Unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer: the utility of positron emission tomography (PET).

The aim of the study was to evaluate the use of positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) in patients with unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer. 50 consecutive patients with elevated CEA levels and a completely normal (n=31) or equivocal (n=19) conventional diagnostic work-up (CDW) were retrospectively selected. All PET images were reviewed with full knowledge of the CDW. The gold standard consisted of histology, or clinical follow-up of more than 1 year. Recurrent disease was established in 56 lesions in 43 patients. On a patient-based analysis, the sensitivity of FDG-PET was 34/43 (79%), and the positive predictive value 34/38 (89%). In 14/50 patients (28%), the FDG-PET findings led to a surgical resection with curative intent. On a lesion-based analysis, FDG-PET detected 42/56 lesions (sensitivity: 75%), the positive predictive value was 79% (42/53). These results demonstrate that FDG-PET can have a clear impact on patient management in patients with an unexplained elevation in CEA levels.

Are carcinomas of the cardia oesophageal or gastric adenocarcinomas?

There is a clear relationship between Barrett's oesophagus and oesophageal adenocarcinoma, and between Helicobacter pylori and gastric cancer, but the histogenesis of cardiac adenocarcinomas is unknown. Some clues as to possible disease associations may be provided by the pattern of gastritis. In our study, we analysed gastritis associated with oesophageal, cardiac and gastric adenocarcinomas according to the Sydney classification. Chronic gastritis was more common in gastric (88%) than in cardiac (56%) and oesophageal adenocarcinomas (38%). H. pylori was significantly more prevalent in gastric (73%) than in cardiac (34%) or oesophageal (21%) adenocarcinomas. Our results show that factors other than H. pylori must be involved in the histogenesis of cardiac adenocarcinomas. As the pattern of gastritis and the clinical features of cardiac adenocarcinomas are more comparable to oesophageal carcinomas than gastric carcinomas, we speculate that most of these tumours share similar aetiological factors with oesophageal carcinomas.

Multifocal epithelioid angiosarcoma of the small intestine.

A 67-year-old man presented with weight loss, intermittent severe abdominal pain and melaena. Initial radiology (including abdominal ultrasonography), gastroscopy and colonoscopy did not demonstrate any lesions that could explain the complaints. Three weeks later, upper gastrointestinal and small-bowel barium studies revealed two areas in the small intestine with an abnormal mucosal pattern. Explorative laparotomy revealed three tumoral lesions. Three partial enterectomies were performed. Gross examination showed centrally depressed dark reddish tumoral lesions extending from the mucosa throughout the full thickness of the bowel wall (diameter varying between 1.6 cm and 2.2 cm). The tumours, composed of large, plump, polygonal cells showing little architectural differentiation, were mainly situated in submucosa and muscularis propria. The growth pattern appeared rather solid. The epithelioid cells showed pronounced nuclear pleomorphism and atypia with central large nucleoli. There were several small blood vessels with occasional anaplastic endothelial cells. Immunohistochemical staining demonstrated an intense expression of CD 31, CD 34, factor VIII related antigen and keratin. This supported the diagnosis of an epithelioid angiosarcoma. The patient died 3 months after diagnosis. Tumours of the small intestine are very rare, and angiosarcomas of the small intestine are even more rare. Epithelioid variants have only been described in two patients and only one of these had a multifocal presentation. The prognosis is very poor. Because of the epithelioid growth pattern and the cytokeratin expression, these tumours may erroneously be diagnosed as a carcinoma.

Contribution of PET in the diagnosis of recurrent colorectal cancer: comparison with conventional imaging.

The clinical value of total body PET with FDG was evaluated in 76 patients presenting with or suspected of recurrent local or distant colorectal cancer. PET results were compared to those of routine imaging (CT pelvis, CT/US liver and CXR). The accuracy of PET for local disease was 95% which was superior to CT-pelvis (accuracy 65%). PET accuracy for liver metastases (98%) compared favourably to CT/US-liver accuracy (93%). Unexpected extra-hepatic mestastases were detected by PET in 14 locations in 10 patients. Also, a primary breast cancer was found in one patient. The main value of PET appeared an improved staging of apparently resectable, local or distant recurrent disease. Thereby, a more adequate indication of major secondary surgery could be attained.

