Curative Resection For Colorectal Carcinoma Research Articles

The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI. Between February and September 2023, two examinations were performed on 80 subjects within a period of 0-30 days and at two previously defined quality levels, aligned to the German standards of the DEGUM. Correlation analyses were carried out using Pearson's correlation coefficient (PCC) and the intraclass correlation coefficient (ICC). The diameters, blood flow, and DPI showed a high degree of agreement (PCC of 0.9 and ICC of 0.9 for AHP). Provided that a precise standard of procedure is adhered to, the Doppler examination of AHC, AHP, and PV yields very reproducible blood flows and DPI, which is a prerequisite for a comprehensive investigation of its prognostic value for the prediction of metachronous hepatic metastasis in the context of curatively treated CRC or PDAC.

Application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma

Objective: To investigate the clinical application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma. Methods: Patients diagnosed with colorectal cancer before operation and undergoing radical surgery with intact postoperative pathological data in the Sixth Affiliated Hospital, Sun Yat-sen University from March 2016 to March 2018 were included in this retrospective case-control study. Those who were diagnosed with ileus, recurrent carcinoma or underwent emergency operation were excluded. A total of 1421 cases were included, with 156 cases in the carbon nanoparticles mapping group and 1265 cases in the control group. Using 1∶3 case control matching based on gender, weight, TNM staging and neoadjuvant chemotherapy, 145 and 435 cases were finally recruited in the carbon nanoparticles mapping group and control group, respectively. Patients in the carbon nanoparticles mapping group underwent preoperative colonoscopy with carbon nanoparticles submucosal injection 2.4 (1.0 - 14.0) days before operation. Carbon nanoparticles of 0.25 ml was injected at 4 points (3, 6, 9 and 12 o'clock each) 0.5-1.0 cm around the tumor. The number of eliminated lymph node, number of positive lymph node and positive rate between the two groups were compared, and the number of eliminated lymph node in different subgroups of T stage, N stage, TNM stage and neoadjuvant chemotherapy was analyzed and compared. Results: After case control matching, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher than that in the control group (22.2±11.2 vs. 19.0±9.5, t=3.025, P=0.003). However, no statistically significant differences were found in the number of positive lymph node and lymph node positive rate between two groups (all P>0.05). Subgroup analysis showed that as compared to the control group, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher in T3 stage subgroup (median: 22 vs. 18, Z=2.435, P=0.015), N0 stage subgroup (median: 20.5 vs. 17.5, Z=2.772, P=0.006), TNM II stage subgroup (median: 23.5 vs. 19.0, Z=2.654, P=0.008) and neoadjuvant chemotherapy (median: 22.5 vs. 13.0, Z=3.287, P=0.001), while compared to the control group, the number of positive lymph node (median: 4.0 vs. 6.5, Z=-2.530, P=0.011) and the lymph node metastasis degree (median: 16% vs. 31%, Z=-2.862, P=0.004) were lower in the carbon nanoparticles mapping group in N2 subgroup. Conclusion: Carbon nanoparticles mapping lymph nodes can effectively enhance the number of eliminated lymph nodes in curative resection for colorectal cancer.

Clinical application of carbon nanoparticles in curative resection for colorectal carcinoma.

PurposeTo explore the potential of carbon nanoparticles (CNs) for the intraoperative detection of positive and negative lymph nodes in the treatment of colorectal cancer.Patients and methodsThe clinical data of 470 patients undergoing surgical procedures for colorectal cancer from June 2010 to February 2013 were analyzed retrospectively. The patients were divided into the CN group (183 males and 161 females; mean age, 58.6±12.4 years), who were given a CN suspension, and the control group (78 males and 48 females; mean age, 59.1±12.2 years), who were not given a CN suspension. The operative time, blood loss, number of lymph nodes detected/positive lymph nodes, and prevalence of postoperative complications were compared between the two groups. Three years after surgery, 444 cases (327 cases in the CN group and 117 cases in the control group) were interviewed, with the remaining 26 cases lost to follow-up. With regard to tumor, node, metastasis staging, the survival and prevalence of recurrence in each group at 3 years were analyzed.ResultsThe number of positive lymph nodes was higher and the prevalence of blood loss was lower in the CN group than in the control group (p<0.05). There were no significant differences in the operative time, number of lymph nodes detected, or the prevalence of postoperative complications, survival, metastasis, or recurrence between the two groups at 3 years (p>0.05).ConclusionThe application of CNs is convenient for the detection of lymph nodes to reduce blood loss and increase the probability of detecting positive lymph nodes accurately and rapidly.

