Local recurrence in sigmoid cancer is a hidden problem,could CT prognostic factors be of value in their prevention? A multi-centre study of 414 patients

IntroductionThe incidence and patterns of local recurrence of colon cancer are not well reported. The aim of this study was to investigate the contemporary rates and patterns of local recurrence after sigmoid cancer resection, comparing pre and post-operative biomarkers in predicting local disease recurrence.Materials and methodsA multi-centre, retrospective analysis of 414 patients undergoing resectional surgery for sigmoid colon cancer was conducted. Multivariable Cox Proportional Hazard models were created to identify variables associated with local disease recurrence. Patterns of recurrence and prognostic significance of pre and post-operative variables were identified.ResultsIn 414 patients, the local recurrence rate was 12.6%. The R1/R2 rate was 2.4%. Local recurrence occurred most commonly within the peri-anastomotic region (50%), followed by the peritoneum (33%). On multivariate analysis, local recurrence was predicted by pathological T stage (HR 1.15) and R1 resection (HR 2.95), but also computerised tomography (CT) identified tumour deposits (HR 2.40) and local peritoneal infiltration (2.70).ConclusionsContemporary local recurrence rates for sigmoid cancer are high at 12.6%. Outcomes may be improved if local recurrence is reduced at the most common sites such as the peri-anastomotic area or peritoneum. Extra-nodal CT-imaging biomarkers of local peritoneal infiltration and tumour deposits were prognostically significant on multivariate analysis in addition to pathology staging variables.     

Aberrant crypts: putative preneoplastic foci in human colonic mucosa

Aberrant crypts were identified for the first time in whole-mount preparations of normal-appearing human colonic mucosa after staining with methylene blue. The foci of aberrant crypts varied from single altered glands to plaques of greater than 30 crypts. The mean proportion of colonic mucosa altered and the number of foci with aberrant crypts per cm2 of colonic mucosa were (a) higher in patients with colon cancer than in patients without colon cancer or predisposing conditions and (b) highest in our single case of Gardner's syndrome. Aberrant crypts are postulated to be the earliest identifiable potential precursors of colon cancer. Analysis of aberrant crypts may facilitate the study of the early pathological and molecular changes that precede colon cancer.     

Mucinous adenocarcinoma arising in a neovagina using the sigmoid colon thirty years after operation: a case report

BACKGROUND: Because of a relative rarity of the cases with an artificial vagina, the incidence of a case with malignant disease arising in the neovagina is extremely rare. A case of adenocarcinoma arising from a neovagina is presented with a review of the literature. CASE: A neovagina was constructed using the sigmoid colon at the age of 23 for congenital agenesis of the vagina, Rokitansky-Küster-Hauser syndrome. Subsequently, the patient had regular sexual intercourse for about 20 years. At the age of 53, she came to our outpatient clinic with a complaint of vaginal bleeding, and adenocarcinoma was found at the anterior wall of the neovagina adjoining the introitus. Total resection of the neovagina and adjuvant radiotherapy was performed. The pathological diagnosis was mucinous adenocarcinoma. CONCLUSIONS: In view of relatively low incidence of mucinous carcinoma arising in the sigmoid colon along with the ectopic localization, this case may have implications for the understanding of pathogenesis of sigmoid colon cancer.     

A case of advanced colon cancer invading the rectum effectively treated with chemoradiation therapy before surgery

A 56-year-old man was hospitalized for anemia with appetite loss and body weight loss. He was diagnosed as advanced sigmoid colon cancer which invaded the rectal colon (Ra) and prostate (SI, N 0, P 0, H 0, M (-), cStage IIIa).We administered neoadjuvant chemoradiotherapy for fear of non-curative resection of the sigmoid colon and rectum after colostomy was performed. He was given radiation of the whole pelvis at a total dose of 39 .6 Gy (1.8 Gy x 22 times) combined with chemotherapy using continuous intravenous 5-FU (500 mg x 22 times). Two weeks after the chemoradiation, we administered chemotherapy (FOLFOX 4). Resectable resection was confirmed on Computed Tomography. We were able to conduct a low anterior resection of sigmoid colon and rectum. Postoperative histopathological examination of the resected sigmoid colon and rectum revealed no remnant cancer tissue. Neo-adjuvant chemoradiotherapy is considered to be effective for a study of non-curative resection of rectum.     

