Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

Effectiveness of a multidisciplinary patient care bundle for reducing surgical-site infections.

BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.

Incisional hernias after laparoscopic and robotic right colectomy.

PURPOSE: Incisional hernia (IH) is a common complication after colectomy, with impacts on both health care utilization and quality of life. The true incidence of IH after minimally invasive colectomy is not well described. The purpose of this study was to examine IH incidence after minimally invasive right colectomies (RC) and to compare the IH rates after laparoscopic (L-RC) and robotic (R-RC) colectomies. METHODS: This is a retrospective review of patients undergoing minimally invasive RC at a single institution from 2009 to 2014. Only patients undergoing RC for colonic neoplasia were included. Patients with previous colectomy or intraperitoneal chemotherapy were excluded. Three L-RC patients were included for each R-RC patient. The primary outcome was IH rate based on clinical examination or computed tomography (CT). Univariate and multivariate time-to-event analyses were used to assess predictors of IH. RESULTS: 276 patients where included, of which 69 had undergone R-RC and 207 L-RC. Patient and tumor characteristics were similar between the groups, except for higher tumor stage in L-RC patients. Both the median time to diagnosis (9.2 months) and the overall IH rate were similar between the groups (17.4 % for R-RC and 22.2 % for L-RC), as were all other postoperative complications. In multivariable analyses, the only significant predictor of IH was former or current tobacco use (hazard raio 3.0, p = 0.03). CONCLUSIONS: This study suggests that the incidence of IH is high after minimally invasive colectomy and that this rate is equivalent after R-RC and L-RC. Reducing the IH rate represents an important opportunity for improving quality of life and reducing health care utilization after minimally invasive colectomy.

Prognostic aspects of DCE-MRI in recurrent rectal cancer.

OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.

Goblet cell carcinoid neoplasm of the appendix: clinical and CT features.

PURPOSE: To describe the clinical and CT imaging features of goblet cell carcinoid (GCC) neoplasm of the appendix. METHODS AND MATERIALS: A computer search of pathology and radiology records over a 19-year period at our two institutions was performed using the search string "goblet". In the patients with appendiceal GCC neoplasms who had abdominopelvic CT, imaging findings were categorized, blinded to gross and surgical description, as: "Appendicitis", "Prominent appendix without peri-appendiceal infiltration", "Mass" or "Normal appendix". The CT appearance was correlated with an accepted pathological classification of: low grade GCC, signet ring cell adenocarcinoma ex, and poorly differentiated adenocarcinoma ex GCC group. RESULTS: Twenty-seven patients (age range, 28-80 years; mean age, 52 years; 15 female, 12 male) with pathology-proven appendiceal GCC neoplasm had CT scans that were reviewed. Patients presented with acute appendicitis (n=12), abdominal pain not typical for appendicitis (n=14) and incidental finding (n=1). CT imaging showed 9 Appendicitis, 9 Prominent appendices without peri-appendiceal infiltration, 7 Masses and 2 Normal appendices. Appendicitis (8/9) usually correlated with typical low grade GCC on pathology. In contrast, the majority of Masses and Prominent Appendices without peri-appendiceal infiltration were pathologically confirmed to be signet ring cell adenocarcinoma ex GCC. Poorly differentiated adenocarcinoma ex GCC was seen in only a small minority of patients. Hyperattenuation of the appendiceal neoplasm was seen in a majority of cases. CONCLUSIONS: GCC neoplasm of the appendix should be considered in the differential diagnosis in patients with primary appendiceal malignancy. Our cases demonstrated close correlation between our predefined CT pattern and the pathological classification.

Multivisceral resections for rectal cancer.