Results of Adjuvant FOLFOX Regimens in Stage III Colorectal Cancer Patients: Retrospective Analysis of 667 Patients

Objective: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. Methods: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. Results: The median age of the patients was 56 years (range 17–78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1–79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. Conclusion: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Adherence to national guidelines for surveillance after curative resection of nonmetastatic colon and rectum cancer: a survey among Norwegian gastrointestinal surgeons

National guidelines recommend enrollment of patients in surveillance programmes following curative resection of colorectal carcinoma (CRC) in order to detect recurrence or distant metastasis at an asymptomatic/early stage when secondary curative treatment can be offered. Little is known about surgeons' adherence to such guidelines. In this national survey we analyse adherence and attitudes to postoperative follow up among Norwegian gastrointestinal surgeons involved in the care of patients with CRC. We performed a nationwide survey of all hospitals performing surgery for colon and/or rectum cancer. The presence of a surveillance programme, the type of programme, adherence to national guidelines or report on any deviation thereof, location of follow up at the hospital or with a general practitioner (GPs) and the estimated annual volume of surgery were queried through mail and telephone. All hospitals (n=41) performing colorectal surgery responded, of which 25 (61%) conducted postoperative follow up by surgeons in the hospital outpatient clinics, four (10%) carried out follow up with a combination of hospital outpatient visits and visits to GPs, and 12 (29%) referred surveillance to the GP alone. For total reported patient numbers, almost two-thirds (60%) received surveillance according to national recommendations through outpatient visits with the surgeon or GP, while one-third (37%) were subject to other alternative routines. A small number (2%) received informal 'ad hoc' surveillance only. More liberal use of imaging outside guideline recommendations was reported for rectal cancer patients, while colon cancer patients treated in larger hospitals were more likely to be referred for GP surveillance. All hospitals reported having a strategy for surveillance after surgery for colon and rectal cancer, but there was considerable variance in strategy. A scientific audit of the true level of compliance, effectiveness and cost-benefit is warranted at a national level.

Conversion in Laparoscopic Colorectal Cancer Surgery: Impact on Short- and Long-Term Outcome

Despite the well-documented safety and effectiveness of laparoscopic colorectal surgery in curative intention, the role of conversion and its impact on short- and long-term outcome after resection of a carcinoma are unclear and continue to give rise to controversial discussion. Within the framework of a prospective, multicenter observational study (Laparoscopic Colorectal Surgery Study Group), into which a total of 5,863 patients from 69 hospitals were recruited over a period of 10 years, a subgroup of all patients who had undergone curative resection was analyzed with regard to the effects of conversion. Of the 1409 patients who had undergone curative resection for colorectal carcinoma, conversion had to be performed in 80 (5.7%) cases for the most diverse reasons. The duration of surgery (median: 183 vs. 241 minutes; P<.001) was significantly longer in the conversion group. Perioperatively, significant disadvantages were noted in converted patients in terms of intraoperative blood loss (median: 243 vs. 573 mL, P<.001), need for perioperative blood transfusion (10.8% vs. 33.8%; P<.001), and resumption of bowel movement (median: after 3 vs. 4 days; P<.001). With regard to postoperative morbidity, significant disadvantages were observed in converted patients, in particular in terms of specific surgical complications, including a higher rate of anastomotic insufficiency (5.0% vs. 13.8%; P=.003) and a higher reoperation rate (4.9% vs. 15.0%; P=.001). In the long term, conversion was associated with lower overall survival, but not with poorer disease-free survival. Significantly higher postoperative morbidity was observed in patients after conversion, in particular in terms of specific surgical complications. In addition, conversion is associated with overall lower survival but not with poorer disease-free survival.

