 2.0 mg/rat) 30 min prior to the start of caerulein infusion. Plasma amylase, lipase and TNF alpha activities were measured to determine the severity of caerulein-induced pancreatitis (CIP). The lipid peroxidation products: malonylodialdehyde and 4-hydroksynonenal (MDA + 4-HNE) and activity of superoxide dismutase (SOD) were measured in the pancreas of intact or CIP rats with or without L-tryptophan pretreatment. Melatonin blood level was measured by RIA. CIP was confirmed by histological examination and manifested as an edema and rises of plasma levels of amylase, lipase and TNF alpha (by 550%, 1000% and 600%). MDA + 4-HNE was increased by 600%, whereas SOD activity was reduced by 75% in the pancreas of CIP rats. All manifestations of CIP were significantly reduced by pretreatment of the rats with L-tryptophan given i.c.v. at doses of 0.2 or 2.0 mg/rat, or by peripheral administration of this amino acid used at dose of 250 mg/kg i.p. In control rats plasma level of melatonin averaged about 40 +/- 2 pg/ml and was not significantly affected by CIP, by central application of L-tryptophan (0.02, 0.2 or 2.0 mg/rat) or by peripheral administration of this melatonin precursor used at doses of 2.5 or 25 mg/kg i.p. Plasma melatonin level was markedly increased by pretreatment of the rats with L-tryptophan given i.p. at dose of 250 mg/kg. We conclude that central administration of melatonin precursor; L-tryptophan, as well as peripheral application of high dose of this melatonin precursor prevented the pancreatic damage produced by CIP. The favorable effect of peripherally administered L-tryptophan could be related to the rise of melatonin plasma level and to pancreatoprotective action of this indoleamine. The beneficial effect of centrally administered L-tryptophan could be mediated through activation of central receptors for locally produced melatonin.

[A case of acute appendicitis with abdominal actinomycosis]. / Ostre zapalenie wyrostka robaczkowego wspólistniejace z promienica brzuszna.

The authors presented a rare case of acute appendicitis with abdominal actinomycosis. Diagnostic and therapeutic procedures for accidentally found abdominal actinomycosis were discussed based on current literature.

[Hemangiopericytoma localized in the peritoneum]. / Haemangiopericytoma o wewnatrzotrzewnowej lokalizacji.

The authors present a rare case of intraperitoneal haemangiopericytoma. Diagnostic and therapeutic procedures were discussed based on current literature.

[Results of kidney transplantation in Krakow in 1992-2000]. / Wyniki przeszczepiania nerek w Krakowie w latach 1992-2000.

The aim of the study was an analysis of renal transplantation results in the Krakow Transplant Center during 1992-2000. The analysis concerned 94 cadaveric transplant recipients. The study group included 31 females aged 23 to 61 years (mean 40.4 years) and 63 males aged 16 to 60 years (mean 41.8 years). The time of pre-transplant renal replacement therapy ranged from 4 to 120 months (mean 32 months). The mean time of total ischaemia was 22 hours 20 minutes. The majority of the recipients had three identical antigens out of six typed. Most of the recipients were treated with three immunosuppressive drugs including: Cyclosporine A, Azathioprine and steroids. Immediately after kidney transplantation 25.6% of the patients had urine output and did not require dialysis. Acute renal failure (ARF) of the graft was observed in 73.2% recipients. The average number of hemodialysis sessions in patients presenting ARF was 10. Acute rejection was diagnosed in 41.5% of the patients. The most frequent complications were: CMV (cytomegalovirus) infection, UTI (urinary tract infection) and policytemia. In the study group 1-year survival rate of the patients was 97.8% and 1-year graft survival was 93.61%. The 5-year survival rates both in the patients and the grafts were very satisfactory (96.96% and 87.7% respectively).

Tumour-cell-induced production of tumour necrosis factor by monocytes of gastric cancer patients receiving BCG immunotherapy.

Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor alpha (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.

[Low serum cholesterol level and the risk of cancer of the colon]. / Male stezenie cholesterolu w surowicy a zagrozenie rakiem jelita grubego.

The study aimed at assessing a degree of low serum cholesterol relationship to carcinoma of the colon. The study involved 137 patients with carcinoma of the colon and 54 patients serving as a control group. Serum cholesterol and total proteins levels were assayed and nutritional status of the patients was analysed. It was found that serum cholesterol was significantly lower in patients with both advanced and mild cancer of the colon in comparison with a control group. Similar tendency was noted in the group of female patients with cancer of the colon but the difference between the patients with not advanced cancer and control group was statistically insignificant. Serum total proteins did not differ in patients with cancer of the colon and control group. In the group of male patients (with both stages of the cancer) in whom low serum cholesterol was noted (below 5.2 mM/L) a risk of cancer was 3-7 times higher. In female patients relative risk of cancer was significantly higher only in the advanced stages of the disease.

Postoperative immunochemotherapy (BCG + 5-FU) in advanced gastric cancer.