Oncological outcome of carcinomas in the rectosigmoid junction compared to the upper rectum or sigmoid colon – A retrospective cohort study

IntroductionAlthough carcinomas of the rectosigmoid junction are frequent, specific data on these tumors are sparse because assignment either to the colon or rectum is common. The objective of this study is to determine whether carcinomas of the rectosigmoid junction can be assigned to the sigmoid colon or to the upper rectum in terms of tumor characteristics and oncological outcome.Materials and methods337 consecutive patients undergoing resection of carcinomas in the sigmoid colon, the rectosigmoid junction and the upper third of the rectum were analyzed retrospectively and additionally followed-up for oncological outcome.Results185 patients (54.9%) showed carcinoma in the sigmoid colon, 41 (12.2%) in the rectosigmoid junction and 111 (32.9%) in the upper rectum. Synchronous liver metastases (rectosigmoid junction 31.7%, sigmoid colon 16.2%, upper rectum 11.7%; P = 0.01), lymphovascular invasion (rectosigmoid junction 46.3%, sigmoid colon 25.4%, upper rectum 32.4%; P = 0.03) and pN2 (rectosigmoid junction 31.7%, sigmoid colon 10.3%, upper rectum 13.5%; P = 0.002) were more common in carcinomas of the rectosigmoid junction. The median follow-up period was 44 (22–75.5) months. Five-year overall survival was 44.6% in patients with carcinomas in the rectosigmoid junction, 70.9% in the sigmoid colon, and 70.2% in the upper rectum.ConclusionCarcinomas of the rectosigmoid junction reveal a deviant behavioral pattern compared to its adjacent bowel segments.     

A case of sigmoid colon cancer with multiple liver metastases responding to S-1

A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer.     

Abnormal sensitivity of skin fibroblasts from familial polyposis patients to DNA alkylating agents

Fibroblast cell strains derived from different patients all afflicted with genetic predisposing to the development of intestinal polyposis and cancer were tested for their sensitivity to the lethal effects of the DNA alkylating agents methylmethanesulfonate (MMS), ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline 1-oxide. The genetic syndromes studied were: (a) adenomatosis of the colon and rectum only, an autosomal dominant trait; (b) Turcot's syndrome, a rare autosomal recessive polyposis syndrome also characterized by central nervous system tumors; and (c) Gardner's syndrome, an autosomal dominant syndrome which, in addition to intestinal polyposis, is also clinically characterized by osteomas and soft tissue tumors. Survival (relative clone-forming ability) of the various polyposis fibroblast strains was compared to the average survival of three normal human fibroblast strains by t test analysis of the respective values for the inverse of the slope of the survival curve (D0) and the concentration resulting in 10% survival (D10) with p less than 0.05 considered significant. Fibroblasts from the patient with adenomatosis of the colon and rectum (strain GM2355) were moderately but significantly sensitive to 4-nitroquinoline 1-oxide with D0 and D10 values of 0.069 microM (p less than 0.05) and 0.15 microM (p = 0.01), respectively, compared with the normal values of 0.10 microM and 0.26 microM. In addition, strain GM2355 was significantly more sensitive to ethyl methanesulfonate based on D10 comparison only, 24 mM versus the normal average D10 of 28 mM (p less than 0.05). Fibroblasts from the patient with Turcot's syndrome were hypersensitive to MMS, having a D0 value of 0.24 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 value of 0.95 mM (p less than 0.01) compared with the normal average value of 1.3 mM. Fibroblasts from the Gardner's syndrome proband were moderately sensitive to MMS, ethyl methanesulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine due to significant differences of D10 values of 0.60 mM (p less than 0.01), 15 mM (p less than 0.01), and 4.8 microM (p less than 0.025), respectively, versus the normal average values of 1.3 mM, 28 mM, and 9.4 microM. Fibroblasts from the clinically affected Gardner's syndrome daughter of the proband were significantly more sensitive to MMS treatment, D0 of 0.22 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 of 0.97 mM (p less than 0.01) versus the normal average. This differential sensitivity to the several DNA alkylating agents suggests that different mechanisms of hypersensitivity to these chemicals may be associated with fibroblasts from the various forms of familial polyposis.     

