[Restoration of the continuity of the colon with preservation of an existing colostomy]. / Erhaltung einer vorbestehenden Kolostomie bei Re-Operation des Dickdarms - Ein technischer Hinweis.

A new technique for the restoration of the continuity of the colon with preservation of an existing colostomy is described here. A 75-year-old male with a three-year history of abdominal-perineal resection and a well functioning end colostomy was admitted to our department for a second primary cancer of the descending colon. At operation the colon was divided close to the abdominal wall; the colostomy was left in situ while the descending colon and mesocolon were radically resected. The viability of the colostomy was being continuously inspected. An EEA stapler was then inserted through the colostomy and an anastomosis was created. Shortening the length of the operation and avoiding the possible complications that follow the creation of a new stoma are the major benefits of the technique. Still, the viability of the colostomy after its separation of the rest of the colon and mesocolon has to be ensured before proceeding.

Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience.

We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in ovarian cancer patients treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A total of 240 patients, who had never been exposed to platinum compounds previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n = 136) intravenously, and intraperitoneal carboplatin plus intravenous cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range 3-12) and 5 (range 4-6) for the intravenous and intraperitoneal treatment regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous carboplatin treatment developed symptoms compatible with a hypersensitivity reaction to carboplatin, that was always verified by manifestation of at least similar symptoms on rechallenging. In contrast, in the group of 46 patients on intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever noticed. Hypersensitivity reactions always occurred after administration of the first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients, which manifested as itching (20 patients) and small area erythema plus erythema of the palms and soles (12 patients), occurring either during intravenous injection when most of the drug scheduled had been administered, or within 3 days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely as itching, diffuse erythroderma, rigor, facial swelling, throat and chest tightness, tachycardia (12 patients) and bronchospasm (2 patients), and hypertension or hypotension in 8 and 4 patients, respectively. With appropriate symptomatic management, discontinuation of carboplatin treatment was not required in patients with mild hypersensitivity reactions, but none of the 12 patients with severe reactions was able to receive a full subsequent dose of carboplatin on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by cisplatin, which was given for 4-6 courses without side effects. These findings indicate that although hypersensitivity reactions are common in general, occurring in almost 1 of every 6 patients treated intravenously with carboplatin, their clinical picture is variable, leading to discontinuation of treatment in only 6% of patients. This is not the case when the intraperitoneal route of carboplatin administration is used when indicated.

Extravesical foreign body presenting as a bladder tumor.

Although foreign bodies left in the abdominal cavity may remain asymptomatic for long periods, they may also cause serious complications. We present a case of gauze forgotten in the lower abdomen which remained asymptomatic for almost 1 year. When a granuloma had formed, it infiltrated the bladder wall giving the clinical and imaging appearance of an invasive bladder tumor.

A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.

Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3-4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter 2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5-84.0) of the IV group and in 33/44 = 75% (95/CI 59.7-86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8-62+) for the IV group and 18 (6-72+) for the IP group. Median survivals were: 25 months (6-80+) and 26 months (6-72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0. 01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950-1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.

Second-line chemotherapy with cisplatin-ifosfamide in patients with ovarian cancer previously treated with carboplatin-cyclophosphamide.

In an effort to use antineoplastic drug combinations which are active in platinum resistant ovarian cancer or which can induce a second response after a platinum first-line treatment, we conducted a study on 30 ovarian cancer patients previously treated with carboplatin plus cyclophosphamide who were given ifosfamide 5 g/m2 i.v. divided over days 1 to 3 plus mesma combined with cisplatin 100 mg/m2 i.v. divided over days 1 to 3 every 4 weeks as second-line treatment. Eight patients had never entered remission with first-line chemotherapy while 22 patients had tumor recurrence within 6 to 18 months after the end of chemotherapy and their tumors were considered potentially platinum sensitive. Responding patients received 6 courses while palliative treatment for nonresponders was provided. Of the 22 patients with tumor recurrence, 8 patients responded with one partial response (PR) and 7 complete clinical responses (CCR). Two out of the 8 patients with platinum resistant disease demonstrated short lasting PR. Seven patients with CCR underwent second-look operation and in two a pathological CR was documented. Median time to progression was 6 mo (4-12). The median overall survival was 12 mo (4-20). Myelotoxicity despite G-CSF administration was significant with grade 4 leukopenia in 40% and grade 3 thrombocytopenia in 20% of patients. Central nervous system (CNS) toxicity was significant with 30% somnolence, 20% disorientation and an episode of grand-mal epilepsy ascribed to ifosfamide. With a 33% response rate the combination is as effective as new agents employed in relapsed ovarian cancer. Platinum-refractory disease may respond to a lesser degree. The most important determinant of response was the progression-free interval from first-line chemotherapy. Whether patients recurring after carboplatin plus cyclophosphamide have a greater chance to respond to cisplatin plus ifosfamide or vice-versa cannot be supported by the current data and therefore randomized studies should be performed to this end.

