Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery: A Systematic Review and Proposal of a Standardization.

Objective: To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Background: Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized. Methods: A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases. Results: Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20-50) for open PD, 39 (11-60) for laparoscopic PD, 25 (8-100) for robotic PD (P = 0.521), 16 (3-17) for laparoscopic DP, and 15 (5-37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time -15%, blood loss -29%) whereas postoperative parameters improved later (second to third phase: complications -46%, postoperative pancreatic fistula -48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001). Conclusions: This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.

Long-term in vitro culture of hamster pancreatic ß-cells and induction of adenocarcinoma by treatment with N-nitrosobis(2-oxopropyl)amine.

OBJECTIVES: Earlier studies indicated that hamster pancreatic ductal adenocarcinoma not only derives from ductal/ductular structures but also from cells within the islet. So far unidentified cells within the islet are responsive to the carcinogenic effect of N-nitrosobis (2-oxopropyl) amine (BOP) forming poorly differentiated ductal adenocarcinoma. However, studies indicated a major role of ß-cells during carcinogenesis. To find out, if ß-cells are the primary target cells of BOP and if they are capable to form ductal adenocarcinoma after malignant transformation, we established a long-term culture of undifferentiated cells deriving from isolated ß-cells and treated them with BOP. METHODS: Langerhans' islets from pancreata of Syrian golden hamsters were isolated and dispersed into single cells by dispase digestion. Cells were labeled with a highly specific ß-cell surface antibody (K14D10) and these K14D10+ cells were extracted from the suspension by paramagnetic Dynabeads. Cells were cultured in vitro and treated with BOP. Untreated cells served as control. RESULTS: K14D10+ cells formed a monolayer and produced insulin over a period of 28 days in culture. However, with time in culture they became undifferentiated with a higher proliferation rate and after about 60 days in culture BOP treated cells showed anchorage independent growth. These cells autotransplanted s.c. formed a well-differentiated ductal adenocarcinoma. CONCLUSIONS: Pancreatic ß-cells are the primary target of BOP without necessarily being embedded in the compound of the Langerhans' islet. With time in culture, they give rise to undifferentiated cells and after malignant transformation they are able to form ductal adenocarcinoma.

Functional outcome after restorative proctocolectomy in pigs: comparing a novel transverse ileal pouch to the J-pouch and straight ileoanal anastomosis.

BACKGROUND: Restorative proctocolectomy followed by an ileoanal J-pouch procedure is the therapy of choice for patients with familial adenomatous polyposis and ulcerative colitis. After low anterior rectal resection, the authors have reported on a novel, less complex pouch configuration, a transverse coloplasty pouch. The aim of the present work was to apply this new design to the ileal pouch construction, to evaluate feasibility, and to measure functional results in comparison with the J-pouch and the straight ileoanal anastomosis using the pig as an animal model. METHODS: Twenty-three pigs underwent restorative proctocolectomy followed by reconstruction with straight ileoanal anastomosis (IAA; n = 5), J-pouch (n = 7), and a transverse ileal pouch (TIP; n = 11). Pigs were followed for 6 days postoperatively. Peristaltic function was assessed by manometry proximal to the pouch, in the reservoir, and at the level of the ileoanal anastomosis. Functional outcome was monitored by semiquantitative assessment of the general condition of the animals, postoperative feeding habits, and stool frequency and consistency. A Fourier analysis was performed in order to compare peristalsis in the ileal reservoirs. The reservoir volume was measured in situ by triple contrast computed tomography scan with 3D reconstruction. RESULTS: Seventeen animals survived for 1 week. There was no difference in the general condition or the feeding habits of the groups. A significant number of pigs with the TIP pouch (7/10) had semisolid or formed stools as opposed to liquid stools after J-pouch (6/6) and IAA (4/5; p = 0.01). TIP animals had a lower stool frequency (3.2 +/- 1.14 per day) on day 6 after the operation than pigs with J-pouch, 5.33 +/- 1,03, and IAA, 4.6 +/- 1.82 (p = 0.0036). The in situ volume of the pouches did not differ significantly. The Fourier analysis demonstrated a disruption of peristalsis by the J-pouch and the TIP reconstruction but not after IAA. CONCLUSION: The function of ileoanal reservoirs after proctocolectomy may result from the disruption of properistaltic waves after pouch formation. The mechanism of peristalsis disruption is independent of the in situ volume of the pouch.

