Heidi Nelson

Early results of laparoscopic surgery for colorectal cancer - Retrospective analysis of 372 patients treated by clinical outcomes of Surgical Therapy (Cost) Study Group

PURPOSE: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, −4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.

Accuracy of computed tomography in determining resectability for locally advanced primary or recurrent colorectal cancers.

AIMnTo determine the accuracy of computed axial tomography (CT) in determining tumor resectability in patients with locally advanced primary (T4) or locally recurrent colorectal cancer.nnnMETHODSnComputed tomography scans of 84 patients with resectable locally advanced primary rectal cancer (n = 12) or recurrent colorectal cancer (n = 72) were compared with the operative findings to assess the accuracy of abdominal and pelvic CT in determining extent of disease and resectability.nnnRESULTSnAt surgery, disease was confined to the pelvis in 63 patients, the abdomen in 7, and involved both the pelvis and abdomen in 14. Computed tomography correctly identified these anatomic sites of tumor in 87% of patients, with 89% and 80% accuracies for pelvic and abdominal disease, respectively. Tumor resection was performed in 71 patients (85%), but was not in 13 patients because of locally unresectable disease in 8 and metastatic disease in 5. The accuracy of predicting tumor-related operability was 85%. With regard to adjacent organ resection, CT was accurate in determining the need for sacrectomy or hysterectomy, but overestimated the need for urinary organ resection. Based on histological examination of resection margins, CT correctly staged (n = 45) or overstaged (n = 9) 54 patients (64%) and understaged the remaining 30. The ability of CT to preoperatively predict a locally advanced tumor after preoperative radiation therapy as not being fixed was 30%, fixed but resectable 75%, and fixed but not resectable 25%.nnnCONCLUSIONSnComputed tomography is generally reliable at identifying disease as being confined to one region, and for predicting the need for adjacent organ resection. It is less discriminating for predicting local tumor resectability.

Are we overtreating rectal cancer: Time for another trial?

Routine use of adjuvant or neoadjuvant chemoradiation for all stage II and III rectal adenocarcinomas likely represents overtreatment. Radiation therapy for high-risk rectal cancer to reduce rates of local recurrence and cancer-related deaths has become standard. That radiation therapy is associated with both short-term and longterm morbidity and posttreatment dysfunctions supports the avoidance of such morbidities when the benefits are marginal. Increasing evidence, however, indicates that it is possible to be more selective in the application of radiation therapy, especially for T1–2N1 and T3N0 tumors. We propose that it is critical to treat, but equally important not to overtreat, patients with rectal cancer. Although surgery remains the primary curative modality in the treatment of rectal cancer, its limitation as a single curative modality has long been recognized. Historically, local recurrence rates after proctectomy for rectal cancer have been high, which prompted trials investigating the impact of adjuvant chemotherapy and radiation therapy (e.g., the Mayo/North Central Cancer Treatment Group [NCCTG] 7947511 and Gastrointestinal Tumor Study Group [GITSG] 7175.2) With time, it became clear that postoperative radiation and chemotherapy significantly reduced local recurrence and improved survival rates when compared with surgery alone, leading to the National Institutes of Health (NIH) consensus conference statement in 1990.3 This consensus conference concluded that all patients with tumor, node, metastasis (TNM) stage II and III rectal cancer should be treated with postoperative radiotherapy and chemotherapy. Perhaps, as a result of these breakthrough improvements in cancer outcomes, considerable clinical research activity has ensued in this field during the last 13 years. Accordingly, it seems prudent to review and reconsider these consensus recommendations in light of current knowledge. For example, surgery in the previous adjuvant trials was not standardized and local recurrence rates with surgery alone were high. Furthermore, patients selected for these trials represented a somewhat biased population, with only select patients with stage II and stage III cancer (those at high risk for local and distant recurrence) considered for enrollment. We now know that the surgeon is an important prognostic variable and that patients with stage II and stage III cancer have variable risk according to both “T” and “N” classification. It is time to determine if new practice guidelines are warranted, taking into the equation improvements in surgery and risk classification. The critical contribution of proper oncologic surgery to outcomes in rectal cancer has recently come to the forefront with the focus principally on mesorectal excision, radial margins, and lymphadenectomy. Although no prospective, randomized trial has compared total mesorectal excision (TME) with conventional proctectomy, both single institution series and at least one multicenter trial have demonstrated excellent local control rates with surgery alone. The Dutch TME study4 reported that, with appropriate training, the TME technique could achieve local recurrence rates as low as 8.2% with surgery alone, which is consistent with rates of 4% to 8%5,6 from single institution reports. Just as adequate clearance of the distal bowel margin helps prevent anastomotic recurrences,7 it is now known that clearance of the radial margin is critical for the prevention recurrences of pelvic cancers. Unlike the bowel margin, the radial margin can be involved despite proper wide oncologic resection (i.e., in the setting of a large bulky advanced pelvic tumor). A positive radial margin is associated with high recurrence rates of 66% to 85%8,9; the margin can be involved from inadequate surgical clearance or from an extensive, deeply penetrating tumor in the setting of widest possible surgical clearance. Finally, increasing emphasis is being placed on the adequacy of lymph node harvest. When a Received November 4, 2003; accepted November 24, 2003. From the Division of Colon and Rectal Surgery, Rochester, Minnesota. Address correspondence to: Heidi Nelson, MD, Division of Colon and Rectal Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905; Fax: 507-284-1794; E-mail: nelson.heidi@mayo.edu.