Surgery for gastric remnant carcinoma following Billroth II gastrectomy.

Between January 1983 and December 1995, 31 patients with gastric remnant carcinoma were operated on 6-45 years after a Billroth II resection for peptic ulcer disease. Total gastrectomy with Roux-en-Y reconstruction was performed in all cases. In 16 patients (52%) extended resection with removal of one or more adjacent organs was necessary for oncological reasons. In this elderly population with a high incidence of pre-operative risk factors (55%), most tumours were classified as stage III or IV (45%). Although total gastrectomy should be the surgical option of first choice for gastric remnant carcinoma, it resulted in high levels of post-operative mortality and morbidity (13% and 35%, respectively), especially in patients with stage III and IV tumours who underwent resection of an adjacent organ. Despite extended surgery, if necessary, the recurrence rate after 'curative' surgery is high (8/20 patients) and the cumulative disease-free 5-year survival rate was 48%. Detection of the tumour at an earlier stage not only limits the extent of resection and lowers the complication rate, but also improves survival.

Clinical value of whole-body emission tomography in potentially curable colorectal liver metastases.

AIMS: In selected patients with colorectal liver metastases, hepatic resection offers an opportunity for cure, with a 25-38% 5-year survival rate. The aim of this prospective study was to evaluate whether patient selection could be improved with pre-operative whole-body 18-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scan. METHODS: Ninety-one consecutive patients were considered to be eligible for liver resection after investigation with conventional diagnostic methods (CDM). In all these patients a whole-body PET scan with FDG was performed prior to surgery. Follow-up was complete with a mean of 23 months (2 weeks-92 months). All PET images were reviewed blinded to intraoperative and follow-up data. RESULTS: PET confirmed liver metastases in 90 (99%) patients, while it provided additional information in 10 (11%) patients, i.e., seven intra-abdominal, and three extra-abdominal. PET falsely upstaged six (6.6%) patients in whom malignancy was excluded by additional investigation, at the time of surgery, or during follow-up. PET falsely understaged seven (7.7%) patients with small intra-abdominal lesions. CONCLUSION: In patients with potentially curable colorectal liver metastases according to conventional diagnostic methods, whole-body FDG-PET can be considered as a complementary examination in order to further select patients for potentially curative liver resection, and to optimize therapeutic strategy.

Etoposide, leucovorin and 5-fluorouracil in advanced gastric cancer: a phase II study.

It has been suggested that the combination of etoposide, leucovorin and 5-fluorouracil (ELF) is very active in the treatment of advanced gastric cancer in elderly patients. The aim of this study was to confirm the efficacy and to investigate the toxicity of the ELF-regimen in patients of all ages. Thirty patients with advanced gastric adenocarcinoma were treated with leucovorin (300 mg/m2), etoposide (100 mg/m2) and 5-FU (500 mg/m2) for 3 consecutive days every 4 weeks in a phase II study. Reevaluation of measurable disease was done after 3 cycles. A partial response was shown in 8 (27%) patients. An improvement of the Karnofsky Performance Status was observed in 10 (33%) patients. The mean survival amounted to 8 months (range 2-24). Toxicity was mild. No grade 4 toxicity nor chemotherapy-related mortality were observed. It is concluded from this phase II study that the ELF-regimen is an active palliative treatment for advanced gastric cancer, with mild toxicity.

Intestinal metaplasia in gastric malignancy: a comparison between carcinoma and lymphoma.