Early results from a randomized clinical trial of colon J pouch versus transverse coloplasty pouch after low anterior resection for rectal cancer.

BACKGROUND: Patients with primary rectal cancer undergoing low anterior resection are often reconstructed using a pouch procedure. The aim of this trial was to compare colon J pouch (CJP) with transverse coloplasty pouch (TCP) reconstruction with regard to functional results, perioperative mortality and morbidity. As there is considerable uncertainty over the true anastomotic leak rate in patients with a TCP, the study analysed short-term outcome data. METHODS: Elective patients suitable for either procedure after sphincter-saving low anterior resection were eligible. Randomization took place during surgery. The primary endpoint was the rate of late evacuation problems after 2 years; secondary endpoints were anastomotic leak rate, perioperative morbidity and mortality. RESULTS: Between 21 October 2002 and 5 December 2005, 149 patients were randomized. All 76 patients randomized to TCP had the procedure compared with 68 of the 73 patients (93 percent) randomized to CJP. Both groups were comparable with regard to demographic and clinical characteristics. Surgical complications (CJP: 19 percent; TCP: 18 percent) and the overall anastomotic leak rate (8 percent) were equally distributed in both groups. CONCLUSION: This trial demonstrated a comparable early outcome for TCP and CJP. This contradicts previous reports suggesting a higher leak rate after TCP. REGISTRATION NUMBER: ISRCTN78983587 (http://www.controlled-trials.com).

Potential target antigens for immunotherapy in human pancreatic cancer.

BACKGROUND: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. METHODS: Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. RESULTS: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. CONCLUSIONS: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.

Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-gamma.

Pancreatic carcinoma is a very aggressive disease and little is known about its immunobiology. We here describe the presence in pancreatic cancer patients of spontaneously induced functional CD4 and CD8 memory/effector T cells reactive to autologous tumor cells or to the pancreatic cancer associated antigen, MUC-1. Such specific cells were present in the bone marrow or peripheral blood of most of the 23 tested patients. Low dose stimulation of primary cultures of pancreatic cancer cells with 500 IU/ml IFN-gamma for 72 h enhanced HLA-I expression and induced the de novo expression of HLA-II molecules. This led to a much better immune recognition by autologous HLA-I restricted and purified CD8 T cells and allowed tumor cell recognition by HLA-II restricted purified CD4 T-helper cells. Thus, interferon-gamma appears to be a useful adjuvant cytokine to enhance the immunogenicity of a patients' tumor cells and their recognition by tumor reactive immune cells.

The transverse coloplasty pouch.

BACKGROUND: The introduction of the total mesorectal excision (TME) and the use of modern staplers have improved outcome and increased the rate of sphincter-preserving low anterior resections in rectal cancer. Consequently, the interest in functional results after rectal reservoir reconstruction increased significantly. METHODS: A review of the current literature was conducted on the development of colon pouch procedures with a particular focus on the transverse coloplasty pouch compared with the colon J-pouch and other current techniques of reconstruction after TME such as the side-to-end anastomosis. RESULTS: The colon J-pouch (CJP) became the "gold standard" for rectal reservoir reconstruction owing to better early functional results compared with the straight coloanal anastomosis (CAA). However, 30% of the patients with CJP faced late evacuation problems requiring the chronic use of enemas or laxatives. This rate could be decreased by shortening the limb of the CJP from 8-10 to 5-6 cm, but the late evacuation problems remained in approximately 10% of the patients. An overview of the current knowledge on technical and functional aspects as well as indications and results of the transverse coloplasty pouch (TCP) is presented. CONCLUSION: The TCP was developed to provide early functional results comparable to the CJP while avoiding the late evacuation problems. Functional results after TCP, small colon J-pouch and side-to-end anastomosis are similar. Evacuation problems after TCP have not been reported.

Evacuation of neorectal reservoirs after TME.

