Mucinous colorectal adenocarcinoma with signet-ring cells: immunohistochemical and ultrastructural study.

A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as revealed after histological evaluation, was examined ultrastructurally. The authors also analyzed the immunohistochemical data of the tissue for serotonin, vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon, using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling method for light and electron microscope, respectively. Electron microscopically mucinous adenocarcinoma was characterized by the formation of small lumen. Adenocarcinoma cells were full of mucous granules of varying electron density, providing a good environment for the tumor cells to grow. They also exhibited a significant loss of microvilli and intracytoplasmic junctions, which could allow the cells to disseminate. Signet-ring cells were located in the basal site of the ducts or in the lamina propria and appeared neoplastic, with mucin accumulation intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic organelles were decreased and at the periphery of the cell. The PAP method demonstrated that these cells were strongly positive for bombesin and also positive for vasointestinal polypeptide (VIP). The immunogold method detected bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic membranes, whereas VIP was localized mainly in the plasma membrane. The location of signet-ring cells combined with the immunoreactivity for bombesin and VIP indicated that signet-ring cells were of neuroendocrine origin and probably dedifferentiated enterochromaffin-like endocrine cells. These findings have implications for understanding the biological behavior of these composite malignant tumors and could help in the knowledge of the origin of signet-ring cells.

Self-expanding plastic stents for inoperable malignant strictures of the cervical esophagus.

Dysphagia and respiratory complications are the major problems in patients suffering from malignant strictures of the cervical esophagus. In inoperable cases, interventional palliation is the cornerstone of treatment. The aim of this study was to evaluate the use of self-expanding plastic stents (SEPS) in this group of patients. In a retrospective study, 23 patients suffering from various malignant obstructive diseases of the cervical esophagus, including squamous cell carcinoma (n = 10), laryngeal cancer (n = 7), lung cancer with esophageal invasion (n = 5), and metastatic breast cancer (n = 1), underwent SEPS placement, under endoscopic and fluoroscopic guidance. Tracheoesophageal fistula was documented in five patients. Technical success rate, improvement of dysphagia grade, and stent-related complications were evaluated after stent placement. Stent insertion was successfully achieved in all cases, namely in 20 patients at the first stent placement attempt and in three patients after a second attempt. Dysphagia grade was notably improved after 24 h. In two cases, major complications occurred. These were successfully treated without the need of stent extraction. Barium swallowing studies demonstrated complete sealing of all fistulas. Foreign-body sensation that gradually disappeared within the first week after stent placement was observed in eight patients. Recurrence of dysphagia occurred in three patients, due to hyperplastic tissue proliferation (n = 2) and tumor overgrowth (n = 1). Late migration of the stent was detected in one case after 67 days. SEPS placement is an effective and safe palliative treatment for malignant strictures of the cervical esophagus. Main advantages include easy retrievability and reduced rates of reinterventions.

Gemcitabine as palliative treatment in patients with unresectable pancreatic cancer previously treated with placement of a covered metal stent. A randomized controlled trial.

PURPOSE: To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL). PATIENTS AND METHODS: Forty-nine patients with unresectable PC and obstructive jaundice, previously treated with the placement of a covered metal biliary endoprosthesis, were randomized to receive gemcitabine (group A: 9 males, 7 females) or to be followed without any anticancer intervention (group B: 18 males, 15 females). Gemcitabine was administered weekly as intravenous (i.v.) 30 min infusion of 1000 mg/m2 for 3 consecutive weeks followed by 1-week rest (28-day cycle). QoL was evaluated with the QLQ-C30 questionnaire. RESULTS: 229 gemcitabine doses were administered (median doses per patient 14.3, range 7-22). No statistically significant differences were observed regarding survival (group A: median 21 weeks, range 13-33; group B: median 22 weeks, range 13-29; p=0.809). According to the average QLQ-C30 score, group B patients showed statistically significant higher values (p=0.0001). Leukopenia, neutropenia, thrombocytopenia and anemia were the most common side effects in group A (81.25, 68.75, 62.50 and 31.25%, respectively). CONCLUSION: Gemcitabine didn't show to improve survival and QoL in patients with advanced PC previously treated with a covered metallic biliary endoprosthesis due to obstructive jaundice.

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial.

