Preoperative Hyperoxyradiotherapy of Colorectal Carcinoma

Aim: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. Patients and Methods: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplan-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A. four patients, B: 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was peformed extending from the perineum to the vertebral L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). Results: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6ndash;105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of approximately 61.5% and a local relapse-free survival rate of approximately 84.2% can be expected. Treatment failures were predominantly systemic. Conclusion: We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncancerous tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma. Zusammenfassung Zielsetzung: Analyse von frühen und späten Nebenwirkungen und Komplikationen bei präoperativer lokoregionärer akzelerierter Hypoxyradiotherapie kolorektaler Karzinome. Patienten und Methoden: Zwischen April 1991 und Februar 1997 wurden 50 Patienten (36 Männer und 14 Frauen) mit kolorektalen Karzinomen präoperativ durch lokoregionäre akzelerierte hypofraktionierte Hypoxieradiotherapie behandelt. Die Beurteilung des Erkrankungsausmaßes erfolgte nach Dukes-Kriterien (A: vier Patienten, B: 28 Patienten, C: 18 Patienten). Ein 20-MeV-Linearbeschleuniger mit zwei opponierenden Feldern auf zwei Ebenen wurde verwendet. Die akute Hypoxie wurde während der Bestrahlung durch Atmen eines hypoxischen Gasgemischs von 7,8-8,0% Sauerstoff induziert. Gesamtdosen von 24 Gy/8 tage, 28 Gy/9 Tage bzw. 32 Gy/10 Tage wurden bei fünf, 20 bzw. 25 Patienten verabreicht. Eine anteriore Resektion oder abdominoperineale Amputation des Rektums wurde 1 Tag nach Abschluss der präoperativen Hypoxieradiotherapie durchgeführt. Die Bewertung der frühen Reaktionen nach Bestrahlung erfolgte nach den "Common Toxicity Criteria of the National Cancer Institute" (CTC-NCI). Ergebnisse: Nach Irradiation wurden bei drei Patienten eine frühe Proktitis und bei zwei Patienten eine frühe bestrahlungsbedingte Zystitis festgestellt. Weder akute noch späte strahlenbedingte Komplikationen wurden beobachtet. Auf der Grundlage der Kaplan-Meier-Analyse (median 48 Monate) könne eine 5-Jahres-Gesamtüberlebensrate von ca. 61,5% und eine lokal rezidivfreie Überlebensrate von ca. 84,2% erwartet werden. Schlussfolgerung: Die akute Hypoxie übt während akzelerierter Hypoxieradiotherapie kolorektaler Karzinome eine radioprotektive Wirkung auf Normalgewebe aus. Die Hypoxieradiotherapie erlaubt eine sichere Verabreichung von Dosen, die die Toleranzgrenze von gesunden Organen überschreiten.     

Adjuvant radiotherapy and anastomosis in rectal cancer—disturbing evidence from animal studies

PURPOSE: Adjuvant radiotherapy is used increasingly in the management of rectal cancer. However, ionizing radiation is mutagenic, and, superimposed on a background of increased cellular proliferation as seen around anastomoses and in colorectal cancer patients, there is the potential for enhanced metachronous cancer risk. METHOD: The influence of preoperative irradiation on both carcinogenesis and cellular proliferation at colonic anastomoses was explored in 180 adult male F344 rats. Orthovoltage x-rays were delivered to the distal descending colon by parallel opposed fields. Ninety rats received 16 Gy in one fraction; the remainder received 36 Gy in two fractions one week apart. In each irradiation group 18 rats either acted as controls or one week after radiotherapy underwent distal colotomy and repair. RESULTS: We found the descending colon susceptible to radiation carcinogenesis; 26 colorectal tumors developed in the low-dose irradiation group and 47 in the highdose group (P=0.0008; Mann-Whitney U test, 16 vs. 36 Gy). Preferential tumor development was seen in the anastomotic region. In those animals that underwent surgery and irradiation, among the low-dose irradiation group only 3 of 72 had tumors within the descending colon compared with 21 of 72 at the anastomotic site (McNemar's test chi-squared=40.9; P<0.001), and in the high-dose irradiation group 5 of 72 had tumors within the descending colon compared with 36 of 72 at the anastomotic site (McNemar's test chi-squared=22.0; P<0.001). Anastomotic crypt cell production rates were increased for at least three months following exposure to irradiation (16 Gy: f=15.1,P<0.005; 32 Gy: f=9.4,P<0.005). CONCLUSIONS: Radiation carcinogenesis is greatly enhanced at colonic anastomoses and may result from altered anastomotic proliferation. This has potentially disturbing implications in view of the increasing use of adjuvant radiotherapy for rectal carcinoma.     

