Richard L. Whelan

Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES).

BackgroundThe European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002.MethodsA systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer.ResultsAdvanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery.ConclusionLaparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.

Intestinal tuberculosis: return of an old disease

Objective:Tuberculosis (TB) can no longer be considered a rare disease in the United States due, in part, to the AIDS epidemic. Because the signs and symptoms of intestinal TB are nonspecific, a high index of suspicion must be maintained to ensure a timely diagnosis. The aim of this article is to review the history, epidemiology, pathophysiology, and treatment of TB.Methods:This review is based on an examination of the world literature.Results:In only 20% of TB patients is there associated active pulmonary TB. Areas most commonly affected are the jejunoileum and ileocecum, which comprise >75% of gastrointestinal TB sites. Diagnosis requires colonoscopy with multiple biopsies at the ulcer margins and tissue sent for routine histology, smear, and culture. If intestinal TB is suspected, empiric treatment is warranted despite negative histology, smear, and culture results. Treatment is medical, and all patients should receive a full course of antituberculous chemotherapy. Exploratory laparotomy is necessary if the diagnosis is in doubt, in cases in which there is concern about a neoplasm, or for complications that include perforation, obstruction, hemorrhage, or fistulization.Conclusions:This review draws attention to the resurgence of tuberculosis in the United States. An increased awareness of intestinal tuberculosis, coupled with knowledge of the pathophysiology, diagnostic methods, and treatment should increase the number of cases diagnosed, thus improving the outcome for patients with this disease.

Postoperative immune function varies inversely with the degree of surgical trauma in a murine model.

AbstractBackground: Major surgery through a laparotomy incision is associated with a postoperative reduction in immune function. Studies in rats involving sham procedures suggest that immune function may be preserved after laparoscopy. This study investigates the effects of incision length and exposure method for bowel resection with respect to postoperative immune function as assessed by delayed-type hypersensitivity (DTH) reactions. Methods: Male Sprague Dawley rats (n= 175) were challenged preoperatively, immediately postoperatively, and on postoperative day 2 with an intradermal injection of 0.2 mg phytohemagglutinin (PHA), a nonspecific T-cell mitogen. The averages of two measures of perpendicular diameters were used to calculate the area of induration. Anesthesia control rats underwent no procedure. Minilaparotomy rats underwent a 3.5-cm midline incision. Sham full laparotomy rats underwent a 7-cm midline incision. The open bowel-resection group underwent a cecal ligation and resection through a 7-cm midline incision. In the laparoscopic-assisted resection group a CO2 pneumoperitoneum and four-port technique was utilized to deliver the cecum through a 4-mm port where the cecum was extracorporeally ligated and resected. Results: Preoperative responses were similar in all five groups. Incision length: Full laparotomy group responses were 20% smaller than anesthesia control responses on postoperative day (POD)1 through POD4 (p < 0.02). At no time point were the responses in the minilaparotomy group significantly different from either anesthesia control or full laparotomy group responses. Exposure method: The laparoscopic-assisted resection group responses were 20% larger than open group responses at the time of two of the four postoperative measurements (p < 0.05, both comparisons). At all postoperative time points, open resection group responses were significantly smaller than control responses (p < 0.05, all comparisons), whereas at no time point were laparoscopic group responses significantly different from control responses. Conclusion: We conclude that postoperative cell-mediated immune function varies inversely with the degree of surgical trauma. Results from the minilaparotomy and laparoscopy groups suggest that procedures done through small incisions may result in preservation of postoperative immune function.

Preservation of immune response after laparoscopy

We evaluated the immunologic responses following laparoscopic and open surgery by comparing delayed type hypersensitivity induration size before and after each method of accessing the abdominal cavity. One hundred and thirty-two male Sprague-Dawley rats were sensitized with keyhole limpet hemocyanine (KLH). Animals were challenged with KLH and phytohemaglutanin (PHA) 10 days after sensitization. On day 14 after initial sensitization animals were randomly divided into three groups. Group one served as controls and had no procedure performed, group two underwent peritoneal insufflation with carbon dioxide gas to a pressure of 6–8 mm Hg for one half hour, and rats in group three had a midline laparotomy which was closed after one half hour. Each rat was challenged with KLH immediately and at three days post-operatively. The area of induration in response to each of the challenges was measured with calipers 24 and 48 hours after the challenge. Results of this skin testing showed that the group of animals that underwent laparotomy, despite having normal responses preoperatively, had significantly diminished responses to both KLH and PHA when challenged postoperatively. The insufflated group showed no differences from control animals at any time point examined. We conclude that DTH response in this model is better preserved after laparoscopy than laparotomy.We further conclude that the defect in DTH response is in the effector arm. The question of the clinical significance of these findings is addressed.