Expression patterns of the novel catenin p120cas in gastrointestinal cancers.

p120cas is involved in signal transduction upon src or growth factor stimulation as well as in E-cadherin mediated cell adhesion and may play an important role in carcinogenesis. In this study, we evaluated immunohistochemically the expression and cellular localization of p120cas in 40 gastric, 43 colorectal and 20 pancreatic carcinomas, and examined the relationship between p120cas expression and pathological features. Altered p120cas expression was observed in 70%, 65% and 60% of gastric, colorectal and pancreatic cancers, respectively. The most common abnormality was of cytoplasmic expression associated with loss of membranous distribution found in 37% of gastric, in 25% of colorectal and in 25% of pancreatic cancers. Heterogeneous staining was noted in 15%, 19% and 20%, and complete loss of expression in 18%, 21% and 15% of gastric, colorectal and pancreatic cancers, respectively. There was no correlation between p120cas staining pattern and tumour grade or stage. Aberrant expression of p120cas which may reflect changes in signal transduction pathways occurs frequently in human malignancies.

Aberrant E-cadherin expression associated with loss of differentiation and advanced stage in human pancreatic cancer.

E-cadherin is a cell-cell adhesion molecule involved in tumour invasion and metastasis. We evaluated E-cadherin expression immunohistochemically in 43 formalin-fixed, paraffin-embedded specimens of pancreatic cancer and investigated its relationship to histopathological features. In non-cancerous pancreatic cells E-cadherin immunoreactivity was localized at the cell membrane, particularly at the intercellular junctions. Abnormal E-cadherin expression was found in 18 (42%) cases. A significantly higher proportion of poorly-differentiated tumours (71%) showed abnormal E-cadherin expression compared with moderately (50%) and well (19%) differentiated tumours (P = 0.037). There was a significant correlation between abnormal E-cadherin expression and lymph node involvement (P = 0.013), the presence of distant metastases (P = 0.034) and advanced tumour stage (P = 0.025). These findings suggest that loss of normal E-cadherin expression is involved in the progression of pancreatic cancer.

Biochemical modulation of fluorouracil: comparison of methotrexate, folinic acid, and fluorouracil versus folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial.

Recent advances in biochemical pharmacology have revealed the basis for the biological modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and folinic acid (FA). Sequential use of MTX given 24 h prior to 5-FU has resulted in enhanced cell kill in vitro and in vivo. In addition, administration of FA prior to 5-FU has led to potentiation of 5-FU action by stabilization of the ternary complex of thymidine synthase. In the present randomized study, two groups of patients with advanced colorectal cancer were treated as follows: 43 patients (pts) in group A received 5-FU + FA, whereas 45 pts in group B received 5-FU + FA + MTX. The dosage was as follows: group A received FA i.v. at 300 mg/m2 per day, prior to i.v. 5-FU at 500 mg/m2 per day on days 1-4; group B was given MTX i.v. at 130 mg/m2 per day on day 0, followed 24 h later by FA at 15 mg q6h x 6, and 5-FU + FA was started on day 1 and given at the same doses and schedule described for group A. Objective responses were achieved by 8/43 pts in group A (1 complete response and 7 partial responses) and by 18/45 pts in group B (3 complete and 15 partial responses), all occurring in the liver. There was no significant difference in the median time to progression (group A 6.1 months, group B 6.8 months) or the median survival (group A 9.2 months, group B 10.3 months). Toxicity was significantly greater in group B [grade 2-3 mucositis 20% versus only 2% in group A (P < 0.0001); grade 3 diarrhea in group B 15% versus 3% in group A (P < 0.001)]. According to our results, double biological modulation of 5-FU with MTX + FA led to an enhanced response rate with increased toxicity as compared with the 5-FU + FA regimen given at less than its maximally tolerated dose.

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6-hydroxydopamine (6-OHDA) causes selective acute degeneration of the adrenergic nerve terminals--that is, a reversible chemical sympathectomy. The effect of this drug was studied on the insulin-stimulated gastric secretion. Insulin-stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after 6-OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibers in the vagus nerve might have some modulating effect on the insulin-induced gastrin release.

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6 hydroxydopamine (6 OHDA) causes selective acute degeneration of the adrenergic nerve terminals, that is a reversible chemical sympathectomy. The effect of this drug was studied on the insulin stimulated gastric secretion. Insulin stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin was measured before and after 6 OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations, that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibres in the vagus nerve might have some moduling effect on the insulin induced gastrin release.

The effect of propranolol on insulin-stimulated gastric secretion in dogs.

The effect of beta-adrenergic blockade on the insulin hypoglycemia-induced gastric secretion was studied. Insulin-stimulated (0.15 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after beta-adrenergic blockade with propranolol (20 microgram/kg/min intravenous infusion) in gastric fistula and Heidenhain pouch dogs. Insulin injection caused acid and pepsin secretion from the gastric fistula, and both acid and pepsin secretion was significantly increased during beta-adrenergic blockade. Significant gastrin release was observed after insulin stimulation. However, the insulin-induced gastrin release was unaltered by intravenous infusion of propranolol. The Heidenhain pouch did not show any secretion in these experiments. It is concluded that beta-adrenergic blockade augments the hypoglycemia-induced gastric secretion in dogs. Furthermore, it seems that this effect is not dependent on vagally released gastrin.