BACKGROUND: En bloc resection of adjacent pelvic organ(s) may be needed to achieve clear surgical margins in rectal cancer surgery. An institutional experience is reported with perioperative morbidity and oncological outcomes. METHODS: Patients were identified retrospectively from a prospectively collected institutional database (1992-2010). Outcomes, and clinical and pathological factors were determined from medical records. Estimated overall survival, overall recurrence and local recurrence were compared using the log rank method and Cox regression analysis. RESULTS: Among 1831 patients with rectal cancer, 124 (6·8 per cent) underwent en bloc resection of part or all of an adjacent organ (vagina/uterus/ovary 90, prostate/seminal vesicle 23, bladder/ureter 15, small bowel/appendix 7). Five-year overall survival and local recurrence rates were 53·3 and 18·8 per cent respectively. There was one postoperative death, from multiple organ failure in a patient with liver cirrhosis. Fifty-two patients underwent sphincter-preserving surgery and three (6 per cent) developed an anastomotic leak. On univariable analysis, the only factor associated with local recurrence was completeness of resection (local recurrence rate 15 per cent versus 69 per cent for R0 versus R1 resection; P < 0·001). On multivariable analysis, factors associated with overall survival were sphincter-preserving surgery, absence of metastatic disease and R0 resection. CONCLUSION: Multiple organ resection for locally advanced primary rectal cancer had good oncological outcomes when clear resection margins were achieved.

Extended surgery and pelvic exenteration for locally advanced rectal cancer. What are the limits?

Historically, locally advanced rectal cancers with invasion of tumor into adjacent organs (T4 N1, 2 tumors) have been considered poor prognosis cancers treated with palliative intent. However with the advent of multi-modality therapy and improvement in surgical reconstructive techniques, extended resections for rectal tumors are possible with acceptable patient morbidity and excellent oncological outcomes.

Young age influences treatment but not outcome of colon cancer.

BACKGROUND: Early age at onset is often considered a poor prognostic factor for colon cancer. The aim of this study was to determine the association between age, clinicopathologic features, adjuvant therapy, and outcomes following colon cancer resection. METHODS: A prospective database of 1,327 surgical stage I-III colon cancer patients operated on from 1990-2001 was evaluated, and patients grouped by age. RESULTS: Sixty-eight patients (5%) were diagnosed at age 40 (older). Younger patients were more likely to have left-sided tumors (66% vs 51%, P = .02), but no more likely to present with symptomatic lesions, more advanced tumors, or have worse pathologic features. Younger patients were noted to have more nodes retrieved in their surgical specimens than older patients (median 18 vs 14, P = .001), although the numbers of total colectomies were similar in both groups. Younger patients were also more likely to receive adjuvant chemotherapy, and this was most pronounced in the stage II cohort: 39% vs 14%, P = .003. With a median follow-up of 55 months, 5-year disease-specific survival (DSS) was similar in both study groups: 86% vs 87%, but 5-year overall survival (OS) was significantly higher in the younger patient cohort (84% vs 73%, P = .001). CONCLUSION: Younger patients undergoing complete resection of stage I-III colon cancer had DSS similar to older patients. However, younger patients had more nodes retrieved from their specimens and were more likely to receive adjuvant therapy, especially for node-negative disease. These factors may have contributed to their overall favorable outcome.

Preoperative evaluation and postoperative follow-up for patients with rectal cancer.

Rectal cancer has a wide variety of presentations. In most cases, it is the surgeon who is faced with the challenge of determining the extent of disease and advising the patient how to proceed with treatment. Utilizing diagnostic tests of the highest accuracy and relevance will help in the selection of the best initial therapy, which is critical for achieving the highest cure rate while also avoiding over-treatment and unnecessary morbidity. Following curative treatment, surveillance testing for detection of recurrence is traditionally done, but the efficacy of this practice has been questioned. Surveillance will detect a number of asymptomatic recurrences that are treatable by potentially curative salvage surgery, but to what extent early detection improves salvage therapy is not well established. In this brief review, the goals, methods, and expected benefits of rectal cancer staging and surveillance are assessed.

Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer.