OBJECTIVES: Intestinal metaplasia is associated with gastric carcinomas, in particular intestinal-type carcinomas. According to the literature, intestinal metaplasia, especially the sulphomucin-rich incomplete type (type IIb or III) can be considered as a precancerous lesion. Intestinal metaplasia is not uncommon in gastric lymphomas, and the purpose of this study was to determine its prevalence and extent, its different subtypes and the distribution of sulphomucin and to compare these findings with those in gastric carcinomas. DESIGN: The prevalence and grade of intestinal metaplasia were investigated in surgical specimens from 160 patients with gastric carcinoma (102) [intestinal type (69), diffuse type (33)] and gastric lymphoma (58) [marginal zone cell (29), diffuse large cell (29)]. Intestinal metaplasia is analysed by specific mucin stains. METHODS: Intestinal metaplasia was described according to the Updated Sydney system. Using periodic acid-Schiff Alcian Blue pH 2.5 and high iron-diamine/Alcian Blue staining, the intestinal metaplasia was classified (Jass classification) and its sulphomucin content was determined. RESULTS: The prevalence and extent of intestinal metaplasia are significantly higher in intestinal-type carcinomas than all other gastric malignancies. Subtyping of intestinal metaplasia is independent of the different types of gastric neoplasia. High sulphomucin positivity in the metaplastic epithelium is only seen in intestinal-type carcinomas, although in a small number of cases (21.5%). CONCLUSION: Prevalence, extent and sulphomucin content of intestinal metaplasia are significantly higher in intestinal-type gastric carcinoma compared to diffuse-type carcinoma, marginal zone cell and diffuse large cell lymphomas in the stomach.

The use of biochemical parameters for a qualitative and quantitative assessment of ischemic damage to the small-intestinal mucosa.

Lactate dehydrogenase has been measured in the small-intestinal mucosa in order to assess its value as a marker for the effects of ischemia and of reperfusion. The decrease in specific activity of the enzyme illustrates the deleterious effect of reperfusion on the quality of the remaining epithelial cells. However, this parameter fails to detect the loss of epithelial cells, which is the major event during ischemia as well as during reperfusion. In contrast, the expression of enzyme activity per g protein of the underlying intestinal muscle allowed us, in addition, to assess quantitatively the loss of epithelial cells, in good agreement with the histological data.

The medical treatment of colorectal cancer: actual status and new developments.

Colorectal cancer is one of the most frequent malignancies and one of the greatest causes of cancer death in the Western world. The prognosis is determined by the stage at diagnosis. Patients with metastatic colon cancer have a bad prognosis. Chemotherapeutic treatment with 5-Fluorouracil (5-FU) and folinic acid is actually considered as the standard treatment in patients with metastatic disease. Although the survival benefit is relatively small, many patients can benefit from this treatment in terms of tumor regression or symptom improvement. Several new drugs are actually in development and create hope for improved tumor or symptom control and longer survival. Thymidylate synthase inhibitors (raltitrexed), topoisomerase I inhibitors (irinotecan), the oral 5-FU prodrugs (capecitabine, UFT), ethynyluracil, and oxaliplatin are promising new drugs. The challenge will be to determine the best combination of these new drugs and the exact sequence in which these drugs will be used. Adjuvant post-operative chemotherapy in colon cancer is one of the most important advances in oncology that has been introduced into the clinic during the last years. For rectal cancer, an adjuvant treatment should consist of a combined chemo-radiotherapy. The search for better prognostic factors for recurrence should help to focus on a better adjuvant treatment for patients with the highest risk for recurrence.

Different gastritis features are linked to different gastric neoplasms.

OBJECTIVES: Helicobacter pylori infection induces gastritis, which may evolve to carcinoma or lymphoma. Whether duration of infection and inflammation pattern determine the outcome of the neoplastic process is not known. The aim of this study was to investigate the features of the gastritis associated with neoplasia. METHODS: Gastritis found in association with carcinoma (100 cases) and lymphoma (45 cases) were graded using the Sydney system. RESULTS: In particular in the antrum, gastric carcinomas, in particular of the intestinal type, were associated with a chronic (94%, n = 34/36) atrophic (92%, n = 33/36) gastritis and intestinal metaplasia (81%, n = 29/36). In diffuse type carcinomas inflammation was either absent or mild. An active (64%, n = 16/25), chronic gastritis (100%, n = 25/25) with lymphoid hyperplasia (72%, n = 18/25) was found in marginal zone cell lymphoma. CONCLUSIONS: Our study shows that the (pre)atrophic phases of inflammation are associated with gastric carcinomas. In contrast the active phase of inflammation, characterized by severe activity as well as severe chronicity, is found next to marginal zone cell lymphoma.