Hand-Assisted Laparoscopic vs. Laparoscopic Colorectal Surgery: A Multicenter, Prospective, Randomized Trial

PurposeThis study was designed to compare short-term outcomes after hand-assisted laparoscopic vs. straight laparoscopic colorectal surgery.MethodsEleven surgeons at five centers participated in a prospective, randomized trial of patients undergoing elective laparoscopic sigmoid/left colectomy and total colectomy. The study was powered to detect a 30-minute reduction in operative time between hand-assisted laparoscopic and straight laparoscopic groups.ResultsThere were 47 hand-assisted patients (33 sigmoid/left colectomy, 14 total colectomy) and 48 straight laparoscopic patients (33 sigmoid/left colectomy, 15 total colectomy). There were no differences in the patient age, sex, body mass index, previous surgery, diagnosis, and procedures performed between the hand-assisted and straight laparoscopic groups. Resident participation in the procedures was similar for all groups. The mean operative time (in minutes) was significantly less in the hand-assisted laparoscopic group for both the sigmoid colectomy (175 ± 58 vs. 208 ± 55; P = 0.021) and total colectomy groups (time to colectomy completion, 127 ± 31 vs. 184 ± 72; P = 0.015). There were no apparent differences in the time to return of bowel function, tolerance of diet, length of stay, postoperative pain scores, or narcotic usage between the hand-assisted laparoscopic and straight laparoscopic groups. There was one (2 percent) conversion in the hand-assisted laparoscopic group and six (12.5 percent) in the straight laparoscopic group (P = 0.11). Complications were similar in both groups (hand-assisted, 21 percent vs. straight laparoscopic, 19 percent; P = 0.68).ConclusionsIn this prospective, randomized study, hand-assisted laparoscopic colorectal surgery resulted in significantly shorter operative times while maintaining similar clinical outcomes as straight laparoscopic techniques for patients undergoing left-sided colectomy and total abdominal colectomy.

Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans.

BACKGROUND Animal studies have documented significantly better preserved postoperative cell-mediated immune function, as measured by serial delayed-type hypersensitivity (DTH) challenges, after laparoscopic-assisted than after open bowel resection. Similarly, in humans, the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses; whereas after laparoscopic cholecystectomy, no significant change in DTH response has been noted. The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy. METHODS A total of 35 subjects underwent either laparoscopic (n = 18) or open colectomy (n = 17) in this prospective but not randomized study. Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study. DTH challenges were carried out at three time points in all patients: preoperatively, immediately following surgery, and on the third postoperative day (POD 3). Responses were measured 48 h after each challenge and the area of induration calculated. There were no significant differences between the laparoscopic (LC) and open (OC) colorectal resection groups in regard to demographics, indications for surgery, or type of resection carried out. The percentage of patients transfused was similar in both groups (17%, LC; 12% OC; p = NS). In the LC group, all cases were completed without conversion using minimally invasive methods. There were no perioperative deaths, and the rate of postoperative complications was similar in both groups. The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods. RESULTS In regards to the OC group results, the median sum-total DTH responses for the day of surgery challenges (0.44 +/- 69 cm2) and the POD 3 challenges (0.72 +/- 3.37 cm2) were significantly smaller than the preoperative results (3.61 +/- 3.83 cm2, p <0.0005 vs op day and p <0.0003 vs POD 3 results). When the LC group results were similarly analyzed, no significant difference in DTH response was noted between the pre- and the postoperative challenge results. Additionally, when the median percent change from baseline was calculated and considered for the OC groups DTH results, both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results (vs day of surgery, p <0.007; vs POD 3, p <0.006). Similar analysis of the LC groups results yielded nonsignificant differences between the pre- and postoperative responses. Lastly, when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges, a significant difference was noted for the POD 0 challenge (LC, -21%; OC 88%; p <0.004) but not for the POD 3 challenge. CONCLUSIONS The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses. This was not the case for the laparoscopic group (a combination of fully laparoscopic and laparoscopic-assisted resections). When the open and laparoscopic groups results are directly compared, regarding the results of the day of surgery DTH challenges, the LC groups median percent change from baseline was significantly less than that observed in the OC group. These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively, whereas in this study laparoscopic colorectal resection was not. Further human studies are needed to verify these findings and to determine the clinical significance, if any, of this temporary difference in immune function following colon resection.