First Alert for Recurrence During Follow-up After Potentially Curative Resection for Colorectal Carcinoma: CA 19-9 Should Be Included in Surveillance Programs

The aim of this study was to evaluate the contribution of each examination included in the postoperative surveillance program, especially that of serum tumor markers. Patients who underwent curative surgery for colorectal carcinoma (CRC) from January 2000 to December 2006 were enrolled. The postoperative surveillance program in our department includes tumor marker (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 19-9) measurement every 3 months for 5 years, chest radiograph or chest computed tomography (CT) every 3 months for 2 years and then every 6 months until 5 years, and abdominal CT every 3 months for 2 years and then every 6 months until 5 years. The first examination that revealed abnormality in patients who developed recurrence was analyzed. During the study period, 105 recurrences were diagnosed. There were 45 hepatic recurrences, 23 local recurrences, 20 pulmonary recurrences, 16 lymph node recurrences, and 10 peritoneal recurrences. Computed tomography, CEA, and CA 19-9 were the first abnormal examination(s) in 77, 23, and 26 patients, respectively. Tumor markers detected the recurrence earlier than did CT in 27% of patients. CEA and CA 19-9 equally contributed to detection with respect to the number of patients, while the sites of detected recurrences differed. For early detection of occult recurrence of CRC, CT was the most reliable modality. On the other hand, tumor markers were also relevant. Given the recent advances in multimodal approaches for advanced CRC, the combination of CT, CEA, and CA 19-9, which is currently not included in guidelines, should be routinely performed.

Yield of Routine Imaging after Curative Colorectal Cancer Treatment

Background-aim : The use of imaging in the follow-up of patients after curative colorectal cancer resection is much debated. The American Society of Colon and Rectal Surgeons did not recommend routine imaging. This retrospective study assesses the yield of routine imaging to detect recurrent disease.Methods : In 1998, 108 consecutive patients underwent curative resection for colorectal carcinoma. Minimum follow-up in our institution was 3 years. Multidisciplinary follow-up at a joint clinic consisted out of a history, clinical examination, serum carcinoembryonic antigen (CEA), chest X-ray and abdominal ultrasound, at least every 6 months. Colonoscopy was performed within 1 year after operation and every 3 to 5 years thereafter. The incidence, timing, means of detection and resectability of recurrence were studied.Results : The recurrence rate was 22% (24 patients): liver metastases (11), extra-hepatic recurrence (10) and combined recurrence (3). Recurrent disease occurred in stage II or III cancer, except for two patients. It was diagnosed at a median of 21.5 months (range 4–79) after surgery. Means of detection were: symptoms in 2 (peritoneal disease, 8%), increasing CEA in 15 (63%), routine imaging in 6 (25%), and abdominal CT-scan in one patient. Curative resection of recurrent disease was possible in ten patients (42%): in 6/15 recurrences detected by CEA, in 3/6 recurrences detected by routine imaging, in 1 liver metastasis detected by CT and in none of the symptomatic patients. Conclusions : A CEA level increasing above 5.0 μg/L was the most important diagnostic tool. However, one quarter of the recurrences were detected by routine imaging and half of them could be resected for cure. These data support routine imaging during follow-up.

Isolated paraaortic lymph‐node recurrence after the curative resection of colorectal carcinoma

Isolated paraaortic lymph-node recurrence (IPLR) after curative surgery for colorectal carcinoma is rare and no previous report has specifically addressed this type of recurrence. We investigated the clinical features of IPLR and analyzed prognostic factors. Of 2,916 patients who underwent curative surgery for colorectal carcinoma, IPLR was identified in 38 patients (1.3%). The clinical features and prognostic factors of these patients were analyzed. IPLR was first detected by increased serum carcinoembryonic antigen (CEA) levels (63.2%) or by routine follow-up computed tomography (CT) (36.8%). Curative resection of IPLR was performed in six patients (15.8%). A total of 19 patients (50.0%) received chemoradiation therapy and 13 patients (34.2%) received chemotherapy only. The median survival from IPLR was 13 months (range: 5-60 months). The median survival time from IPLR for the resected patients was 34 months, whereas it was 12 months for those who did not undergo resection (P = 0.034). The factors associated with the prognosis were histological grade (P = 0.003), location (P = 0.032), and resection of IPLR (P = 0.034). IPLR after curative surgery for colorectal carcinoma is rare. Although it is generally associated with poor prognosis, better survival might be achieved through curative resection in selected cases.

