A metastatic colon cancer model using nonoperative transanal rectal injection

Background  

This study aimed to develop a noninvasive orthotopic model for metastasis of colon and rectal cancer using a transanal approach. Currently, the most accurate orthotopic representation of metastatic human colon cancer is via a cecal injection. The transanal model allows for further examination of systemic immune responses, tumor take, and onset of metastasis without prior surgical intervention.     

Incidence of isolated metastatic organ involvement in rectal cancer in an autopsy sample

From the rectum carcinoma cases diagnosed and reported to the National Cancer Registry in 1980, 886 were submitted to obduction. Metastases were detected in 46.8% of the autopsy material. Affected were the liver in 38.7%, the lung in 16.1%, and the skeleton in 3.5% of the obducted cases. The pattern of metastases depended on the histological picture of the carcinoma: with adenocarcinomas, haematogenic metastases, and with mucigenic adenocarcinomas, lymphogenic metastases were predominant; the signet-ring-cell carcinomas develop their pronounced metastatic potency in either way. The isolated liver affection could be established in 9% of all liver metastatic patients who underwent radical operation, and in 22% following exclusion of a presacral recurrence, respectively. A histologically oriented scheme is proposed to complete the spreading diagnostics and to establish a therapeutic concept for liver metastases, and an additional, targeted, systematic intraperitoneal and endolymphatic application of cytostatic substances in the treatment of liver metastases to reduce the extrahepatic metastatic rate is discussed.     

Loss of c-met protooncogene in primary and metastatic sites of breast cancer

Background: It has been proposed that clones of tumor cells acquire higher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncogene in systemic spread by comparing the loss of the c-met protooncogene between primary and metastatic breast carcinomas. Methods: Only patients who had not received chemotherapy or radiotherapy in the preceding 6 months were included in this study. Histologically proven malignant tissue was obtained from the primary tumor, involved nodes, and distant metastatic and recurrent tumors of patients with breast carcinomas. Allelic loss of the c-met protooncogene in tumor tissue was determined by Southern blotting using a polymerase chain reaction-generated 347-bp human met-H probe. Restriction digestion was performed usingTaq I andMsp I, with the patient's lymphocyte DNA as controls. Results: Of 52 patients, lymphocyte DNA from 36 patients was heterozygous for the c-met protooncogene (69% informative). Forty-six tumors from these 36 patients were analyzed. Four of 30 primary tumors (13%) showed allelic loss of c-met. Of the nine nodal metastases examined, three (33%) showed allelic loss of the c-met protooncogene. Of seven distant metastatic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall). Conclusions: Allelic loss of the c-met protooncogene was detected in both primary (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/recurrent disease, the difference when compared with the primary tumor was not statistically significant. These findings indicate a limited role of the c-met protooncogene in breast cancer metastases.     

超低位直肠癌新辅助治疗后淋巴结分布及转移规律

目的探讨新辅助治疗对超低位直肠癌淋巴结转移及其微转移规律及分布的影响,为手术方式的选择提供依据。方法运用大组织切片苏木精．伊红染色和组织芯片CK20染色方法,研究超低位直肠癌新辅助治疗组（21例）与直接手术组（23例）行Miles手术后的大体标本。结果新辅助治疗组21例患者直肠系膜共检获淋巴结138枚．其中转移淋巴结39枚,微转移12枚：7例为淋巴结癌转移。2例为淋巴结微转移,6例为病理完全缓解。直接手术组23例患者的直肠系膜共检获淋巴结415枚,其中转移淋巴结169枚,微转移59枚：12例为淋巴结癌转移,4例为淋巴结微转移。两组直肠系膜外带与前区的转移淋巴结分别占21．5％（11／51）与29．0％（49／169）、17．6％（9／51）与17．2％（29／169）。坐骨直肠窝转移淋巴结分别占该区总淋巴结的25．0％（3／12）与22．2％（8／36）,该区淋巴结转移或微转移者分别占总病例数的4．8％（1／21）与13．0％（3／23）。结论新辅助治疗影响超低位直肠癌区域淋巴结的转移与分布．新辅助治疗组肛门括约肌累及较直接手术组显著降低。坐骨直肠窝内极少发生淋巴结转移,Miles手术作为超低位直肠癌新辅助治疗后标准术式的价值应重新评估。     