Growing teratoma syndrome in a post laparoscopic excision of ovarian immature teratoma

A 26-year-old girl was referred to us in December 2008 with progressive pelvic mass while on chemotherapy. In May 2008, she presented with large adnexal mass and high alpha-fetoprotein (AFP, 265.7 ng/mL; normal range, 0 to 10). She underwent laparoscopic right salpingo-oophorectomy with staging. Since histology was immature teratoma grade I, FIGO stage 1 she was kept on surveillance. In September 2008, she developed recurrent pelvic mass with AFP levels of 2,400 ng/mL. Three courses of chemotherapy (bleomycin-etoposide-cisplatin) were given. Post-chemotherapy AFP normalized but tumor size increased. CT-scan (abdomen-pelvis) showed a large pelvic mass with calcification specks; infiltrating the sigmoid colon and abdominal wall. With provisional diagnosis of growing teratoma syndrome she had exploratory laparotomy with excision of pelvic mass along with sigmoid colon, excision of right pelvic and subcutaneous deposits, omentectomy and sigmoid anastomosis. Left ovary, left tube and uterus appeared normal and were preserved. Histology of all masses showed mature teratoma, no immature elements. At six months follow up she is disease free and has resumed menstruation. Growing teratoma syndrome is a clinico-pathological presentation during/post-chemotherapy in malignant ovarian germ cell tumor where mature teratoma grows and requires complete surgical excision. Our case highlights the safety and adequacy concerns of laparoscopic management of malignant ovarian tumor. Literature review suggests good prospects of resumption of menses, child bearing and five year survival in case of growing teratoma syndrome.     

Basic Science Review: A Multistage Model for Human Colon Carcinoma Development Integrating Cell Culture Studies with Pathology

There is much clinical and experimental evidence that colon carcinoma in humans evolves through a series of preneoplastic stages. Preneoplastic colonic cells have been characterized in normal-appearing epithelium of “flat mucosae” from patients genetically at risk to develop colon cancer. These cells differ from normal colonic epithelial cells by a delay in terminal differentiation which leads to an enlargement of the zone of dividing cells within the colonic crypt, a test-tube-like hollow cylinder roughly 50-60 cells deep (1,2). These patients include those with familial polyposis or Gardner's syndrome and those without polyposis, but with a family history of first-degree relatives with colon cancer. Such crypts with extended proliferative zones are not only characteristic of patients genetically predisposed to develop colon cancer, but are found in patients without any known syndrome who have developed a carcinoma (3). The biopsies were taken at least 4 cm from the tumor, suggesting an area of altered epithelial cells had arisen within the colon and that the carcinoma arose from some of these precursor cells. Supporting this interpretation is the finding that such abnormal crypts predate the appearance of adenomas and carcinomas in the dimethylhydrazine-induced model of colon carcinoma in CF, mice (3).     

A case of multiple liver metastases of sigmoid colon cancer responding well to UFT+Leucovorin therapy

The subject was a 75-year-old female. For the treatment of multiple liver metastases from sigmoid colon cancer, the administration of UFT(300 mg/day)and oral Leucovorin(75 mg/day)was initiated after a resection of the sigmoid colon. A decrease in the liver metastases was observed in a CT scan 4 months after the start of this administration, and the disappearance of the metastatic focus in the liver was confirmed at 10 months thereafter. The administration of UFT and oral Leucovorin was continued for 2 months. Thereafter, at 12 months after the start of this administration, was continued with only the administration of UFT(300 mg/day)for 1 year. Now, 26 months have passed since the liver metastases disappeared and no recurrence has been found, even within the abdominal cavity. The condition of the patient has been excellent. The subject of this study was an elderly person, but an excellent QOL was secured without any adverse events, and the chemotherapy regimen could be maintained for 2 years. These findings suggest that UFT and oral Leucovorin can be expected to have an excellent therapeutic effect as an oral chemotherapeutic agent.     

Advanced rectal cancer in an older patient, in whom metastatic liver lesions were effectively controlled with oral UFT+LV and venous CPT-11 administration--case report

An 81-year-old man was admitted to our department due to acute ileus. He was diagnosed with sigmoid colon cancer with multiple metastatic lesions in the right lobe of the liver. Two weeks after insertion of an ileus tube, he underwent sigmoidectomy and permanent colostomy. The final diagnosis was stage IV sigmoid colon cancer with metastasis to the omentum. One month after the operation, adjuvant chemotherapy with oral administration of tegafur/uracil compound (UFT) and Leucovorin (LV), and drip venous infusion of irinotecan hydrochloride (CPT-11) was initiated (UFT 300 mg/day for 14 days, LV 75 mg/day for 14 days, CPT-11 90 mg/m(2) on the 1 st day, with 1 course consisting of 21 days). The levels of tumor markers, CA19-9 and CEA, and the size of metastases on CT were reduced remarkably after one and 4 courses of this therapy, respectively. Although the administration was temporarily discontinued due to low-grade nausea, we continued the treatment. Adjuvant chemotherapy with an oral administering agent is favorable for older patients with advanced colorectal cancer to reduce side effects and preserve the quality of life.     