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5 mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30 mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49+/-6 wk) as compared to the control group (28+/-1 wk) and to the SSTR negative group (28+/-2 wk), LR=20.39, df=2, P<0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group, respectively. CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

Short-term preoperative radiotherapy in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

PURPOSE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (RT) (5x5 Gy) not only reduces the risk for local recurrence, but also improves the overall survival rate. However, an increase in postoperative mortality and morbidity has also been observed. We, therefore, evaluated the early postoperative complications in patients treated with neoadjuvant RT for locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on computed tomography (CT) scan and, in several cases, with endorectal ultrasonography. There were 55 men and 30 women, with a median age of 68 years. Patients were retrospectively divided into two groups: group A, which included 40 patients receiving preoperative RT (25 Gy in 5 fractions), followed by surgery within one week, and group B, which included 45 patients with rectal cancer undergoing surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS: No postoperative deaths were recorded in either group. In group A, complete pathologic response was observed in 6 (15%) patients and microscopic residual cancer was found in 8 (20%). Low anterior resection (LAR) with total mesorectal excision (TME) was performed in all group A patients, whereas 8 patients in group B underwent abdominoperineal resection (APR) (p < 0.05). Diverting stoma was performed in 7 patients of group A; this was closed 3-6 months later in all cases. Postoperative morbidity was not statistically significant between the two groups (40% versus 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection and delayed ileus was similar. The percentage of major anastomotic leak was also similar in both groups (5 versus 6.6%). CONCLUSION: Short-term preoperative RT in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

Palliative treatment of advanced esophageal cancer with metal-covered expandable stents. A cost-effectiveness and quality of life study.

PURPOSE: The aim of this retrospective study was to evaluate the efficacy and safety of endoscopic therapy with self-expanding metallic endoprostheses in the management of inoperable primary malignant esophageal obstruction or stenosis and the cost-effectiveness of the method. PATIENTS AND METHODS: Between 5/1997-12/2002, obstruction of the esophagus was diagnosed in 78 patients (52 males, 26 females, age range 53-102, mean 72.3 years). The etiology was squamous cell carcinoma (n=42) and adenocarcinoma of the oesophagus (n=36). In total, 89 ultraflex metal stents were introduced endoscopically. In 46 patients dilation with Savary dilators prior to stent placement was required. A cost-effective analysis was performed, comparing oesophageal stenting with laser therapy. RESULTS: Stents were placed successfully in all patients. After 48 h, all patients were able to tolerate solid or semi-solid food. During the follow-up period 8 patients developed dysphagia due to food impaction (treated successfully endoscopically). Eleven patients developed recurrent dysphagia 4-16 weeks after stenting due to tumor overgrowth and were treated with placement of a second stent. The median survival time was 18 weeks. There was no survival difference between squamous cell and adenocarcinoma of the esophagus. A similar cost was calculated for both procedures. A significant improvement in quality of life was noted in patients undergoing stenting (96% and 75% vs. 71% and 57% for the first two months). CONCLUSION: Placement of self-expanding metal stents is a safe and cost-effective treatment modality that improves the quality of life, compared with laser therapy, for patients with inoperable malignant esophageal obstruction.

Primary melanoma of the oesophagus treated endoscopically. A case report.

Primary melanoma is a rare neoplasm of the oesophagus, with dismal outcome in most cases. We report a case of primary melanoma of the oesophagus treated endoscopically, as coexisting illness prohibited surgical resection of the tumour. A review of the literature is made.

Stenting or stoma creation for patients with inoperable malignant colonic obstructions? Results of a study and cost-effectiveness analysis.

BACKGROUND: The aim of the present study was to compare the efficacy, safety, and cost of endoscopic palliative treatment with selfexpanding metallic stents with that of stoma creation in the management of inoperable malignant colonic obstructions. METHODS: A total of 30 patients with inoperable malignant partial obstruction (due to metastases, hemodynamic instability, or pulmonary instability) in the left colon arising from colorectal or ovarian cancer were included in the study. Fifteen were randomized to undergo palliative metallic colonic stent placement and 15 to undergo stoma creation. The efficacy and safety of the two methods was compared. A cost-effectiveness analysis was also performed, including the cost of postinterventional care. RESULTS: Stents were placed successfully in 14 of 15 patients. In one patient with obstruction of a tortuous rectosigmoid flexure colon, stenting was not possible; this patient was excluded from the study. During the follow-up period, a moderate, nonocclusive ingrowth of tumor into the stent lumen was observed in six patients; they were all treated with internal laser ablation. The cost-effectiveness analysis showed that although the stoma creation procedure was less expensive, the total difference in average costs for the two methods was 6.9% (132 Euros). CONCLUSIONS: Self-expanding metallic stent placement is a palliative alternative to colostomy for patients with inoperable malignant colonic strictures. This treatment option provides a better quality of life for the patient, without the psychological repercussions of a colostomy, and it appears to be cost-effective.