Results of a national survey among Dutch surgeons treating patients with colorectal carcinoma. Current opinion about follow‐up, treatment of metastasis, and reasons to revise follow‐up practice

Follow-up after curative resection of colorectal carcinoma (CRC) has been subjected to debate concerning its effectiveness to reduce cancer mortality. Current national and international guidelines advise CEA measurements every 3 months during 3 years after surgery. The common clinical practice and opinion about follow-up for colorectal carcinoma, was evaluated by means of a survey among Dutch general surgeons. A web-based survey of follow-up after treatment of CRC was sent to all registered Dutch general surgeons. A reply from 246 surgeons treating patients for colorectal carcinoma in 105 out of 118 hospitals was received (response rate 91%). Questions related to actual follow-up protocol, opinion about serum CEA monitoring, liver and/or lung metastasectomy, and motivation to participate in a new trial concerning follow-up. For the majority of surgeons the length of follow-up was influenced by age of the patient (62%) and physical condition (76%) prohibiting hepatic metastasectomy. The generally accepted follow-up protocol consisted of CEA measurements every 3 months in the first year and six-monthly thereafter, and ultrasound examination of the liver every 6 months. Nearly all surgeons (92%) were willing to participate in a new study of follow-up protocol. The adherence to national guidelines for the follow-up of colorectal carcinoma is low. The indistinctness about follow-up after curative treatment of colorectal carcinoma also affects clinical practice. Recent advancements in imaging techniques, liver and lung surgery have changed circumstances, which are not yet anticipated upon in current guidelines. Renewal of follow-up based upon scientific evidence is required.

Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial

Background Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. Method Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n = 1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. Results Normal pre-operative CEA values were present in 63% (CEA < 5.0) and 39% (CEA < 2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA < 5.0), 50% (CEA < 2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. Conclusion A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

Occult hepatic metastases in colorectal carcinoma.

Occult hepatic metastases (OHMs) were detected by ultrasound and/or CT scanning in 17 of 71 (24 per cent) patients undergoing apparently curative resection for colorectal carcinoma. One of the patients with OHMs survived 5 years; in contrast, only 5 of 54 patients without evidence of OHMs at surgery died of disseminated disease. The presence or absence of OHMs at the time of surgery predicts the majority of deaths from disseminated disease following apparently curative resection for colorectal carcinoma.

The identification of patients at high risk following curative resection for colorectal carcinoma.

Thirty-five consecutive patients undergoing apparently curative resection for colorectal carcinoma were staged by conventional methods (Dukes', degree of tumor differentiation and pre- and postoperative CEA). In addition, the presence or absence of occult hepatic metastases at the time of surgery was determined by sequential CT scanning. Thirteen patients died within 30 months of surgery. Conventional prognostic indices failed to define clearly those patients who died. In contrast, the presence or absence of occult hepatic metastases at the time of surgery clearly defined two groups of patients. Only 9 per cent of patients who possessed occult hepatic metastases survived 30 months compared with 88 per cent of patients in whom these metastases were not detected. The clinical implications of these results are discussed.

The value of intensive follow-up after curative resection for colorectal carcinoma.

A previous study undertaken by this department showed follow-up to be of little value in tracing curable recurrences in patients with colorectal cancer who had curative operations. The aim of the present investigation was to determine if more intensified follow-up would result in earlier diagnosis of recurrences and thus lead to earlier and more effective treatment. Altogether 599 patients with colorectal cancer were treated between 1973 and 1977. The 363 (61 per cent) patients who were operated upon for cure entered the study and were followed up until December 1979. The same incidence of recurrence was seen in both series, but, with the more detailed protocol, they were more frequently detected before symptoms developed. However, the rate of curative reoperation for recurrence was not changed and only few patients survived after such reoperations. The conclusion is that the previous protocol is as efficient as the detailed one while no effective treatment of disseminated disease exists.

Pre-operative carcino-embryonic antigen and survival in patients with colorectal cancer.

The relationship between pre-operative levels of carcino-embryonic antigen (CEA), resectability of the primary tumour, the extent of tumour spread and subsequent survival was studied in 333 patients with colorectal cancer. Twenty-five per cent of patients undergoing 'curative' resection had elevated CEA levels compared with fifty-six per cent of patients receiving palliative treatment. Twenty-five per cent of patients with Dukes B or C tumours had elevated pre-operative CEA levels compared with seventy per cent of patients with stage D disease. In patients undergoing 'curative' resection there was no correlation between pre-operative CEA levels and subsequent survival. In patients undergoing palliative resection, elevated pre-operative CEA levels were associated with poor survival. Although pre-operative levels of CEA reflect the extent of the underlying disease process, estimations of pre-operative CEA levels are of limited value in predicting patients with a poor prognosis following curative resection for colorectal carcinoma.