Endoscopic transanal resection provides palliation equivalent to transabdominal resection in patients with metastatic rectal cancer

Patients with metastatic rectal cancer precluding curative low anterior resection (LAR) or abdominoperineal resection (APR) can require palliation for impending obstruction. LAR or APR is frequently not optimal because of the associated operative morbidity. Lesser procedures such as diverting colostomy require patients to live with a permanent stoma. Endoscopic transanal resection (ETAR) has been used for excision of rectal lesions. To determine whether ETAR provides palliation equivalent to LAR or APR, we reviewed the outcomes of 49 patients with rectal adenocarcinoma and unresectable liver metastases who required palliative intervention between January 1989 and July 1996. Of these 49 patients, 24 underwent ETAR; the intraluminal tumor was resected using the urologic resectoscope to achieve a hemostatic, patent lumen. The outcomes of these patients were compared to those of the other 25 patients who had palliative LAR, APR, or a Hartmann procedure during the same period. The median distance of the tumors from the anal verge was similar (5 cm; range 1 to 15 cm). ETAR patients had a higher percentage of poorly differentiated tumors (35% vs. 6%, P = 0.034) and higher preoperative alkaline phosphatase values (478 ±75 mg/dl vs. 231 ±24 mg/dl; P<0.015), suggesting more aggressive disease and greater hepatic tumor burden, respectively. Despite these differences, overall survival and time spent outside the hospital were similar in the two groups. The median number of debulking procedures required in the 24 ETAR patients was two (range 1 to 17). Resections in the 25 LAR/APR patients included LAR in 20, APR in two, and Hartmann procedures in three. There was a trend toward more stomas in the LAR/APR group (28% vs. 17%). More important, morbidity was significantly higher in the LAR/APR patients (24% vs. 4%; P = 0.049). In conclusion, ETAR is a safe alternative for the palliation of incurable rectal tumors. Compared to transabdominal resection, ETAR provides equivalent palliation as measured by survival and proportion of the patient’s life spent outside the hospital, with a lower stoma rate and significantly less morbidity. Therefore, in select patients with metastatic rectal cancer, ETAR is an important palliative option. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 2l–24, 2000.     

Case report of diffusely metastatic rectal GIST

This is a case report of an aggressive, diffusely disseminated Stage IV rectal gastrointestinal stromal tumor (GIST) in a 57-year-old male that presented for symptoms of malaise, constipation, and twenty pound weight loss in 2 months. Upon rectal examination, a hard 4 centimeter submucosal mass was found at the 9–12 o’clock position. Liver and lung metastases were visualized on computerized tomography (CT) of the chest, abdomen, and pelvis on metastatic work-up. He was deemed a poor surgical candidate due to diffuse metastatic disease and referred for palliative chemotherapy. The patient had suffered a perforation of his rectal wall two weeks after his initial presentation and passed away shortly thereafter. He never received palliative chemotherapy. We present a case report as a unique case of an extremely aggressive and quickly fatal GIST tumor.     

Ureteroscopic diagnosis of intraluminal metastatic rectal carcinoma

Ureteral obstruction resulting from metastatic adenocarcinoma is almost always extrinsic in nature. In contast, true intraluminal metastases are extremely rare. With this report, we document the videoendoscopic appearance of true intraluminal ureteral metastases from metastatic rectal cancer confirmed with histopathologic examination. The value of transureteroscopic biopsy for accurate diagnosis is also demonstrated.     

Atypical endoscopic features can be associated with metastasis in rectal carcinoid tumors

Background  Endoscopically, rectal carcinoids have a variety of sizes and features which may assist in determining treatment plans. The present study was performed to assess the relationship between endoscopic features and metastasis in rectal carcinoids. Methods  A total of 115 rectal carcinoids of 112 patients with rectal carcinoids were enrolled, and the medical records were retrospectively reviewed. All tumors were classified according to size (longest diameter), and then according to endoscopic features such as shape, color, and surface changes including depressions, erosion, and ulceration. The relationship between endoscopic features and metastasis was evaluated. Results  11 cases (9.6%) of the 115 rectal carcinoids presented with metastatic disease. Tumor size was associated with metastasis (p < 0.001). Endoscopic features associated with metastasis were tumor shape, surface change, and color (p < 0.001). Atypical endoscopic features occurred more frequently as the size of the tumor increased (p < 0.001). For tumors 10–19 mm in diameter, atypical surface change was associated with metastasis (p = 0.007). Conclusions  Endoscopic features were found to be associated with metastasis in rectal carcinoids. In particular, atypical surface change may be useful in determining treatment plans for tumors 10–19 mm in diameter.     