PURPOSE: In a series of hereditary nonpolyposis colorectal cancer (HNPCC) patients, we evaluated the sensitivities of the individual microsatellites recommended by the National Cancer Institute (NCI) consensus workshop for detection of high-frequency microsatellite instability (MSI-H). On the basis of this evaluation, we developed a three-marker assay that assigns microsatellite instability (MSI) in a multiplex polymerase chain reaction. METHODS: Individual marker sensitivity was assessed in 18 HNPCC tumors. Multiplex and NCI assays were then assessed in a series of 120 patients with early-onset colon cancer. RESULTS: The sensitivity of microsatellite markers BAT25, BAT26, D2S123, D5S346, and D17S250 for ASI in HNPCC cancers was 100%, 94%, 72%, 50%, and 50%, respectively. The three most accurate markers were combined and optimized in a multiplex assay that assigned MSI-H whenever at least two of three markers revealed ASI. In early-onset colon cancers, the prevalence of MSI-H determined by the multiplex assay and by the NCI assay was 16% and 23%, respectively. The additional MSI-H tumors and patients with MSI-H identified by the NCI assay lacked the traits characteristic of MSI-H seen in tumors and patients identified by the multiplex assay: retention of heterozygosity (NCI additional 22% v multiplex 84%; P =.003), characteristic tumor morphology (0% v 64%; P =.006), and 5-year cancer survival rate (44% v 100%; P =.0003). CONCLUSION: The multiplex assay identifies colon cancers with MSI-H by assessing three highly accurate microsatellite markers. This assay identifies a smaller MSI-H cohort with more homogeneous clinical features and is superior as a marker of favorable prognosis. It merits prospective evaluation as a marker of prognosis and as a screening test for HNPCC.

Results after rectal cancer resection with in-continuity partial vaginectomy and total mesorectal excision.

BACKGROUND: Although sharp mesorectal excision reduces circumferential margin involvement and local recurrence, a concomitant partial vaginectomy may be required in women with locally advanced rectal cancer. METHODS: Sixty-four patients requiring a partial vaginectomy during resection of primary rectal cancer were identified. Survival was determined by the Kaplan-Meier method, and distributions were compared by the log-rank test. RESULTS: Locally advanced disease was reflected by presentation with malignant rectovaginal fistulae (n = 6) or cancers described as bulky or adherent/tethered to the rectovaginal septum (n = 32). Thirty-five patients received adjuvant radiation with or without chemotherapy. At a median follow-up of 22 months, 27 (42%) patients developed recurrent disease, with most of these occurring at distant sites. The 5-year overall survival was 46%, with a median survival of 44 months. The 2-year local recurrence-free survival was 84%. The crude local failure rate was 16% (10 of 64), and local recurrence was more common in patients with a positive as opposed to a negative microscopic margin (2 [50%] of 4 vs. 8 [13%] of 60, respectively). Positive nodal status had a significant effect on overall survival (P <.001). CONCLUSIONS: Partial vaginectomy is indicated for locally advanced rectal cancers involving the vagina. The results are most favorable in patients with negative surgical margins and node-negative disease.

Resection of locally recurrent colorectal cancer in the presence of distant metastases: can it be justified?

BACKGROUND: We aimed to determine the outcome of resections for local recurrence of colorectal carcinoma in the presence of distant (M1) disease. METHODS: Patients who underwent resection of local recurrence in the presence of potentially resectable M1 disease were identified from the colorectal database. Outcome was determined by chart review. RESULTS: Forty-two patients (23 men) of mean age 60 years (range, 34-88 years) underwent complete gross resection of their local recurrence in the presence of M1 disease. Thirteen of the 42 underwent synchronous M1 resections to render them free of gross disease (R0). Nine of the 29 patients who left with residual disease (R1) subsequently underwent staged M1 resection, so that 22 of 42 were rendered R0 by surgery. The median survival of all patients was 14.5 months (interquartile range, 6-30 months), and that of patients rendered R0 was 23 months (interquartile range, 10-37 months), in comparison with 7 months (interquartile range, 3-25 months) for those of R1 status (P =.006; log-rank method). Ability to achieve R0 status by synchronous or staged resection was the only factor predictive of survival. CONCLUSIONS: The presence of M1 disease per se should not preclude resection of local recurrence, although case selection is problematic.

Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers.

BACKGROUND AND AIMS: To evaluate the clinical outcome of selected patients with distal rectal cancer treated by preoperative radiation with or without chemotherapy and full-thickness local excision (FTLE). PATIENTS AND METHODS: Ten patients with invasive distal rectal cancer (six T2, four T3) were treated with preoperative radiotherapy (3600-5040 cGy) with or without 5-fluorouracil based chemotherapy. FTLE was performed 4-6 weeks after completion of radiotherapy, primarily because of comorbid diseases or patient refusal of a permanent colostomy. Median follow-up was 28.5 months. RESULTS: There were no prolonged wound complications, and only one positive microscopic margin was detected. Among three cases of complete pathological response, two remain without evidence of disease. All patients retained sphincter function and avoided creation of a stoma. Two patients developed recurrence, one with widespread disease including pelvic recurrence 26 months after surgery and the other with distant disease only at 23 months. There were four deaths: two unrelated to cancer, one of undetermined cause after 7 years, and one after widespread recurrence at 26 months, with death 4 months later. Two-year actuarial survival was 78%. CONCLUSIONS: This pilot study demonstrates that preoperative radiotherapy and FTLE avoids major abdominal surgery yet facilitates sphincter preservation, excision with negative margins, and short-term local control in selected patients with distal rectal cancer.

Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer.

Recently, an inducible microsomal human prostaglandin E synthase (mPGES) was identified. This enzyme converts the cyclooxygenase (COX) product prostaglandin (PG) H(2) to PGE(2), an eicosanoid that has been linked to carcinogenesis. Increased amounts of PGE(2) have been observed in many tumor types including colorectal adenomas and cancers. To further elucidate the mechanism responsible for increased levels of PGE(2) in colorectal tumors, we determined the amounts of mPGES and COX-2 in 18 paired samples (tumor and adjacent normal) of colorectal cancer. With immunoblot analysis, mPGES was overexpressed in 83% of colorectal cancers. COX-2 was also commonly up-regulated in these tumors; marked differences in the extent of up-regulation of mPGES and COX-2 were observed in individual tumors. Immunohistochemistry revealed increased mPGES immunoreactivity in neoplastic cells in both colorectal adenomas and cancers compared with adjacent normal colonic epithelium. Cell culture was used to investigate the regulation of mPGES and COX-2. Chenodeoxycholate markedly induced COX-2 but not mPGES in colorectal cancer cells. Tumor necrosis factor-alpha induced both mPGES and COX-2, but the time course and magnitude of induction differed. As reported previously for COX-2, overexpressing Ras caused a several-fold increase in mPGES promoter activity. Taken together, our results suggest that overexpression of mPGES in addition to COX-2 contributes to increased amounts of PGE(2) in colorectal adenomas and cancer. The mechanisms controlling the expression of these two enzymes are not identical.

Abdominoperineal resection for rectal cancer at a specialty center.