Clinical significance of Ki-67 proliferation index in disease progression and prognosis of patients with resected colorectal carcinoma

The prognostic role of proliferation markers in patients with colorectal neoplasia is inconclusive. The aim of this study was to evaluate proliferation markers in patients with colorectal carcinoma, to relate these to standard clinicopathological findings and to investigate their potential role in the prediction of long-term survival. Archived formalin-fixed, paraffin-embedded tissue samples from a cohort of 106 patients who underwent curative resection for colorectal carcinoma were analysed to determine a Ki-67 (MIB-1)-derived proliferation index (PI) using a double immunostaining technique. The relationship between PI and standard clinicopathological variables was assessed and its association with long-term survival evaluated. A significant association was found between PI and tumour (T) status (P = 0.001), lymph node (N) involvement (P = 0.0098), the presence of distant metastases (P < 0.010) and advanced stage of disease (P < 0.001). On multivariate analysis, PI was shown to be an independent prognostic factor for long-term survival (hazard ratio 2.1 (95 per cent confidence interval 1.1 to 4.1); P = 0.032). Cell proliferation is significantly associated with tumour progression and may be used to identify patients with a predicted adverse outcome after resection of colorectal carcinoma.

Surgery promotes implantation of disseminated tumor cells, but does not increase growth of tumor cell clusters

Local recurrence and peritoneal dissemination is common after intentionally curative resection of colorectal carcinoma. It is not yet clear which mechanisms stimulate post-operative intra-abdominal tumor development. Enhanced adhesion or growth of tumor cells and/or post-operative immuno suppression may influence tumor recurrence. In the present study, we evaluated effects of local and remote surgery on intra-abdominal tumor development. A standardized intra-abdominal trauma was inflicted by rubbing both uterus horns in laparotomy groups, while a dorsolateral thoracotomy was performed in thoracotomy groups (on day -1, 0, or +3). To induce tumor development rats were injected intra-peritoneally with the coloncarcinoma cell line CC531s on day 0 and evaluated after 21 days. Rats undergoing laparotomy and injection on day 0 showed significantly higher tumorload than control rats (195 +/- 20 vs. 47 +/- 29, P < 0.001). When a laparotomy was performed, the day before tumor inoculation even higher tumorload was seen (245 +/- 37 vs. 195 +/- 20, P < 0.01). Strikingly, performing a thoracotomy on the day before or on the same day as tumor inoculation resulted in enhanced tumorload compared to controls as well (135 +/- 84 vs. 47 +/- 29; P < 0.001 and 88 +/- 38 vs. 47 +/- 29; P < 0.02, respectively). Either laparotomy or thoracotomy 3 days after tumor cell inoculation did not affect growth of pre-existing tumor cell clusters. The (post) surgical intra-peritoneal microenvironment enhances successful implantation of spilled tumor cells, whereas growth of adhered tumor cell clusters is not affected. The inflammatory response as a result of remote surgery promotes successful tumor development as well.

Oncological quality and preliminary long-term results in laparoscopic colorectal surgery

Our aim here was interpret data on the perioperative course, oncological quality, and preliminary long-term results of laparoscopic colorectal surgery carried out with a curative intent. The data were collected within the framework of a prospective multicenter observational study that has been ongoing since 1 Aug 1995 and includes 46 hospitals. Of a total of 3133 patients, 826 (26.4%) underwent a curative resection for colorectal carcinoma. The average age of the patients was 67.9 years; the sex distribution was almost 1:1. UICC staging of tumors (stages I, II, and III) showed the following figures: 301/36.4%, 265/32.1%, and 260/31.5%. In the majority of cases, an oncologically radical resection with high transection of the supplying vessels was performed. Intraoperative seeding of tumor cells was reported in 1.8% of the patients. In eight cases, the seeding was due to spontaneous rupture of the tumor. A mean of 13.5 lymph nodes in the resected specimen were investigated histopathologically (10.9 lymph nodes in stage I, 15 each in stages II and III). Depending on the individual hospital, we found a remarkable variation in the number of lymph nodes investigated. With a mean follow-up period of 2.1 years, Kaplan-Meier survival function showed acceptable results, both for rectal and colonic carcinoma, in comparison with conventional colorectal surgery. A stage-related consideration of the survival data yielded similar results. All in all, the results show that a laparoscopic colorectal procedure can meet oncological radicality criteria, even though certain reservations-in particular, in the case of procedures done with a curative intent-have not been completely eliminated.