Prevalence of Serum p53 Antibodies against Tumor p53 Protein in Colorectal Cancer

Background: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Egyptian subjects. The aim of this study was to investigate tissue p53 overexpression in paraffin embedded tumor and serum p53 antibodies in colorectal cancer patients with special reference to patient outcome.Patients and Methods: The study was conducted to 135 consecutive colorectal cancer patients. The tumor p53 protein was overexpressed in 60% and serum p53 antibodies in 35%, also tumor p53 accumulation is not necessarily associated with serum p53 antibodies positive cases. Tumor p53 overexpression was more frequent in distal colorectum than in proximal tumor (63.7% vs 41%) (p > 0.05).Results: Both tumor p53 overexpression and serum p53 antibodies increased signficantly with the stage of the tumor and lymph node involvement, but not with the grade, histopathological types and other histologic parameters. After a follow-up of 5 years, in the Kaplan Meier univariate analysis the factors stage (p = 0.0004), tumor p53 immunostaining (p < 0.0001) and serum p53 antibodies (p < 0.04) had a prognostic value.Conclusion: In conclusion p53 overexpression was associated with advanced histopathological stage and a high risk of recurrence.     

Improved local control and survival with the “sandwich” technique of pelvic radiotherapy for resectable rectal cancer

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy groupvs.7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P=0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P=0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.     

Hospital-Acquired Pneumonia in Critically Ill Patients

Study objectives: To identify, in patients experiencing hospital-acquired pneumonia (HAP), prognostic factors present at disease onset and build an algorithm capable of stratifying mortality risk upon HAP onset. Design: Observational cohort from January 1994 to December 2001. Setting: One intensive care unit (ICU) from a university-affiliated, urban teaching hospital. Patients: All consecutive patients exhibiting bacteriologically documented HAP either on ICU admission or during ICU stay. Interventions: Data collection and multivariate analysis using Chi-Square Automatic Interaction and Detection technique. Results: 168 patients were studied. The overall mean mortality rate was 49.4%. Upon onset of HAP, five independent variables allowed binary stratification of mortality risk. These consisted of underlying diseases (nonfatal versus ultimately and rapidly fatal diseases), Simplified Acute Physiology Score II (less than versus ≥37), platelet count (less than versus ≥150 000/mm³), chest x-ray involvement (1 versus >1 lobe), and PaO₂/FiO₂ (less than versus ≥167mm Hg). A branching algorithm consisting of these five variables identified patients with HAP at both low (<35%) and high (>75%) risk of mortality. Conclusion: Mortality in ICU patients with HAP may be predicted early, upon onset of HAP, by the cumulative use of prognostic factors in an algorithm.     