Better preservation of immune function after laparoscopic-assisted vs . open bowel resection in a murine model

PURPOSE: We evaluated cell-mediated immune function after laparoscopic-assisted and open bowel resection in rats by measuring delayed-type hypersensitivity responses to keyhole limpet hemocyanin (KLH) and phytohemagglutinin (PHA). METHODS: Male Sprague-Dawley rats (n=120) were sensitized to 1 mg of KLH ten days before investigations. Rats were challenged preoperatively, immediately postoperatively, and on postoperative day (POD) 2 with an intradermal injection of 0.3 mg of KLH and 0.2 mg of PHA (at different sites). Averages of two measures of perpendicular diameters (taken 24 and 48 hours postchallenge) were used to calculate the area of induration using the formula for the area of an ellipse, A=(D1/2×D2/2)×π. Anesthesia control animals underwent no procedure (n=40). Open resection group underwent ligation and resection of the cecum (length=2 cm) through a 7 cm midline incision (n=40). In the laparoscopic-assisted resection group, under CO2 pneumoperitoneum (4–6 mmHg), the cecum was identified, dissected free, and exteriorized through a 4 mm port. The cecum was then ligated and resected extracorporeally (n=40). RESULTS: Preoperative responses to both KLH and PHA were the same in all three groups. Furthermore, within each group, postoperative responses were similar. When groups were compared, the anesthesia group responses were significantly greater than the open resection group responses at all time points (P<0.05 for all comparisons). Laparoscopic-assisted resection group responses differed from control at only two of eight postoperative measures. Laparoscopic resection group responses were significantly greater than open resection group responses to challenge with both KLH and PHA on POD1 (P<0.02, for both comparisons) and POD 4 (P<0.05, for both comparisons). CONCLUSIONS: Postoperative cell-mediated immune function is better preserved after laparoscopic-assisted bowel resection than after open resection as assessed by skin antigen testing.

Trocar site recurrence is unlikely to result from aerosolization of tumor cells.

PURPOSE: This study was undertaken to investigate the ability of a high-pressure CO2 environment to aerosolize tumor cells in bothin vitroandin vivo models. (An aerosol is defined as a stable gaseous suspension of insoluble particles.) Also, this study was designed to determine if rapid desufflation is capable of transporting fluid laden with tumor cells. METHODS: The fourin vitro aerosol experiments were performed in an 18.9-l plastic vessel fitted with two 7-mm ports and a compliant latex balloon affixed to the top. After CO2 insufflation, the vessel was desufflated through a sterile soluset containing 25 ml of culture media that was subsequently emptied into a culture dish, incubated for two weeks, and periodicallyassessed for growth. At the bottom of the vessel, one of the following was placed: Study 1 and 2, a suspension of B16 melanoma or colon 26 tumor cells in liquid culture media; Study 3, colon 26 cells in saline solution; Study 4, several pieces of solid colon 26 tumor. In Studies 1 to 3, cell preparations were subjected to the following high-pressure CO2 conditions (pneumo): 1) static pneumo of 15 and 30 mmHg (10 minute dwell); 2) a continuous flow (CF) of CO2 (10 l) while maintaining a pressure of 15 or 30 mmHg in the vessel. In Study 4, only the 30 mmHg static and CF conditions were tested. Between 6 and 12 determinations were performed for each condition and cell preparation.In vivo aerosol experiments consisted of Spraque Dawley rats that received intraperitoneal injections of 10-5 B16 cells in 0.1 ml of liquid media.Two laparoscopic ports were placed in the abdomen, one each for insufflation and desufflation. Study groups were: 1, static CO2 pneumo of 15 mmHg; 2 and 3, continuous CO2 flow (10 l) at a stable pneumo pressure of 5 and 10 mmHg. Desufflation was performedvia the same collecting device and handled in an identical manner to thein vitroexperiments described above. Thein vitro balloon experiment was designed to investigate the ability of desufflation to transport fluid-containing tumor cells; latex balloon model was used. To prevent complete loss of volume on desufflation, a wire coil was placed inside the balloon. Twenty ml of media containing 20×10−6B16 cells was placed in the bottom of the balloon. The balloon was insufflated with 1 to 21 of gas. There were three study groups that differed in the degree to which the cell suspension was agitated before desufflation. Study conditions were as follows: 1) no agitation; 2) moderate agitation to coat the lower walls and coil; 3) maximum agitation to coat the entire balloon. To verify the viability of tumor cells,at the end of eachin vitroandin vivo study, a sample of tumor cells or peritoneal washing was incubated in sterile media. These samples served as positive controls. RESULTS:In vitro aerosol studies consisted of the following. At the end of two weeks of incubation, no tumor growth was noted in any of the 124 test dishes. The 14 control samples all demonstrated tumor growth.In vivo aerosol studies consisted of the following. Zero of 18 experimental dishes grew tumor. All three peritoneal washing samples demonstrated growth.In vitro balloon studies consisted of the following. Zero of 12 test dishes in Groups 1 and 2 demonstrated growth, whereas five of six dishes did so in Group 3 (maximally agitated before desufflation). Again, positive controls all grew tumor cells. SUMMARY: We were unable to demonstrate aerosol formation in any of thein vitroandin vivo studies performed. In the balloon experiment, desufflation-related transport of tumor cells was demonstrated but only when the entire balloon surface was coated with the tumor cell suspension before desufflation. CONCLUSION: Aerosols of tumor cells are not likely to form. Free intraperitoneal tumor cells are most likely found in liquid suspension. Desufflation is a potential means of transport of cell-laden fluid.