Cryosurgery in inoperable rectal cancer

26 patients suffering from nonresectable adeno-carcinoma of the rectum have been treated since Sept. 1980. The mean age was 72 years. The temperature of the probe tip was -160 degrees C. A closed system with liquid nitrogen was used. In 12 patients there was an indication of systemic inoperability, 13 had an irremovable tumour or metastases. 1 patient refused curative operation. Cryosurgery was aimed at reducing the mass of rectal tumours and preventing colostomy. Colostomy could also be avoided in 12 of 14 patients suffering from stenosing tumours. The advantages of cryotherapy are outpatient treatment, no anaesthesia and minimal complications. Generally, this method will yield good results in palliative treatment of inoperable rectal carcinomata.     

Therapeutic policy in rectal cancer

The results of clinical examination and treatment of 751 patients with rectal cancer are presented. A total of 684 (91.0%) patients underwent radical surgery. In 439 (64.2%) from them sphincter saving operations were carried out. The rate of sphincter saving procedures for the last 5 years has increased up to 73.8%, most often of them transbdominal resection was used--284 (64.7%) patients. Sygmoidorectal anastomosis in 158 (55.6%) patients was carried out by the hand sutures, and in 126 (44.4%)--suturing apparatuses were used. The operation was finished by the suture of the pelvic peritoneum by two layers of sutures and the drainage of the area of the anastomosis from the perineum site by two tubes for prevention of the development of peritonitis even in case of insufficiency of the anastomosis was made. All the operated patients underwent preoperative radiotherapy with a total dose 20-25 Gy. The basic stage of the operation was on demand followed by chemohyperthermic perfusion of the abdominal cavity. It was carried out in 30 patients, including 12 patients with rectal cancer. In cancer of the rectum of the II B and III stages the usage of chemotherapy is obligatory. New operations for metastases of cancer of the colon into the liver were made in 4 patients (left and extended right hemihepatectomy). Complications developed in 33.5% of patients, lethality made up 3.8%, including 1.8% for the last 5 years.     

Recurrent liver tumor with intrabiliary ductal growth after hepatectomy for metastatic rectal cancer: Case report

A case of recurrent tumor with intrabiliary ductal growth after hepatic resection for liver metastasis from rectal cancer is presented. The patient, a 55-year-old female, underwent subsegmentectomy of the anteroinferior and posteroinferior areas of the liver for metastatic liver cancer on August 29, 1988. Computed tomography in February 1990 showed dilatation of the intrahepatic bile duct in the right anterosuperior subsegment (B8), in which a filling defect was detected by cholangiography through a percutaneous transhepatic biliary drainage (PTBD) catheter. Percutaneous transhepatic cholangioscopy (PTCS) revealed a protruding lesion without tumor vessels. Cholangioscopic biopsy revealed dysplasia, but not adenocarcinoma. However, recurrent tumor originating in the resected margin of the remnant liver was suspected, and resection of the right lobe of the liver and partial resection of the duodenum were therefore performed. The resected specimen showed a tumor, 4 cm in diameter, in the previous resected margin, forming a protruding lesion with a rough surface (measuring 10×20 mm) in the B8 bile duct. This case suggested the possibility of cancer recurrence in the resected margin of the liver after hepatectomy for metastatic colorectal cancer, with intrabiliary ductal tumor growth showing segmental biliary dilatation.     

Sphincter-sparing operations in rectal cancer

Data on 564 patients who underwent operation for cancer of the rectum are analysed. Amputation of the rectum was resorted to most frequently because of the low localization of the neoplastic process in the majority of patients. Mortality was higher in amputation than in anterior resection of the rectum. Criteria for sphincter-preserving operations are determined. Preference is given to anterior resection of the rectum as a more physiological operation which was also performed on elderly patients.     