Präoperative Kurzzeitbestrahlung beim tief sitzenden Rektumkarzinom

Background: Although some trials have shown a lower rate of local recurrences after preoperative irradiation rectal carcinoma, the indication for preoperative irradiation in resectable low rectal cancer, is discussed controversely. Patients and Methods: In this study a differentiated concept is demonstrated: patients with uT2-tumor received no preoperative adjuvant therapy, whereas patients with uT3-carcinoma received preoperative short-time irradiation with 25 Gy on 5 days. We present the results of 85 patients who underwent total mesorectal excision and colonic J-pouch-anal anastomosis between 01.07.1999 and 30.06.2001. Forty-seven patients with uT2-cancer underwent surgery alone and 38 had preoperative short-time irradiation. Primary stoma was constructed in 42 patients (surgery alone: 18 [39%], preoperative irradiation: 24 [63%]). In the surgery alone group two patients underwent relaparotomy and secondary stoma construction due to anastomotic dehiscence. Three female patients needed secondary stoma for rectovaginal fistulas. In the irradiation group two female patients received secondary stoma construction for rectovaginal fistulas. The overall rate of anastomotic complications with required reoperation was 9.9%. It was not higher in the patients with preoperative irradiation than in the surgery alone group. Results: The early functional results were slightly worse after preoperative irradiation. In follow-up only one anastomotic recurrence occurred in a patient without preoperative irradiation. Another patient developed a pT1-carcinoma in the pouch, which could be treated by transanal excision. Conclusion: From our point of view preoperative short-time irradiation is a good supplement in the therapy of uT3-tumors of the lower rectum. We did not observe negative influences on anastomotic healing or functional results. Because of the short follow-up time with a median of 23 months definitive statements concerning the rate of local recurrences have to be evaluated by former studies.     

Colorectal carcinogenesis

PURPOSE: In view of the changing concept of colorectal carcinogenesis during the last 20 years, a historical review of colorectal carcinogenesis is presented. METHODS: The changing concept of colorectal carcinogenesis was presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neoplasms; 4) carcinogenesis based on molecular biology. RESULTS: In the first period, large adenomas were thought to play the most important role as precursors to colorectal carcinomas; however, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on the new precursor of colorectal carcinomas that were not recognized in the past. Molecular biology clarified a lack of K -ras mutation in nonpolypoid, particularly depressed, neoplasms, suggesting the presence of a novel pathway of colorectal carcinogenesis, different from that in polypoid neoplasms. CONCLUSIONS: The concept referred to as the “adenoma-carcinoma sequence” changed because colonoscopic polypectomy specimens were studied, and rather small, nonpedunculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolypoid neoplasms provides us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms, and genetic alterations in so-called de novo carcinomas need to be clarified     

Interleukin-6 and stress hormone responses after uncomplicated gasless laparoscopic-assisted and open sigmoid colectomy

PURPOSE: Laparoscopic colectomy has increasingly been advocated as an option for treatment of colonic disease. The purpose of this study was to compare effects of laparoscopicassisted sigmoid colectomy (LAS) and conventional open colectomy (OPEN) on postoperative cytokine and stress hormone responses. METHODS: Fourteen patients with sigmoid colon cancer, apparently free of preoperative complications, were analyzed. Patients in both groups underwent sigmoid colectomy with lymphadenectomy. LAS was performed by the gasless abdominal wall-lifting method. A 5 cm incision was placed at the beginning of the operation. Blood samples were taken preoperatively and postoperatively for measurement of interleukin-6, glucagon and C-reactive protein. Urinary catecholamine excretions were also determined postoperatively. RESULTS: The two groups of patients were similar with respect to age (61±7 for LASvs.64±9 for OPEN) and sex. Intraoperative blood loss did not differ significantly between groups (112±97 ml for LASvs.366±380 ml for OPEN). Operative times for LAS tended to be longer than those for OPEN (231±67vs.169±45 minutes;P=0.08). Similar time courses of postoperative interleukin-6, C-reactive protein, and stress hormone responses were observed in both groups. No significant differences were observed in the magnitude of changes except that the serum interleukin-6 level on day of surgery (postoperative day 0) was significantly higher in LAS patients than in those receiving OPEN. In addition, interleukin-6 levels showed a significant positive correlation with operative duration (r=0.582;P<0.05). CONCLUSIONS: Data suggest that stress responses after sigmoid colectomy, in patients undergoing LAS, are comparable with those of patients receiving OPEN and that the early interleukin-6 response after surgery appears to be associated with operative time.     