Treatment of malignant colonic obstructions with metal stents and laser.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and safety of combined endoscopic therapy with self-expanding metallic endoprostheses and laser application in the management of malignant colonic obstruction. METHODOLOGY: Between March 1998 and September 2000, obstruction of the distal colon was diagnosed in a total of 11 patients (6 M, 5 F, age range: 67-87 years, mean: 73). The site of obstruction was located in the rectosigmoid colon (n = 6), in the sigmoid colon (n = 4) and in the descending colon (n = 1). The etiology of stenosis was colorectal adenocarcinoma (n = 8), ovarian cancer (n = 2) and infiltrating bladder carcinoma (n = 1). In all patients the tumor was considered non-resectable. Six patients had confirmed metastases, one refused colostomy and 4 were unable to undergo surgery. After radiological visualization of the proximal extent of the stricture, the stenosis was dilated with Savary-like (10 patients) and pneumatic balloon dilators (1 patient-descending colon). RESULTS: Stents were placed successfully in 10 patients. Prostheses migration distal to lesion, into the sigmoid colon, was observed in one patient (bladder cancer). A mild autoresolved bleeding was observed in 8 patients. Five patients remained free of clinical colonic obstruction until their death, which occurred 6-16 weeks (mean: 10) after stent placement. A moderate non-occlusive ingrowth of tumor into the stent lumen was documented in the other 5 cases. These patients were treated with introspective application of Diomed laser in a total of 16 sessions (4120-12,476 Joules each session, mean: 6258, power 10-14 W, interval between 2 sessions 6 weeks) and died of progressive disease without clinical signs and endoscopic findings of reobstruction 22-56 weeks (mean: 32) after stent placement. CONCLUSIONS: Metallic stent placement is an adequate palliative and cost-effective option, effective and save, in advanced colonic obstruction due to non-resectable tumors. It circumvents the need for colostomy and allows the patient a better quality of life. Delayed stent occlusion with tumor ingrowth requires a regular follow-up and can be treated with introspective laser ablation.

Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer.

BACKGROUND AND AIMS: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5x5 Gy) not only reduces the risk of local recurrence but also improves overall survival rate. An increase in postoperative mortality and morbidity has also been observed, however. We therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma. PATIENTS/METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on CT scan and, in several cases, on endorectal ultrasonography. They were 55 men and 30 women, with a median age of 68 years. They were retrospectively divided into two groups: Group A, which included 40 patients undergoing preoperative radiotherapy (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of the disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS/FINDINGS: No postoperative deaths were recorded in either group. Low anterior resection with total mesorectal excision was performed in all group A patients, whereas eight patients in group B underwent abdominoperineal resection (P<0.05). Diverting stoma was performed in seven patients of group A and it was closed 3-6 months later on every occasion. Postoperative morbidity was not statistically significant between the two groups (40 vs 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. The percentage of major anastomotic leak was also equivalent (5 vs 6.6%). INTERPRETATION/CONCLUSION: Short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.

Immune thrombocytopenic purpura in a patient treated with interferon alfacon-1.

Immune thrombocytopenic purpura is an acquired disorder characterized by severe thrombocytopenia and caused by one or more antiplatelet autoantibodies. We present a case of a 20-year-old woman referred to our Unit for chronic hepatitis C virus (HCV) infection. At week 28 of treatment with interferon (alfacon-1), undetectable HCV RNA and transaminase levels within normal limits, the patient presented with immune thrombocytopenic purpura, which was successfully treated with immunoglobulin and methylprednisolone. Despite the high doses and long life of corticosteroid treatment HCV RNA remained undetectable.