PURPOSE: Although sphincter-preservation procedures have replaced abdominoperineal resection as the treatment of choice for rectal cancer, a subset of patients with rectal cancer will still require abdominoperineal resection. The use of adjuvant radiotherapy has been shown to reduce local recurrence, and combined modality therapy (chemoradiation) improves survival. Sharp mesorectal excision compared with the classic teaching of blunt retrorectal dissection is also an important component of local control. The primary aim of the present study was to evaluate the postoperative complications associated with neoadjuvant therapy in patients requiring complete rectal excision. Oncologic outcomes for all patients with abdominoperineal resection are also provided. METHODS: A prospective database of 5,634 patients who underwent surgery for colorectal cancer at Memorial Sloan-Kettering Cancer Center between the years 1987 and 1997 was reviewed. Patients with primary adenocarcinoma of the rectum who underwent abdominoperineal resection were identified. In 1,622 patients who were operated on for primary rectal cancer, 292 patients (18 percent) underwent abdominoperineal resection and the rest had a sphincter-preserving procedure. Ten patients were excluded from the study because of prior pelvic irradiation for other cancer (8 patients) and insufficient radiation dose (<4,000 cGy; 2 patients). Neoadjuvant radiotherapy was given to 123 patients and postoperative adjuvant radiotherapy to 65 patients, whereas 94 did not receive radiotherapy. Intraoperative radiotherapy combined with preoperative radiotherapy was administered to 23 of the 123 patients given neoadjuvant radiotherapy. RESULTS: The duration of the operation was significantly longer in both neoadjuvant radiotherapy and intraoperative radiotherapy groups compared with the nonradiotherapy group (P = 0.01 and P < 0.0001, respectively). Estimated blood loss, mean number of blood units transfused per patient, and the percentage of patients being transfused were similar among the groups. Early postoperative complications were significantly higher in the neoadjuvant radiotherapy groups compared with the nonradiotherapy group. Late complications, overall survival, disease-free survival, and local recurrence were not significantly different among the groups. CONCLUSIONS: In patients with cancer of the lower one-third of the rectum, sharp pelvic dissection can result in a low rate of local recurrence even without radiotherapy. The role of preoperative radiotherapy, although associated with higher perineal wound complications, is important in increasing resectability and sphincter-preservation rate. Randomized, prospective trials will be needed to establish the role of adjuvant radiotherapy in patients undergoing sharp mesorectal excision for rectal cancer.

Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer.

BACKGROUND: Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome. METHODS: Patients having surgical debulking and IP 5-fluoro-2'-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively. RESULTS: There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m2 daily for 3 days) and IP leucovorin (240 mg/m2) with a median cycle number of 4 (range, 1-28). The median number of complications was 1 (range, 0-5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0-132 months). The median survival was 34 months (range, 2-132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection. CONCLUSIONS: Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator.

High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer.

PURPOSE: Management of locally recurrent colorectal adenocarcinoma represents a significant challenge. Many of these tumors adhere to or invade into vital pelvic structures rendering surgery or external beam radiotherapy (EBRT) as palliative treatment. Therefore, a treatment approach was developed to evaluate the role of high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component of therapy in the management of locally recurrent colorectal cancer. This is an update of our preliminary report with longer follow-up and larger patient numbers. METHODS AND MATERIALS: Between January 1992 and September 1998, 74 patients with locally recurrent rectal cancer were treated with surgery and HDR-IORT. Additional EBRT was given to 29 patients, and 33 patients received 5-fluorouracil based chemotherapy. All patients underwent complete gross resection, and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10 to 18 Gy. RESULTS: With a median follow-up of 22 months, the 5-year local control, distant metastasis disease-free, disease-free, and overall survival rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved local control was a negative margin of resection with a 5-year local control rate of 43%, compared to 26% in those with positive margin (p = 0.02). For overall survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p = 0.04) were significant predictors of improved survival. The incidence of peripheral neuropathy was 16%. CONCLUSION: The results with HDR-IORT in this group of patients are encouraging. Further improvements in local and distant control are still needed.

CEA is the major PHA-L-reactive glycoprotein in colon carcinoma cell lines and tumors: relationship between K-ras activation and beta1-6 branching of N-linked carbohydrate on CEA.

Previously we have shown that a positive correlation existed between the presence of beta1-6 branching of N-linked carbohydrate (detected as PHA-L reactivity) and the level of Ras activation in colon carcinoma cell lines. In these cell lines the major PHA-L-reactive species was found to be 180 kDa. Here we identified this species to be carcinoembryonic antigen (CEA) by demonstrating that: (a) CEA immunoreactivity and PHA-L reactivity colocalized on blots of crude cellular membranes from these cell lines, and that (b) immunoprecipitation of CEA resulted in quantitative coprecipitation of PHA-L reactivity at 180 kDa. Metabolic labeling of cell line HTB39 with [(3)H]mannose revealed that CEA was the predominantly labeled glycoprotein. This indicated that CEA was the major PHA-L-reactive species due its high level of expression. The amount of PHA-L reactivity present on CEA, expressed as the PHA-L/CEA ratio, was found to vary between cell lines. This ratio was found to correlate closely with the level of Ras activation in these cells. In cellular membrane isolated from primary colon carcinoma, the major PHA-L-reactive species was also 180 kDa. This reactivity colocalized with CEA immunoreactivity, indicating that the major beta1-6-branching glycoprotein in membranes from primary colon carcinoma was CEA. Similar to that seen in cell lines, the amount of PHA-L reactivity on CEA in human tumor samples varied, suggesting that a similar paradigm of Ras-induced expression of beta1-6 branching may occur in human colon carcinoma.