Die Wertigkeit der Positronenemissionstomographie (PET) in der Nachsorge des Rektumkarzinoms

Aim: The aim of this study was the assessment of positron-emission tomography (PET) with 18F-fluordesoxyglucose as a diagnostic tool in the follow-up of patients after resection of rectal carcinomas.Patients and Methods: 36 patients suspicious of tumor recurrence in the follow-up after primary R0-resection of a rectal carcinoma underwent a PET investigation. Indications for PET were rising CEA values, positive morphological imaging or doubtful clinical investigation. Histopathological results in case of reoperation, or the further clinical course of the patients in the next 12-month follow-up served to calculate sensitivity, specificity, as well as positive and negative predictive value of PET results.Results: In 23 patients tumor recurrence was verified by histopathology or clinical course (six local recurrences, eleven patients with distant metastases, six patients with both), 13 patients were free of tumor. In all patients with recurrent disease a true positive PET result was obtained, in eleven patients free of tumor PET was true negative, while two false positive PET results were documented. In both of these patients intraoperative findings revealed an inflammatory tumor after insufficiency of the rectal anastomosis, without evidence of carcinoma. Sensitivity for PET was 100%, specificity was 85%, positive predictive value was 92% and negative predictive value 100%.Conclusion: PET proved to be a valuable diagnostic tool in the follow-up of rectal carcinoma, with a high sensitivity and a good specificity. Indications for PET include the clinical suspicion for recurrence in combination with negative morphological imaging, and differential diagnosis of pelvic masses.     

Laparoscopic resection for diverticular disease

PURPOSE: The role of laparoscopic surgery in treatment of patients with diverticulitis is unclear. A retrospective comparison of laparoscopic with conventional surgery for patients with chronic diverticulitis was performed to assess morbidity, recovery from surgery, and cost. METHODS: Records of patients undergoing elective resection for uncomplicated diverticulitis from 1992 to 1994 at a single institution were reviewed. Laparoscopic resection involved complete intracorporeal dissection, bowel division, and anastomosis with extracorporeal placement of an anvil. RESULTS: Sigmoid and left colon resections were performed laparoscopically in 25 patients and by open technique in 17 patients by two independent operating teams. No significant differences existed in age, gender, weight, comorbidities, or operations performed. In the laparoscopic group, three operations were converted to open laparotomy (12 percent) because of unclear anatomy. Major complications occurred in two patients who underwent laparoscopic resection, both requiring laparotomy, and in one patient in the conventional surgery group who underwent computed tomographic-guided drainage of an abscess. Patients who underwent laparoscopic resection tolerated a regular diet sooner than patients who underwent conventional surgery (3.2±0.9vs.5.7±1.1 days;P<0.001) and were discharged from the hospital earlier (4.2±1.1vs.6.8±1.1 days;P<0.001). Overall costs were higher in the laparoscopic group than the open surgery group ($10,230±49.1vs.$7,068±37.1;P<0.001) because of a significantly longer total operating room time (397±9.1vs.115±5.1 min;P<0.001). Follow-up studies with a mean of one year revealed two port site infections in the laparoscopic group and one wound infection in the open group. Of patients undergoing conventional resection, one patient experienced a postoperative bowel obstruction that was managed nonoperatively, and, in one patient, an incarcerated incisional hernia developed that required urgent laparotomy. CONCLUSIONS: Laparoscopic resection in patients with chronic diverticulitis is safe, with faster recovery and shorter hospital stay compared with conventional open surgery. Higher cost of operating room usage time makes the laparoscopic technique difficult to justify economically. Simplification of operating room use and better case selection may improve cost-effectiveness of the laparoscopic approach.     

Prospective comparison of open<Emphasis Type="Italic">vs</Emphasis>. laparoscopic colon surgery for carcinoma

Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. METHODS: In 1990, we began a comparative study of open (OCR)vs.laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. RESULTS: Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7vs.9.7 days), less blood loss, less wound problems (1vs.14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. CONCLUSION: After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.     

Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer

PURPOSE: This study was undertaken to compare morbidity, mortality, and pathology after laparoscopically assisted right hemicolectomy (LARHC) or open right hemicolectomy (ORHC) for cancer of the right colon. METHODS: Patients undergoing either LARHC or ORHC for invasive carcinoma of the right colon during a 30-month period were studied. Data were collected from two sources. All morbidity, mortality, and pathology data were collected prospectively in a form suitable for computer storage and analysis as part of the ongoing Concord Hospital Colorectal Cancer Registry. Data concerning in hospital course were obtained by casenote review. RESULTS: Twenty-eight patients underwent LARHC, and 33 had an ORHC during the study period. The two groups were well matched with respect to age, sex, weight, associated comorbidities, and tumor stage. Mean operating room use time was significantly higher for LARHC (LARHC=261 minutes; ORHC=203 minutes;P<0.001). Mean hospital stay from date of resection was the same in both groups (LARHC=12 days; ORHC=12.2 days). There was no significant difference between procedures with respect to postoperative complications, return of gastrointestinal function, or narcotic analgesic requirements. There was a significant shorter distal margin of resection in the LARHC group (ORHC=13.4 cm; LARHC=10 cm;P=0.03.). Total cost was significantly greater for LARHC ($9,064vs.$7,881 (Australian);P<0.001). Median follow-up was 23.4 months for the LARHC group and 23.9 months for the ORHC group. To date, there have been no local or port site recurrences. CONCLUSION: Although there is no difference in morbidity and mortality following LARHC or ORHC, there is no apparent benefit for LARHC.     

Primärprävention beim Diabetes mellitus Typ 2

The increasing incidence of type 2 diabetes constitutes a considerable individual and socio-economic risk, therefore preventive concepts are urgently needed. Three prospective studies show that a “life-style-intervention” as well as drugs can prevent the development of diabetes as well as cardiovascular complications:The Diabetes Prevention Study (DPS) evaluated the influence of a “life-style-intervention”. The Diabetes Prevention Program (DPP) additionally examined the effect of metformin. In the Stop-NIDDM-Study acarbose was used for diabetes prevention and cardiovascular endpoints were also evaluated. The incidence of type 2 diabetes can be significantly reduced by a “life-style-intervention” and also by the administration of metformin or acarbose. With acarbose cardiovascular events are reduced significantly and comparably to a therapy with statins in primary prevention.     

Colorectal cancer in familial adenomatous polyposis

PURPOSE: This study was performed to determine the relationship among surgical treatment, colorectal cancer, and outcome in patients with familial adenomatous polyposis (FAP). METHODS: Records of 115 patients with FAP who underwent surgery at The Mount Sinai Medical Center between 1947 and 1994 were retrospectively reviewed. Patients without cancer were compared with those with colorectal cancer at initial surgery and with patients who developed rectal cancer following colectomy. RESULTS: Thirty-one patients (27 percent) had colorectal cancer at the time of initial surgery (colon=24; rectal=7). Another 11 patients (26 percent) developed rectal cancer after colectomy with ileorectal anastomosis (IRA). Mean age of patients with colorectal cancer at initial surgery was significantly higher than those without cancer (P <0.01). Patients who developed rectal cancer after IRA were significantly older than patients with colorectal cancer at initial surgery (P <0.01). All patients with rectal cancer after IRA had advanced disease with either nodal or distant metastases at the time of diagnosis. CONCLUSIONS: Colorectal cancer remains a major problem in the treatment of patients with FAP. Nearly one-fourth of these patients have colorectal cancer at initial operation, and one-fourth of patients with IRA develop rectal cancer after a mean follow-up of 13 years. Patients with rectal cancer following IRA are more likely to have advanced tumors than patients with colorectal cancer at initial operation. The high incidence and late stage of rectal cancer detected while under surveillance after IRA supports excision of the entire colorectal mucosa as the treatment of choice for most patients with FAP.     