Colon pouch reconstruction after deep rectal resection is functionally superior to straight colorectal/anal anastomosis. However, stool evacuation difficulties could jeopardize the functional benefit of neorectal reservoirs. Beside the well proven colon J-pouch, the transverse coloplasty pouch may represent a viable alternative. We examined evacuation and functional outcome after total mesorectal excision and transverse coloplasty pouch reconstruction. Thirty consecutive patients with cancer of the middle and distal third of rectum underwent a total mesorectal excision. In all patients, reconstruction was performed with a transverse coloplasty pouch. Pouch and anastomosis were checked by Gastrografin enema postoperatively. Eight months after surgery, video defecography, anal manometry and pouch volumetry were performed and the patients were interviewed according to a standardized continence questionnaire. Rectal resection and reconstruction with transverse coloplasty pouch anastomosis could be performed in all patients. No insufficiency of the pouch occurred. In the follow-up, no patient had difficulties to evacuate the pouch, none of these patients needed enemas or suppositories to facilitate defecation. All patients were continent for solid stools. Twenty-five of 27 patients had up to three bowel movements per day. Patients with reduced pelvic floor movement in the defecography proved more likely to suffer from urgency, fragmented evacuation and incontinence. Transverse coloplasty pouch reconstruction after total mesorectal excision is not associated with stool evacuation problems. Urgency and incontinence, which are rarely seen after this type of reconstruction, correlate with impaired pelvic floor movement rather than with pouch size or anal sphincter tonus.

Laparoscopic restorative proctocolectomy.

BACKGROUND: Restorative proctocolectomy is increasingly being performed using minimally invasive surgery. In published series laparoscopically assisted techniques have usually included a suprapubic incision to enable major parts of the operation to be done openly. METHODS: Fifty consecutive patients with familial adenomatous polyposis or ulcerative colitis underwent laparoscopic restorative proctocolectomy using only a small perumbilical incision of 4 cm or less for vascular dissection and pouch formation; all other steps were performed entirely laparoscopically. Logistic regression was used for statistical analysis. RESULTS: In four patients (8 per cent) the operation was converted to an open procedure. The diagnosis of ulcerative colitis was associated with a higher overall rate of complications (P = 0.011), and an increased body mass index (BMI) with a higher rate of major complications (P = 0.050). The occurrence of wound infection was related to the diagnosis of ulcerative colitis (P = 0.049). Conversion resulted in greater blood loss (P = 0.004), but not in a higher complication rate. No patient required a blood transfusion. Patients with an increased BMI and those taking immunosuppressive therapy had a longer hospital stay (P = 0.043). CONCLUSION: Laparoscopic restorative proctocolectomy is technically feasible. Patients with ulcerative colitis and increased BMI have a higher risk of complications. This minimally invasive technique may reduce the need for perioperative blood transfusion.

[The transverse coloplasty pouch after low anterior resection: early postoperative results]. / Transverser Koloplastik-Pouch nach tiefer anteriorer Resektion. Frühpostoperative Ergebnisse.

INTRODUCTION: A colon J pouch (CJP) still represents the standard rectal reservoir after low anterior resection. Though the CJP shows favourable early functional results, pouch evacuation problems tend to occur in the long term. The transverse coloplasty pouch (TCP), developed by our group allows comparable early functional results while avoiding evacuation problems. We report our experience with the TCP at the University Hospital of Heidelberg, Germany, and examine the risk of anastomotic leaks with this technique. METHODS: Between 1 October 2001 and 31 May 2003, 201 patients with rectal tumours underwent resection. Eighty-two patients with formation of TCP were enrolled in the study. RESULTS: During the creation of the TCP, no technical problems occurred, and the overall morbidity was 28%, including anastomotic leaks in seven patients (8.5%) and bleeding in two. The reoperation rate was 8.5%. An association between postoperative morbidity and preoperative radiation therapy could not be established. The hospital mortality rate was 3.6%. CONCLUSIONS: The use of TCP is a safe procedure which has gained worldwide acceptance in a short time, representing a technically straightforward procedure. Independently of patient size, habitus, and bulkiness of the colon, a TCP can always be performed after low rectal resection.

[Operative management in the treatment of pancreatic cancer]. / Operatives Management bei der Therapie des Pankreaskarzinoms.

The carcinoma of the pancreas is one of the 10 leading causes of death in the Western countries. Because of the resistance of pancreatic cancer against radiation and/or chemotherapy surgery is still the only possibility for cure. However, about 80 % of patients with the diagnosis of pancreatic cancer are no more suitable for curative resection at the time of diagnosis because of local tumor infiltration or the presence of distant metastases. This is one reason for the unsatisfactory situation in terms of 5-year-survival rate of 3 to 24 %. In resectable tumors of the pancreas head the standard Whipple dominates still as the surgical method of choice. However, the pylorus preserving Whipple has been established as a surgical alternative to the classical Whipple. Other surgical procedures like extended or regional pancreatic resections, predominantly done by Japanese surgeons seem to fit the concept of radical resection. But compared to the classical Whipple or the pylorus preserving Whipple resection there is still no clear advantage in terms of long term survival. The prospective European multicenter study ESPAC-1 firstly demonstrated a survival advantage for adjuvant chemotherapy (5-FU and folic acid) but no gain for radiochemotherapy in the treatment of patients with R0 or R1 resected pancreatic cancer in terms of prolongation of mean survival (19.7 months vs. 14.0 months).