Pancreatic or duodenal resection or both for advanced carcinoma of the right colon: is it justified?

PURPOSE: The role of extended resections for locally advanced carcinomas of the right colon infiltrating duodenum and pancreas remains unclear. This investigation was undertaken to review our experience with pancreatic head or duodenal resections for advanced right-sided colon cancer. METHODS: The clinical, pathologic, and follow-up details of eight patients with bulky primary carcinomas of the right colon infiltrating the duodenum (n = 4) or pancreatic head (n = 4) surgically managed at Memorial Sloan-Kettering Cancer Center between 1986 and 1998 were reviewed. RESULTS: Six patients presented with anemia, and one patient each with epigastric pain and an abdominal mass. All patients had T4 lesions, whereas five had lymph node metastases at presentation. All patients were resected with clear pathologic margins either by right colectomy and en bloc duodenectomy (n = 4), or en bloc pancreaticoduodenectomy (n = 4). The 30-day mortality rate was zero. Six patients remained alive and free of disease at a median follow-up of 26 months, and there was one long-term survivor who was alive and free of disease at 84 months after resection. CONCLUSION: Extended resection for localized primary colonic carcinoma invading pancreas or duodenum can be undertaken safely and is associated with prolonged survival time.

Abdominal wall recurrence after colorectal resection for cancer.

PURPOSE: Disease recurrence in the abdominal wall from a primary colorectal cancer is a poorly studied and little understood phenomenon that has received renewed attention after the recognition of port site metastases in patients after laparoscopic colorectal resections. The purpose of the present study was to define the clinical, pathologic, and management issues in patients with abdominal wall metastases from colorectal cancer. METHODS: Patients presenting to Memorial Sloan-Kettering Cancer Center with a diagnosis of colorectal cancer were entered into a prospective database beginning in 1986. Review of this database showed that 31 patients presenting with recurrent disease in the abdominal wall were managed surgically at the institution between 1986 and 1998. RESULTS: A total of 31 patients (19 males) with a median age of 67 (range, 45-86) years presented with recurrent disease between 7 and 183 (median, 24) months after primary surgery. Primary tumors were located in the right colon in 17 patients, left colon in 2 patients, sigmoid colon in 7 patients, and rectum in 3 patients. Nineteen percent of primary tumors were perforated, 45 percent were poorly differentiated, 92 percent were transmural (T3 or T4), and 51 percent had lymph node metastases at presentation. Twenty-two patients presented with a symptomatic abdominal wall mass, whereas recurrence in the abdominal wall was found incidentally in 9 patients undergoing laparotomy. Four patients had isolated abdominal wall disease, whereas the remaining 27 were found to have associated intra-abdominal disease. Six patients who were left with residual intra-abdominal cancer after abdominal wall resection had a median survival time of four months. Twenty-five patients underwent a histologically complete resection of recurrence restricted to the abdominal wall alone (n = 4; median survival time, 18 months), abdominal wall and in continuity resection of adherent viscera (n = 15; median survival time, 12.5 months), or resection of abdominal wall and intra-abdominal recurrence at a distant site (n = 6; median survival time, 22 months, although only 1 patient remained alive with disease). The actual two-year and five-year disease-free survival rates were 16 and 3 percent, respectively. CONCLUSION: Abdominal wall metastases are often indicators of recurrent intra-abdominal cancer; however, aggressive resection in patients with disease restricted to the abdominal wall and associated adherent viscera can result in local disease control with little morbidity and no mortality.