<Emphasis Type="Italic">Per Anum</Emphasis> intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer

PURPOSE: The most important goal of sphincter-preserving operations for rectal cancer is to secure a distal surgical margin of safety and the anal sphincter. However, it is not always easy to transect the rectum and to secure a distal surgical margin of safety through the abdominal approach for tumors situated extremely low in the rectum. The aim of this study was to describe and to evaluate a new technique ofper anumintersphincteric rectal dissection and coloanal anastomosis. METHODS: The rectum, including the entire width of the internal anal sphincter, is transected circum ferentiallyviathe anal route to secure the surgical margin of safety under direct vision and is mobilized proximally as far as possible through the intersphincteric plane.Per anumcoloanal anastomosis is performed following transabdominal resection of the rectum. RESULTS: This technique has been used in 12 patients. There have been no instances of short-term or long-term anastomotic complications. CONCLUSIONS: This technique is safe when anastomosis must be performed at the dentate line. It is the best sphincter-preserving operation for lower rectal cancer and does not result in serious postoperative anal dysfunction.     

Undetectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype

PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mismatch repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary non-polyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples. MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of thehMLH1gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product.     

Analfissuren unter aggressiver Chemotherapie

Background: Hemato-oncologic patients who are subject to an aggressive chemotherapy often suffer from atypical anal fissures which are not diagnosed. The aim of this study is to present a case series study with 31 proctologic patients.Patients and Method: In 2001 and 2002 we examined 31 hemato-oncologic patients who suffered from anal pain which appeared during aplasia due to chemotherapy.Because of a similar history and more or less identical clinical findings we merged these patients to one collective.Results: We diagnosed acute and subacute anal fissures – partly at atypical location – and extensive cryptitides which differed from common anal fissures in the following criteria: 1. clinical picture like a beginning abscess, probably mitigated by antibiotics that are given during aplasia. 2. unusual morphologic extent. Pathologically, the cryptitis seems to play an important role.Conclusions: Before starting chemotherapy a proctologic examination should exclude an anal fissure or a cryptitis.This would allow to perform therapeutic measurements such us fissurectomy or cryptectomy during a non-aplasia intervall in order to avoid acute aggravation during aplasia.Therefore, cooperation between hematologists and proctologists is necessary.     

Relationship of curative surgery on natural killer cell activity in colorectal cancer

PURPOSE: Aim of this study has been to evaluate natural killer (NK) activity in patients with colorectal tumors before and after curative surgery. METHODS: Forty colorectal cancer patients without distant metastases were stratified according to American Joint Committee on Cancer/International Union Against Cancer staging system into three categories: Stage I (n = 12), Stage II (n = 15), and Stage III (n = 13). All of them underwent curative resection, and there were no major postoperative complications. Venous blood samples were obtained preoperatively, at surgical wound closure, and on the 1st, 7th, and 21st postoperative days. Mononuclear cells were isolated over Ficoll-Hypaque ^? (Lymphoprep, Nycomed Pharma AS, Oslo, Norway) gradients, and NK activity was assayed by evaluation of cytotoxic response against K562 cells. Normal NK activity was achieved from 15 healthy donors. Percentage relative increments in relation to preoperative levels were calculated for every postoperative sample, and t- test was used for statistical evaluation. RESULTS: Before surgery, Stages II and III patients had lower levels of NK activity than healthy people (P < 0.05 and P < 0.001, respectively). NK activity always fell after surgery (Stage I: -18.48±11.42; Stage II: ?16.93±13.57; Stage III: ?35.29±12.03, at day 1 postsurgery) and appeared to rise slightly by the 21st postoperative day in Stage I patients (+4.87±12.41). Stage II, and especially Stage III, patients did show a significant recovery by the 21st postoperative day (+23.63±9.36 and +43.19±13.34, respectively). At this time, NK activity in these two groups was not significantly lower than in normal subjects (P > 0.05). CONCLUSION: NK activity is depressed in colorectal cancer patients in relation to progression of illness, even at locoregional stages. Curative resection of tumors at Stages II and III has promoted a recovery of NK activity in patients with uneventful postoperative courses.