Long-term prognostic value of conventional peritoneal cytology after curative resection for colorectal carcinoma.

This study was undertaken to evaluate the long-term prognostic significance of conventional peritoneal cytology in patients with advanced colorectal carcinoma after curative resection. A review was performed of 189 patients who underwent curative resection for pT3/T4 carcinoma of the colon and upper/middle rectum between March 1987 and December 1991. Patient outcomes were reviewed retrospectively. Peritoneal cytology was performed before manipulation of the tumor. Intraoperatively, 50 ml of saline were instilled and 20 ml were reaspirated for cytology. In all patients, Papanicolaou and Giemsa stainings were performed to detect intraperitoneal free tumor cells. The median follow-up was 103 months. Malignant cells were identified in peritoneal washings from 11 patients (5.8%). Of the 11 patients with positive cytology, six (54.5%) developed recurrence and peritoneal recurrence was observed in four (36.4%). In contrast, of the 178 patients with negative cytology, 46 (25.8%) developed recurrence and peritoneal recurrence was observed in four (2.2%). The peritoneal recurrence rate was significantly increased (P = 0.0004) in the patients with positive cytology. The cancer-specific 10-year survival rates for the patients with positive and negative cytology were 45.5 and 80.3%, respectively (P = 0.0051). Multivariate analysis (Cox proportional hazard model) revealed that peritoneal cytology (positive: P = 0.0256) and lymph node metastasis (pN2: P = 0.0004) were independent predictors of cancer-specific survival. Conventional peritoneal cytology serves as a new prognostic marker after curative resection in patients with advanced colorectal carcinoma. It appears to be a useful diagnostic procedure for predicting recurrence, especially peritoneal recurrence.

K-ras Mutational Analysis of Polyclonal Colorectal Cancers Identifies Uniclonal Circulating Tumor Cells

The clonal development of colorectal carcinoma resulting from specific mutations in certain oncogenes and/or tumor suppressor genes is a well-accepted model. It is increasingly recognized that a majority of colorectal cancers are polyclonal on the basis of molecular analysis that demonstrates cells with different mutations within a given oncogene or tumor suppressor gene in the same tumor. This polyclonal pattern may occur as a result of either clonal convergence or divergence during the many steps of oncogenesis. Further complicating this picture is the fact that metastatic lesions may arise from only one of the clonal populations within a tumor and thereby present only a partial molecular make-up of the whole tumor. There are few data available that define clonal selection or specificity of circulating tumor cells in patients undergoing curative resection of colorectal carcinoma. The purpose of this paper is to describe the clonal distribution of circulating tumor cells in four patients with multiple K-ras mutations present in the primary lesion. Patients were selected who were known to have polyclonal primary colorectal cancers resected for cure. All patients had multiple mutations present in exon one, codon 12 and/or 13, of the K-ras gene. Blood samples were drawn immediately before surgery and at 2-week to 6-month intervals postoperatively. Epithelial cells were isolated from peripheral blood mononuclear cells using Dynal Immunobeads coated with antiepithelial antibodies. DNA was extracted from these cells and analyzed for all K-ras mutations present in codons 12 and 13 of the patient's primary tumor using allele-specific polymerase chain reaction followed by Microwell Array Diagonal Gel Electrophoresis. Circulating tumor cells were identified in all four patients. However, in each case of positive circulating cells the only mutation identified was an aspartic acid mutation at codon 13. Once positive the circulating tumor cells persisted in subsequent multiple blood samples. These results provide further strength for the theory of polyclonal progression in primary colorectal cancers, although there may be specific mutational patterns that confer the ability to metastasize. The significance of this persistence of the glycine-to-aspartic acid mutation at codon 13 remains to be defined given that none of these patients has clinical evidence of recurrent cancer at the time of this report.