Three hundred and twenty-two patients with locally advanced (stages III and IVA) and disseminated (stage IVB) gastric cancer were included in a randomized trial to assess the effect of immunochemotherapy (BCG and 5-fluorouracil,5-FU). The survival of patients receiving chemoimmunotherapy was compared to chemotherapy (5-FU) or no further treatment (control) groups. Patients with stage III underwent radical surgery (subtotal or total resection), stage IVA palliative resection, while explorative laparotomy or bypass was performed in stage IVB. Patients with stage III and IVA receiving immunochemotherapy had significantly (p less than 0.05) prolonged survival in comparison to chemotherapy or control groups. Prolongation of survival was more pronounced in patients with diffuse type carcinoma than in patients with intestinal type of tumour according to Lauren's classification. The survival of patients receiving chemotherapy was somewhat shorter than that of the control group, but the differences were not statistically significant. There was no effect of either immunochemotherapy or chemotherapy in patients with stage IVB. No serious side effects of immunochemotherapy were noted. These results indicate that immunochemotherapy may be a safe form of adjuvant treatment in patients with operable gastric cancer.

The altered expression of MHC-class II determinants on monocytes of cancer patients.

The expression of MHC class II determinants Ia.7 (detected by cross reactive mouse anti-Iak antibody) and HLA-DR on monocytes (MO) of gastric and colorectal cancer patients was examined. An increased proportion of MO bearing the Ia.7 determinant was found, while the number of MO expressing DR was not elevated. In gastric cancer patients the increased expression of the Ia.7 determinant was most pronounced in advanced cancer (stage IVA and IVB). The increased expression of this determinant was related to the presence of the tumour as the number of MO expressing Ia.7 decreased 6 months following surgical resection of the tumour. Further, the increased expression of Ia.7 on MO correlated with the tumour infiltration of the serosa. The Ia.7 determinants were mainly expressed on MO which also expressed the receptor for the Fc part of immunoglobulin. Immunostaining in cellular infiltrates surrounding the tumour revealed that Ia.7+ macrophages (MO) were more numerous than in normal gastric mucosa and severe chronic gastritis and were mostly present in close proximity to tumour cells, while DR+MO were mainly localized within the stromal tissue of the tumour and their number was not increased in cancer infiltrates. These observations indicate that the Ia.7+ subpopulation of MO may be involved in the anti-tumour response of the host.

Serial immunological testing in patients with gastric cancer.

Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations Ta and T29o was unchanged except depression of T29o in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU + BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.

Suppressor cells and survival of patients with advanced gastric cancer.

The association of suppressor cells with survival of patients with gastric cancer was investigated. Phytohemagglutinin (PHA)-induced lymphocyte response and the presence of nonspecific suppressor cells were assessed in patients with different stages of gastric cancer. The presence of suppressor cells was determined by their ability to inhibit the PHA response of normal peripheral blood mononuclear leukocytes. Depression of the PHA response was related to the stage of disease and was also associated with the presence of suppressor cells. Of 245 patients tested, 76 (31%) had suppressor cells. Adherent, nonspecific esterase-positive cells (presumably, monocytes) accounted for the suppression in most cancer patients. The occurrence of suppressor cells and the tumor load were related because the incidence of detectable suppressor cells decreased after surgery in patients with resectable tumor but increased in patients undergoing palliative surgery. In patients with advanced disease who had a generally poor prognosis, the occurrence of suppressor cells was associated with a significantly increased survival. Hence the common view that a depressed lymphocyte response correlates with a poor clinical outcome may not be valid in all types of cancer.

"Activated" monocytes in gastric cancer patients. I. Increased Fc receptor expression, antibody-dependent cellular cytotoxicity and NBT reduction.

The Fc receptor expression, antibody-dependent cellular cytotoxicity (ADCC), and nitro-blue tetrazolium (NBT) reduction of peripheral blood monocytes from 150 patients with different stages of gastric cancer was assessed and compared with results obtained in 77 normal persons and 104 patients with non-malignant diseases of the gut. Monocytes of cancer patients showed an increased ability to form rosettes with human 0, Rh + erythrocytes coated with D-specific antibody. ADCC and NBT reduction were also elevated but no correlation was found with the stage of disease. However, all these phenomena were related to the tumor load as elevated values were the same 4-6 months after surgery in the unresectable-tumor group, while they decreased in patients with resectable tumors. These observations suggest that monocytes of some cancer patients are functionally altered ("activated") in the course of disease.

"Activated" monocytes in gastric cancer patients. II. Suppressor and cytostatic activity in vitro.

The spontaneous nitro-blue tetrazolium (NBT) reduction of monocytes from patients with gastric cancer was assessed and compared with an in vitro monocyte-mediated cytostasis of tumor cell lines and their suppressor activity. The increased NBT reduction correlated with the ability of monocytes to inhibit mitogen-induced normal lymphocyte response and cytostatic activity against L-1210 murine lymphoma cell line. These observations suggest that "activated" monocytes of some cancer patients may play the role of suppressor cells and exert an anti-tumor effect in vitro.

Cytostatic activity on tumour cells of monocytes from patients with gastrointestinal cancer.

The ability of monocytes from patients with gastrointestinal cancer to inhibit tumour cell growth and suppress PHA-induced lymphocyte response in vitro was assessed. Isolated monocytes, i.e., adherent Fc+ cells from mononuclear cell suspension, were cytostatic but not cytolytic for both K562 line and L1210 lymphoma cells. Monocytes from the patients showed an increased ability to inhibit the growth of L1210 but not K562 line cells. The increased cytostatic activity of monocytes was associated with their suppressor activity. This suggests that suppressor monocytes are also able to arrest tumour cell growth in vitro.