Endorectal ultrasound in rectal cancer

Accurate staging of rectal carcinoma is crucial for planning surgery and the indication for adjuvant therapy. Although computed tomography and magnetic resonance imaging are very sensitive in the detection metastastic disease, local staging of rectal cancer with these techniques has been disappointing. Endorectal ultrasound (EUS) remains the most accurate method for staging of rectal cancer. High accuracy rates in the assessment of the depth of infiltration (T stage) (80–90%) and in the determination of the lymph node status (70–80%) have been confirmed in several studies. Continued research and development has made the instrumentation for EUS more accurate and user‐friendly. New techniques that have contributed significantly to the evolution of EUS include three‐dimensional EUS, high‐frequency miniprobes and transrectal ultrasound‐guided biopsy techniques. Further improvement can be expected by contrast enhancement with microbubbles and colour Doppler imaging.     

Preoperative radiotherapy in rectal cancer

A review is made of the clinical experience of preoperative radiotherapy in patients with operable cancer of the rectum or rectosigmoid. The randomized clinical trials that have been reported are evaluated. It is concluded that preoperative irradiation using a dose of no less than 34.5 gray in 15 daily fractions [Nominal Standard Dose (NSD) 1,290] can reduce locoregional recurrences and improve disease-free survival. Doses of this order are not associated with any significant increase of morbidity. The administration of lower doses has not been confirmed to be of any benefit. It is suggested that patients with fixed or partially fixed cancers of the rectum or rectosigmoid should be selected for preoperative adjuvant radiotherapy. This group has a low probability of undergoing curative resection without adjuvant treatment. Local recurrence is high and survival poor in this group of patients. Patients with mobile cancer of the rectum should probably proceed to definitive resection and be considered for postoperative radiotherapy (perhaps combined with chemotherapy) if found to have Dukes' stage B or C cancer. This policy also minimizes the probability of irradiating patients with Dukes' A cancer who are unlikely to benefit from such adjuvant treatment.

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Resumen Se hace una revisión de la experiencia con radioterapia preoperatoria en pacientes con cáncer operable del recto o del recto-sígmoide y se valoran los ensayos clínicos aleatorizados que han sido informados por diferentes instituciones. Se llega a la conclusión de que la irradiación preoperatoria utilizando una dosis de no menos de 34.5 gray en 15 fracciones diarias (NSD 1,290) puede reducir la tasa de recurrencia locorregional y mejorar la supervivencia libre de enfermedad. Dosis de este orden no están asociadas con un incremento significativo de la morbilidad. La administración de dosis menores no ha probado ser de beneficio.Se sugiere que los pacientes con cánceres fijos o parcialmente fijos del recto o del recto-sigmoide deben ser seleccionados para radioterapia preoperatoria adyuvante. Este grupo tiene una baja probabilidad de resección curativa sin terapia adyuvante; la tasa de recurrencia local es elevada y la supervivencia es pobre.En los pacientes con cánceres móviles del recto probablemente se puede proceder con la resección definitiva y pueden ser considerados para radioterapia postoperatoria (tal vez combinada con quimioterapia) si son cánceres en estados Dukes B o C. Esta política también minimiza la probabilidad de irradiar pacientes con cáncer Dukes A, quienes generalmente no se benefician con este tipo de terapia adyuvante.

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Résumé Une revue de l'expérience clinique de la radiothérapie préopératoire pour cancer du rectum et du recto-sigmoide a été effectuée par l'auteur. Les essais cliniques randomisés qui concernent la méthode, déjà publiés, ont été étudiés. Il est possible à partir de cette étude d'affirmer que l'irradiation préopératoire avec une dose supérieure à 34.5 gray fractionnée en 15 jours (NSD 1,290) peut entrainer une réduction des récidives locales et améliorer le taux de guérison. Une irradiation de cet ordre de grandeur ne s'accompagne d'aucune augmentation significative de la morbidité. Le recours à des doses inférieures n'a été d'aucun bénéfice.L'auteur conseille de traiter les malades qui présentent un cancer fixé du rectum ou du recto-sigmoide par la radiothérapie pré-opératoire car les chances de guérison dans ces cas sont faibles, en l'absence de ce traitement complémentaire. Le taux des récidives est élevé et celui de la survie est faible.Les malades qui présentent une tumeur mobile du rectum devraient être soumis à la radiothérapie post-opératoire et éventuellement à la chimiothérapie si le cancer répond aux types B et C de la classification de Dukes. En revanche, le cancer de type A ne relève pas de ce traitement complémentaire.