Is immune function better preserved after laparoscopic versus open colon resection

The purpose of this preliminary study was to evaluate immunologic responses to laparoscopic vs standard open colon resection and to evaluate possible mediators of any differences found. Specifically, we compared cortisol levels and delayed-type hypersensitivity response after each method of colon resection in a group of 20 pigs.Two groups of 10 animals each were treated in identical fashion including bowel preparation, anesthesia, and postoperative management. The only difference between groups was that one underwent laparoscopic and the other an open colon resection. Blood specimens for cortisol were drawn before, during, and immediately postoperatively as well as at 11A.M. on postoperative days 1 and 2. All animals had been previously immunized as piglets with Sow Bac-E (Oxford Veterinary, Worthington, MN), an antigen preparation of common pig pathogens. At the conclusion of the operative procedure 0.5 cc of the antigen was injected intradermally on the right forelimb of the animals. At 48 and 72 h postoperatively the largest diameters of induration surrounding the injection site were measured and averaged. Cortisol levels were measured in serum samples by radioimmunoassay (Met-Path, Rockville, MD). Statistical significance was determined by t-test.Results of skin antigen testing showed that the group of pigs that underwent laparoscopic resection had a 20% greater response, 1.54 cm±0.28 cm at 48 h and 1.53 cm±0.18 cm at 72 h. For the open-surgery group results were 1.24 cm±0.26 cm at 48 h and 1.32 cm±0.21 cm at 72 h,P<0.05 for the difference between groups at both 48 and 72 h. Cortisol levels were not significantly different between groups at any of the time points.We conclude that T-cell-related immune function in this model, as measured by delayed-type hypersensitivity, is better preserved after laparoscopic than open colon resection. We further conclude that cortisol levels are not responsible for the improved preservation of the immune response. The benefits of improved postoperative immune function may be significant for patients undergoing laparoscopic colon resection.

Increased tumor establishment and growth after open vs laparoscopic surgery in mice may be related to differences in postoperative T-cell function

AbstractBackground: Previous work has demonstrated that cell-mediated immune function in rats is better preserved after laparoscopic than open surgery. We have also shown that tumors are more easily established in mice and grow larger after sham laparotomy than after pneumoperitoneum. The purpose of this study is to determine if the functional status of the cell-mediated immune system influences postoperative tumor growth. Methods: Immunocompetent (study 1) and T-cell deficient athymic (study 2) mice were injected with mouse mammary carcinoma cells in the dorsal skin. Mice then underwent either no procedure, midline laparotomy, or carbon dioxide pneumoperitoneum. Tumor masses on postoperative day 12 were compared. Results: In immunocompetent mice, laparotomy group tumors were nearly twice as large as laparoscopy group tumors (p < 0.02), which were 1.5 times as large as control group tumors (NS). In the athymic model, however, differences between the sham laparotomy and pneumoperitoneum groups were lost (p > 0.5). Tumors grew much larger in the athymic control mice than in the immunocompetent control mice (p < 0.01). Conclusion: We conclude that T-cell function plays a significant role in host containment of mouse mammary carcinoma and in the mechanism of differences in tumor growth observed after laparotomy and pneumoperitoneum.