The suprapubic approach for laparoscopic appendectomy.

BACKGROUND: Because it produces superior cosmetic results, patients prefer laparoscopic appendectomy over open appendectomy. We developed two alternative laparoscopic routes of access to the abdominal cavity for appendectomy that use suprapubic incisions placed below the line of pubic hair. We then compared the results for these three different modes of access. METHODS: Operative characteristics, morbidity, outcome, and patient preference regarding three different approaches to laparoscopic appendectomy were compared in a retrospective study. In addition, a group of 24 healthy women were surveyed by questionnaire about their preferred technique and expected cosmetic results. RESULTS: Between January 1997 and August 2000, 149 patients underwent laparoscopic appendectomy and were assigned to undergo one of the three techniques. Operative results, morbidity, and hospital stay were similar. Twenty-five percent of patients submitted to technique 1 (no suprapubic trocars) were satisfied with their method, vs 54% of patients with technique 2 (one suprapubic port, angled working trocars) and 100% of patients with technique 3 (two suprapubic parallel trocars). Almost all patients (92% of those who had technique 1 and 100% of those who had techniques 2 and 3) chose the standard laparoscopic access as the cosmetically least attractive method. All of the healthy controls we interviewed preferred technique 3. CONCLUSION: The placement of suprapubic trocars improves the surgeon's working position during laparoscopic appendectomy. A laparoscopic approach using two suprapubic trocars yields the best cosmetic results in the opinion of the majority of patients and healthy interviewees.

Mesenteric inflammatory veno-occlusive disease: a rare cause of intestinal ischemia. The first description of recurrent disease.

BACKGROUND: Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischemia of unknown etiology. Histologically, MIVOD is characterized by extended thrombophlebitis and fibrous organized thrombosis of multiple veins. The arteries are by definition not involved. Management includes surgery in all cases described. Recurrence has not been described until now. METHODS: We describe the case of a 64-year-old woman operated with the suspicion of intestinal ischemia. Clinical and histopathological characteristics are reported. RESULTS: The patient underwent a right hemicolectomy and segmental resection of the terminal ileum 15 months later for a recurrence. The histological examination of the resected specimen confirmed the diagnosis of MIVOD and a recurrence thereof. CONCLUSION: MIVOD is a rare cause of colonic ischemia. Recurrence of the disease, which is described here for the first time, is unusual after surgical resection.

A new surgical concept for rectal replacement after low anterior resection: the transverse coloplasty pouch.

OBJECTIVE: To analyze the feasibility, safety, complication and death rates, and early functional results of the transverse coloplasty pouch procedure after low anterior rectal resection and total mesorectal excision. SUMMARY BACKGROUND DATA: The authors previously developed a novel neorectal reservoir, the transverse coloplasty pouch, in an animal model; they report the first clinical data of a prospective phase 1 study. METHODS: Forty-one patients underwent low anterior rectal resection with total mesorectal excision for rectal cancer (n = 37) or benign pathology (n = 4). The continuity was restored with a transverse coloplasty pouch anastomosis, and the colon was defunctionalized for 3 months. Patients were followed up at 2-month intervals for functional outcome. RESULTS: Intraoperative complications occurred in three patients (7%), none related to the transverse coloplasty pouch. There were no hospital deaths and the total complication rate was 27% (11/41); an anastomotic leakage rate of 7% was recorded. The stool frequency was 3.4 per 24 hours at 2 months follow-up and gradually decreased to 2.1 per 24 hours at 8 months. Stool dysfunctions such as stool urgency, fragmentation, and incontinence grade 1 and 2 were regularly observed until 6 months; the incidence significantly decreased thereafter. None of the patients had difficulties in pouch evacuation. CONCLUSIONS: The transverse coloplasty pouch is a small-volume reservoir that can safely be used for reconstruction after sphincter-preserving rectal resection. The early functional outcome is favorable and can be compared to other colonic reservoirs. The concept of reducing early dysfunction seen after straight coloanal anastomosis and avoiding long-term problems of pouch evacuation is supported by this study. Future trials will compare the transverse coloplasty pouch with other techniques of restorative resections of the rectum.