[Acute intestinal obstruction in an elderly patient]. / Een acute intestinale obstructie bij een oudere patiënt.

The correct diagnosis of an acute abdomen in the aged is difficult, because of its varying presentation. Intestinal obstruction as a cause of acute abdomen is five times more common in the elderly as compared to younger patients. Acute intestinal obstruction in elderly patients may be due to intestinal or gynaecologic malignancies, or more frequently to incancerated hernias, peritoneal adhesions or faecal impaction. This case report describes a 90-year old female patient with intestinal obstruction, due to a bilateral torsion of benign ovarian cysts. Urgent surgery was life-saving. This case demonstrates that early decision for adequate therapy can reduce morbidity and mortality, also in very old patients.

Radical versus local surgical treatment for rectum carcinoma. A variety of options?

Local excision has to be classified as either indeterminate or non curative from a surgical oncological point of view. It seems to be an acceptable procedure for well differentiated, exophytic/polypoid pT1 lesions of less than 3 cm in diameter, providing the resection margins are tumour-free. For all other lesions radical surgery is to be preferred, unless the patient is unfit for major surgery or refuses an eventual permanent colostomy. Complete local excision followed by radiation therapy may become a valuable alternative for well differentiated, small pT2 lesions, but results are too preliminary. If radical surgery is indicated, the distal clearance margin (to be measured in the fresh, unstretched specimen) may be reduced to 2 cm if taking more distal tissue would jeopardise the anal sphincter. The mesorectum should be completely cleared in patients with low- or mid-rectal cancer. A benefit of excision of the internal iliac nodes in rectal cancer below the peritoneal reflection has not been demonstrated. Low anterior resection is the operation of choice for carcinoma with its lower border above 8 cm from the anal verge. Complete, restorative rectum excision with colo-anal anastomosis (CAA) is the option for tumours with their lower border between 6 and 8 cm from the anal verge if an acceptable margin of distal clearance is obtained. Rectal cancer with its distal border below 6 cm usually requires abdominoperineal rectum excision, although restorative proctectomy with CAA may be a valuable alternative in selected patients with small, well or moderately differentiated tumours.

Planned relaparotomies for advanced, established peritonitis from colonic origin.

Patients presenting diffuse, advanced, established peritonitis due to free perforation of the colon, in whom an adequate abdominal debridement cannot be obtained in one operative session were selected. We report results of the planned relaparotomy approach in 44 patients as compared with an historical series of 9 analogous patients treated by on demand exploratory relaparotomies. Planned relaparotomies were performed every 2 days until the abdominal cavity became macroscopically clean. This approach significantly reduced both the incidence of multiple organ failure and the mortality rate (31%) as compared with the regimen of on demand relaparotomy. The mortality rate in the planned relaparotomy group is related to the age of the patient and to the nature of peritonitis. Faecal peritonitis carries a higher mortality rate than purulent peritonitis. The mortality rates of severe postoperative peritonitis and advanced primary peritonitis were not significantly different. Surgery for severe, diffuse peritonitis has to be prompt, moderately aggressive and repeated if necessary. Therefore, planned relaparotomies have a place in the treatment of selected patients presenting diffuse, advanced, established peritonitis.

Pouch-sacral fistula three years after restorative proctocolectomy for ulcerative colitis.