Colorectal cancer in pregnancy: a case report and literature review

Colorectal cancer (CRC) in pregnancy is rare. The clinical manifestations of CRC during pregnancy are not specific, and diagnosis and treatment pose a significant challenge. Patients are often found to have advanced tumors, and have a poor prognosis. In this case study, the patient was 36 years old, and had no obvious clinical manifestations in the first and second trimesters. Since gestational week 38, she experienced left upper abdominal pain and constipation, with no nausea or vomiting. Imaging examinations revealed malignant tumors of the sigmoid colon (colon cancer was highly suspected), multiple liver metastases, omental metastases, and multiple swollen lymph nodes in the abdominal cavity. After discussion, the patient received lower cesarean section. A large amount of hematochezia with a volume of approximately 1,000 mL occurred 8 days after the operation. In the emergency department, superior and inferior mesenteric angiography was performed, and the inferior mesenteric artery was continuously pumped with pituitrin to stop bleeding. After the condition was stabilized, she underwent surgery for radical sigmoid resection and colon single-cavity fistula. During the operation, light bloody ascites were observed inside the abdominal pelvis, approximately 500 mL, with multiple touchable stiff metastatic nodules in the liver. At the side of the sigmoid mesocolon, a giant tumor of approximately 12 cm diameter was found, continued by the intestinal wall, and the sigmoid mesocolon was almost occupied by the tumor. The mesentery was hard to recognize, with possible movement of the tumor, and no sign of infiltration into the abdominal pelvic wall or adnexa. The surgical pathological stage was Dukes’ stage D, which was an advanced tumor. Postoperative radiotherapy and chemotherapy were not performed, and the patient died of systemic multiple organ failure 32 days after colon cancer surgery (postpartum day 43). So for patients with digestive system symptoms during pregnancy, CRC should be considered in differential diagnosis. Auxiliary examinations should be actively carried out to strive early diagnosis and treatment to improve patient prognosis.     

The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.

The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine.     

A case of reversible posterior leukoencephalopathy syndrome(RPLS)induced by modified FOLFOX6

We report here a case of reversible posterior leukoencephalopathy syndrome(RPLS)induced by modified FOLFOX6(mFOLFOX6). The patient was a 43-year-old woman who had sigmoid colon cancer with multiple liver metastases. Treatment with mFOLFOX6 was started. Early in the morning of day 11, the patient was transported by ambulance to the hospital due to nausea with headache, disturbed consciousness, and visual disturbance. The patient experienced sudden, severe nausea and subsequently presented generalized tonic-chronic seizures. The seizures subsided after treatment. On the evening of day 11, another episode of generalized tonic-chronic seizures occurred. Status epilepticus developed and tracheal intubation was performed for airway protection. Cranial MRI showed increased signal intensity in both occipital lobes, centered on the boundary between the gray and white matter on FLAIR images. Her condition stabilized with no seizure recurrence following intubation. Although hypertension was present on admission to the emergency room, blood pressure gradually fell to within the normal range without antihypertensive treatment. She was extubated on day 18. There were no neurologic sequelae. Cranial MRI on day 40 showed that the increased intensity in both occipital lobes had almost disappeared. Because the patient's condition was characterized by a reversible central nervous system disorder, RPLS was diagnosed.     

Recreational physical activity and cancer risk in subsites of the colon (the Nord-Tr?ndelag Health Study).