Non-gastrin, intestinal-phase secretion. Experimental confirmation in the dog.

Four mongrel dogs were prepared with a Heidenhain pouch, a gastric fistula, and a 90-cm-long Thiry-Vella loop. After recovery, dose-response curves were obtained with different doses of pentagastrin, and the maximal acid output was determined. The jejunal loop was perfused for 3 h with either 5% liver extract or with 0.15 M NaCl at a rate of 114 ml/h. To verify that the stomach could release gastrin and that the assay could detect that change, antral perfusion with liver extract was performed. Serum gastrin levels and acid output were measured every 30 min. Perfusion of the jejunal loop with liver extract resulted in a significant increase in acid output from the Heidenhain pouch and the gastric fistula, whereas perfusion with saline solution failed to show any changes. The magnitude of acid response from the Heidenhain pouch and gastric fistula was 11% and 18%, respectively, as compared with maximal pentagastrin stimulation. The serum gastrin levels remained unchanged during both liver extract and saline perfusion of the jejunal loop, in contrast to the marked increase in serum gastrin level after antral perfusion. The results confirm the existence of the intestinal phase of gastric acid stimulation in dogs as an entity and show that the magnitude of this phase is significantly lower than has been suggested by results of earlier studies. Furthermore, the results suggest that the intestinal phase of gastric secretion in dogs is most probably elicited through a humoral agent other than gastrin.

Role of the sympathetic nervous system in peptic ulcer production in rats.

The role of the sympathetic nervous system in gastric acid secretion and in experimental duodenal ulceration (cysteamine induced) was studied in rats. The animals were divided randomly into seven groups: (1) control, (2) sham-operated, (3) surgical sympathectomy, (4) chemical sympathectomy (6-HODA), (5) vagotomy, (6) surgical sympathectomy plus vagotomy, and (7) chemical sympathectomy plus vagotomy. Results on gastric acid secretion were expressed as gastric acid output (GAO = micronEq of acid secretion in 1 hour). The means in the control and sham groups were 447.83 +/- 26.67 GAO and 399 +/- 36.4 GAO, respectively. The means in the sympathectomized rats (surgically = 562 +/- 27.21 GAO and chemically = 648.66 +/- 46.53 GAO) were higher (P less than 0.01) than those of the control and sham groups. In the vagotomized group the mean was 156.6 +/- 17.64 GAO, lower than those of the control and sham groups (P less than 0.001). The incidence of ulceration was 47.5% and 46% in the control and sham groups, respectively. Both the sympathectomized groups (surgically, 73%; chemically, 77%), had a significantly elevated incidence of ulceration as compared with the controls (P less than 0.01). The vagotomized group had a 14% incidence of ulceration. These results clearly indicate that sympathectomy has a definite effect on gastric acid secretion and on the incidence of experimental peptic ulceration in rats.

An electron microscopic study of the distribution of sodium in normal, pentagastrin-stimulated and secretin-inhibited fundic mucosa of the stomach of the rat.

Normal, pentagastrin-stimulated and secretin-inhibited stomachs of rats were fixed either by perfusion or by immersion in an unbuffered osmium tetroxide potassium pyroantimonate mixture at a pH of 7.6, and the mucosa from the fundic area was examined under the electron microscope for sodium localization. Both fixation methods gave comparable results. In the control tissue, sodium pyroantimonate crystals were mainly seen in and around the collagen fibers in the interstitium and to a lesser extent in the basal and lateral plasma membranes of the epithelial cells. No significant differences were noticed in the secretin-inhibited tissue. In contrast, in the pentagastrin-stimulated mucosa, an increase in the amount of precipitate along with a redistribution occurred. The pyroantimonate technique seems promising for studying the mechanism of sodium transport in the gastric mucosa.

Neural control of blood flow in gastric mucosa.

The innervation of the small vessels in the fundic mucosa of the rat and the effects of vagotomy on this innervation were studied ultrastructurally. The capillaries and arterioles, but not the venules, were found to receive direct innervation. Vagotomy causes degeneration of the nerve endings that innervate these vessels, confirming their vagal origin. This finding, and the fact that some morphologic changes in the capillaries were observed after vagotomy, provides morphologic evidence for the neural control of blood flow in the rodent gastric mucosa.

Effects of vagotomy on the catecholamine-containing cells in the gastric mucosa of the rat: an electron microscopic study.

The ECL cells in the fundic mucosa from five different groups of fasted rats were examined by means of electron microscopy; in the control animals, the majority of the secretory granule of the ECL cells contained electron-dense material. Previous studies in our laboratory indicate that this material probably represents a catecholamine. In the second and third groups, in which truncal vagotomy plus pyloroplasty was performed, the secretory granules were depleted of their content. In the fourth group in which vagotomized animals were treated with iproniazid and L-dopa, the mature secretory granules were depleted but formation of new granules was apparent. In the fifth group, in which pyloroplasty alone had been performed, the content of the granules was the same as in the control group. It was concluded that the endocrine function of the ECL cells is under vagal control and that vagotomy causes release of catecholamines from these cells.