Fistula formation after restorative proctocolectomy poses a challenge to the surgeon and sometimes can lead to the excision of the pouch. A 21-year-old female patient developed an ileal J-pouch-sacral fistula with abscess and osteomyelitis of the sacrum, more than three years after the pouch construction for ulcerative colitis. Two months prior to this event, the patient had a single and transient episode of pouchitis. The role of pouchitis in the aetiopathogenesis of the fistula is unclear. To our knowledge, the late development of such a fistula has not been reported previously.

Influences of ischemia and reperfusion on the feline small-intestinal mucosa.

The alterations of several small-intestinal mucosal enzymes have been examined in cats that underwent different periods (1-4 hr) of occlusion of the superior mesenteric artery, followed by 4 hr of reperfusion. The damage progressed during ischemia and reperfusion from the villus tips to the crypts: first, there was a rapid decrease in the activity of maltase, a brush-border enzyme; a slower decline occurred in two cytoplasmic enzymes, aldolase A (with preferential location in feline villus cells) and lactate dehydrogenase (with an ubiquitous distribution); a lag preceded the decrease in aldolase B (a cytoplasmic enzyme shown to occur mainly in feline crypt cells). For all these enzymes, the initial period of reperfusion was associated with a greater decrease in enzyme activity than persisting ischemia. By determination of the unsedimentable proportion of glutamate dehydrogenase (a mitochondrial matrix enzyme) and of acid phosphatase (a lysosomal enzyme) it was demonstrated that ischemia caused important mitochondrial damage before the cells were lost, whereas no lysosomal damage was observed in any condition. These sensitive parameters of cell damage can serve as a criterion for an adequate evaluation of potential cytoprotective agents.

Advancement flap plasty for the closure of anal and recto-vaginal fistulas in Crohn's disease.

The management of anal fistulas in patients with IBD continues to be extremely challenging and, indeed, somewhat frustrating. Despite a global closure rate of about 75%, all patients should be informed about the risk of infection, early failure, eventual temporary disfunctioning stoma and the possibility of late recurrence (about 15%). Closure of a RVF in Crohn's disease should not be considered an easy undertaking, especially in patients with several Crohn localisations. The technique can be adapted to the local situation. Construction of a temporary stoma is not mandatory. However, stoma construction seems to be beneficial when extensive perianal or recto-vaginal dissection including eventual tissue interposition is required. Advancement flaps are an attractive surgical alternative for the management of all anal transsphincteric fistulas, also in Crohn's disease, because sphincter architecture and function are well preserved. Improved medical treatment and the changed approach from conservative to reparative surgery may well have resulted in a decreased need or at least in a delay of the need for a proctectomy. Although the surgical principles of advancement flap techniques are sound, these techniques have not been used for many decades. Skills needed, problematic approach, suboptimal quality of local tissues have contributed to its selective use and to the absence of prospective randomised studies.

Restorative proctocolectomy in elective and emergency cases of ulcerative colitis.

A consecutive series of restorative proctocolectomy for ulcerative colitis was reviewed to determine whether an emergency restorative proctocolectomy procedure leads to a higher morbidity, more especially anastomotic leakage. Severity of illness and nature of surgery were divided in two categories: (1) no acute disease and elective surgery (18 patients), (2) acute disease requiring emergency surgery either immediately or within one week of admission (12 patients). Morbidity after elective surgery was 27% and after emergency surgery 66% (P < 0.06). Pouch-anal leakage occurred in 11% and 41% respectively (P = 0.08). Five risk factors significantly influenced the leak rate including preoperative white blood cell count > 10,000/microliter (P < 0.02), urgent nature of surgery (P < 0.02), the combination of leucocytosis and urgent nature of surgery (P = 0.02), the combination of leucocytosis and preoperative corticosteroid dose equivalent to > or = 200 mg hydrocortisone/24 h (P = 0.006), postoperative pelvic haematoma (P < 0.05). In conclusion, restorative proctocolectomy is contraindicated in emergency circumstances, especially in patients with signs of sepsis on a high corticosteroid dose. To reduce operative risk and number of procedures required, patients with relapsing ulcerative colitis should be referred for restorative proctocolectomy while being in remission.