Anti-tumor × anti-CD3 heteroconjugates direct human peripheral blood lymphocytes to lyse colon tumor cells

T lymphocytes normally recognize antigens through the antigen receptor complex (TCR/CD3) but can be redirected to bind and lyse unrecognized tumor cells by anti-tumor X anti-CD3 heteroconjugates. Chemical coupling of an antibody directed against the T cell receptor complex and an antibody directed against tumor antigen produces a conjugated antibody that activates the T cell lytic mechanism and bridges the T cell and tumor cell. We tested the lytic activity of heteroconjugate-treated cultured human peripheral blood lymphocytes (PBLs) in 4-h radioactive chromium release assays with human colon tumor cell targets. PBLs were enriched for T cells by the depletion of Leu11a+ and Leu19+ cells, prior to culture in rIL-2 and anti-CD3. Cultured human PBLs depleted of Leu11a+ and Leu19+ cells produced low levels of tumor cell lysis in the absence of antibodies. Anti-tumor X anti-CD3 heteroconjugates significantly enhanced tumor cell lysis by cultured PBLs when tested against four different colon tumor cell lines (P less than 0.005), but, heteroconjugates in the absence of PBLs did not augment tumor cell lysis. Cultured PBLs treated with monoclonal anti-tumor antibody, with monoclonal anti-CD3 antibody, or with irrelevant heteroconjugate did not enhance tumor cell lysis. We conclude that heteroconjugate-directed lysis is mediated by PBLs and that both the anti-tumor antibody and the anti-CD3 antibody are essential for heteroconjugate function. In addition, heteroconjugate-enhanced tumor cell lysis is mediated through a mechanism other than antibody-dependent cellular cytotoxicity or nonspecific T cell receptor crosslinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Current status of laparoscopic colectomy—Is it experimental?