Physical activity may reduce colon cancer risk, but the underlying mechanisms remain unclear. Relating physical activity to cancer risk in anatomic segments of the colon may advance our understanding of possible mechanisms. We conducted a prospective study of 59,369 Norwegian men and women who were followed up for cancer incidence and mortality. Cox proportional hazards models were used to estimate multivariably adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). All statistical tests were two sided. During 17 years of follow-up, 736 colon cancers and 294 rectal cancers were diagnosed. Overall, we found an inverse association between recreational physical activity and colon cancer risk, but subsite analyses showed that the association was confined to cancer in the transverse and sigmoid colon. The adjusted HR, comparing people who reported high versus no physical activity, was 0.44 (95% CI, 0.25-0.78) for cancer in the transverse colon and 0.48 (95% CI, 0.31-0.75) for cancer in the sigmoid colon. The corresponding HR for cancer mortality was 0.33 (95% CI, 0.14-0.76) for the transverse colon and 0.29 (95% CI, 0.15-0.56) for the sigmoid colon. For rectal cancer, there was no association with physical activity in these data. In conclusion, the inverse association of recreational physical activity with cancer risk and mortality in the transverse and sigmoid segments of the colon may point at increased colon motility and reduced fecal transit time as possible underlying mechanisms.     

A case of remarkable regression of a colonic cancer involving metastasis to the liver as a result of FT-207 treatment

In mid-August, 1986, a 50-year-old man underwent a detailed examination following the finding of a tumor in the upper abdominal region. The tumor was revealed to be a sigmoid colon cancer with multiple metastasis to both halves of the liver. Subsequent administration of FT-207 suppositories (750 mg X 2/day) resulted in a recognizable shrinkage of the metastatic lesions in the liver after one month, and a barium enema a month later indicated a decrease in the size of the original tumor. The pre-operative CEA value was 2,317 ng/ml, but this has reduced to 46.7 ng/ml to date March, 1987. In this report of single chemotherapy treatment with FT-207 of a sigmoid colon cancer involving metastasis to the liver, the prognosis obtained for the original and hepatic lesions has been good, and the patient's course to date healthy.     

Studies on the results of operations for carcinoma of the sigmoid colon

Of 734 patients with colorectal cancer operated on during the past 21 years, 142 had carcinoma of the sigmoid colon. Curative resections were performed in 103 patients and non-curative resections in 22, the resection rate being 88.0%. Among 103 patients with curative resection, resection of the sigmoid colon was performed in 79, and their 5-year survival rate was 84.6%. Eight patients died within 5 years due to recurrence. Many of them had the constricting type macroscopically and Dukes C with positive lymph node metastasis. Therefore, in such cases, resection of the sigmoid colon with extended lymph node dissection or left hemicolectomy should be performed.     

An Inflammatory Polyp of the Sigmoid Colon Observed in a Case with a Ruptured Ovarian Dermoid Cyst

We present here a rare case, an ovarian dermoid cyst with fistulaformation into the sigmoid colon, which forms an inflammatorypolyp of the sigmoid colon. A 58-year-old woman was admitted because of occasional analbleeding. Several examination disclosed the elevation of erythrocytesedimentation rate, a positive test of stool specimen for occultblood, a polyp of the sigmoid colon in barium enema. Laparotomyshowed that a dermoid cyst of the left ovary had ruptured intothe sigmoid. The etiology of the rupture was "idiopathic." Thefistulous communication between the cyst and the sigmoid colonwas thought to have developed the inflammatory polyp over aperiod of about two years.     

A case report--TS-1/CDDP combined chemotherapy found effective for metastatic recurrence after operation for colon cancer

A 68-year-old male with a history of gastric resection for gastric cancer underwent resection of the sigmoid colon for a sigmoid colon cancer in February, 2000. The cancer was classified as stage III b. After operation, l-LV + 5-FU therapy was administered, but metastases to the abdominal wall, right inguinal lymph node and spleen developed in succession, and resection was repeated. In October 2001, 1 year and 8 months after sigmoidectomy, however, multiple metastasis to the intraperitoneal lymph node had developed. As surgery was not indicated, TS-1/CDDP combined chemotherapy was started. TS-1 80 mg/day was administered for 4 weeks, the drug was withdrawn for 2 weeks and CDDP 80 mg was injected by intravenous drip at the 8th day of TS-1 administration, which was used as one course. From the second course after inception of the administration, CA19-9 decreased, and after the third course the upper intraperitoneal metastatic lesion disappeared on CT. CR has been continued for 4 months up to the present. Our results suggest a possibility that this therapy is effective not only for gastric cancer but also for colon cancer. This therapy can be administered at home. It is considered to be a useful therapy from the viewpoint of QOL as well. The high DPD activity of the tumor may have been one reason this treatment was effective. This case also seems significant from the viewpoint of attaining individualization of the drug selection in chemotherapy.