The introduction of laparoscopic cholecystectomy ushered in dramatic changes in the approach to abdominal surgery. The ability to remove abdominal organs through small incisions, thereby reducing pain and time for recovery, rapidly became popular among patients and effectively revolutionized the approach to cholecystectomy. Its continued popularity encourages applications of laparoscopic surgery in other fields. Developments in the field oflaparoscopic colon and rectal procedures have paralleled those of laparoscopic cholecystectomy, the latter of which has proceeded at a more control led pace and with more prospective assessments. T h e introduction and acceptance of laparoscopic colectomy was more gradual for a number of reasons including the fact that it is technically challenging, has less dramatic patient benefits, and perhaps most significantly may represent a compromise as an oncologic procedure. Early clinical series with cancer patients are encouraging as they show that, with proper technique, adequate margins and lymph node harvests can be achieved. Studies based on animal models, however, have indicated that patients may incur a risk as well when laparoscopy is used in the treatment of colon cancer. Some studies have shown a promotion of tumor growth and dissemination with CO2 pneumoperi toneum, whereas other researchers see no impact of laparoscopy on tumor growth and even propose an oncologic benefit f rom the documented preservation of the host immune response with the less invasive laparoscopic surgery. Today most researchers agree that the phenomenon of port-site implantat ion is mostly related to the well-described wound trophic effects or to poor surgical technique-problems that are not unique to laparoscopic cancer surgery. Wha t has been learned about laparoscopic colectomy so far is that it is feasible--that is, it can be performed with acceptable operative times and conversion rates. To learn the technique and achieve proficiency requires between 20 and 100 cases for most surgeons. As the next generation of laparoscopically facile surgeons emerges from residency and fellowship training, the learning curve has become considerably lower than that experienced by the previous generation. Most trainees can now be taught a segmental colectomy within 10 to, at most, 15 cases. Forinnately safety, as measured by morbidity and mortality, has not been a serious problem in previous series. These studies found at least equivalent rates of complications to the open procedure even during the learning phase. Those practicing laparoscopic colectomy continue to be encouraged about its furore, as it is clear that patient-related benefits can be realized. Patients typically recover more quickly with reduced requirements for narcotics, reduction in length of ileus, and a shorter hospital stay, 2 to 4 days on average. Finally, it must be admitted that when the benefits were not initially compelling and the oncologic resuits were reason for concern, a general slowdown was encouraged. The controlled introduction of laparoscopic colectomy has allowed better definition of patient-related benefits, and as well has allowed for a critical assessment of cancer risks. Thus, although it is established that laparoscopic colectomy is feasible, safe, and associated with patient-related advantages, the oncologic risks are not yet established. A formal risk/benefit analysis can only be forthcoming at the close of ongoing national and international prospective studies. Early results of at least three of these randomized prospective trials show equivalent results in recovery, margins, complication rates, and local/ regional recurrences. There are, to date, no reports describing the impact of the laparoscopic approach on longterm survival. Because of this, at least for now, the answer to the question Is it experimental? must be no for benign condit ions but yes for cancers.

Laparoscopic resection of inflammatory bowel disease

PURPOSE: To determine the feasibility of laparoscopic resection of inflammatory bowel disease. METHODS: A retrospective chart review was performed of laparoscopic procedures for Crohns disease (CD) or chronic ulcerative colitis (CUC). RESULTS: One hundred and forty four patients were reviewed, 89 females and 55 males, age 15 to 78 years (mean 38 years). The most common diagnosis was CD, in 128 patients, with CUC in 15 and indeterminate colitis in 1 patient. Of patients with CD, 58 (40%) had previous abdominal operations, 32 for prior resection of CD and 26 unrelated to CD. The indication for operation in CD was refractory disease in 27, and obstruction +/stricture in 39 patients; 49 patients had a preoperative diagnosis of fistula, phlegmon or abscess. There were unexpected intraoperative findings in 41 patients, with phlegmon and fistula being the most common intraoperative findings. The conversion rate for patients with CD was 20/128 or 15.6%, and 2/15 or 13% in CUC. Among the 27 patients in whom the preoperative indication was solely refractory disease, only 4 had unexpected intraoperative findings, and there were no conversions. Among those patients who had a preoperative diagnosis of obstruction +/stricture, 9 had unexpected findings at laparoscopy, and the conversion rate was 4/39 or 10%. Of those 49 patients with a preoperative diagnosis of fistula, abscess or phlegmon, the conversion rate was 14/49 or 29%, and 23 of these patients had additional unexpected findings at laparoscopy. Overall there were 8 intraoperative complications, for a rate of 5.6%. The post-operative complication rate was 17/144 or 12%; of these, 4 were wound infections, for a rate of 4/144 or 2.7%. There was no operative mortality. The mean length of stay for the whole series, including converted cases, was 5.7 days. CONCLUSIONS: The laparoscopic approach is highly feasible in CUC and in CD, with low conversion rates in the absence of preoperative findings of fistula, abscess or phlegmon. Even with a preoperative diagnosis of fistula, abscess or phlegmon, the laparoscopic approach is feasible in 70% of patients.