Total mesorectal excision preserves male genital function compared with conventional rectal cancer surgery.

BACKGROUND: The introduction of total mesorectal excision (TME) has been shown to improve local recurrence rates in rectal cancer. The present study investigated the impact of this more extensive and radical procedure with regard to autonomic pelvic nerve function. METHODS: Patients with resected primary rectal cancer were interviewed by means of a questionnaire asking about preoperative and postoperative urinary bladder and genital function. The results in patients after rectal cancer surgery without TME (group 1; n = 29) were compared with those obtained after introduction of the TME technique (group 2; n = 31). Patients in group 2 were older and had a lower level of anastomosis than patients in group 1. Other patient, treatment and tumour characteristics were comparable between the groups. RESULTS: : Newly acquired and permanent symptoms of bladder dysfunction after rectal excision were present as follows (group 1 versus group 2): difficulty in bladder emptying 7 versus 19 per cent; sensation of incomplete bladder voiding 17 versus 17 per cent; urgency 17 versus 14 per cent; incontinence 10 versus 3 per cent; dysuria 7 versus 7 per cent; and dribbling 14 versus 8 per cent. Male patients stated the following sexual functions before operation/after operation in group 1 versus group 2: interest in sex 80 per cent/40 per cent versus 63 per cent/37 per cent; sexually active 67 per cent/7 per cent versus 53 per cent/22 per cent; impotence 75 per cent/6 per cent versus 58 per cent/26 per cent; ability to have intercourse 75 per cent/13 per cent versus 67 per cent/29 per cent; ability to achieve orgasm 88 per cent/13 per cent versus 76 per cent/47 per cent; and orgasm with ejaculation 88 per cent/9 per cent versus 76 per cent/53 per cent. CONCLUSION: While both conventional rectal cancer surgery and TME result in similarly favourable postoperative bladder function, both techniques decrease sexual function. However, TME offers a significant advantage with regard to preservation of postoperative sexual function in men and constitutes a true advance in rectal cancer surgery compared with conventional techniques.

Pylorus-preserving total pancreatectomy. Early and late results.

BACKGROUND/AIMS: Preservation of the pylorus is an accepted alternative procedure to the classical Whipple operation for pancreatic head resection but data describing its value for total pancreatectomy are sparse. METHODS: A prospective analysis of 22 total pancreatectomies performed in a consecutive series of 436 pancreatic resections from 1.11.93 to 1.5.99. RESULTS: 11 patients underwent total pancreatectomy with preservation of the pylorus. Histopathological examination revealed pancreatic adenocarcinoma in 16 cases and duodenal adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm. In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37 months (range 5-66). 62% of patients (n = 13) developed tumor recurrence and 13 patients died during the follow-up period with 10 deaths being cancer related. There was no difference concerning postoperative and follow-up morbidity of survival between patients undergoing pylorus-preserving total pancreatectomy or pancreatectomy with gastrectomy. However, postoperative body weight was increased 3, 6, 9 and 12 months following preservation of the pylorus. CONCLUSION: Total pancreatectomy with preservation of the pylorus is a feasible type of resection for all types of pancreatic or ampullary tumors, which shows a similar morbidity and long-term survival but improved nutritional recovery compared with standard total pancreatectomy.

Biological implications of tumor cells in blood and bone marrow of pancreatic cancer patients.

BACKGROUND: Patients with pancreatic cancer often have tumor recurrence despite curative resection. Cancer cells detected in blood or bone marrow at the time of diagnosis may relate to tumor stage and to prognosis. Recent research emphasis has centered on tumor cells in bone marrow aspirates, but whether these represent early micrometastases or blood-borne cells in transit is unknown. PATIENTS AND METHODS: We developed a specific immunocytochemical assay that evaluated more than 5.3 x 10(6) extracted mononuclear cells per sample of blood and bone marrow and that could identify a single tumor cell in that population. The assay was applied to samples of blood and bone marrow from 105 patients with pancreatic cancer and 66 controls. The prevalence of isolated tumor cells was compared with Union Internationale Contre le Cancer (UICC) stage. A multivariate Cox regression analysis for survival was performed. RESULTS: Pancreatic cancer cells were detected in 26% of blood samples and in 24% of bone marrow specimens. Specificity for cancer was 96%. The prevalence of isolated tumor cells in patients with proven resectable cancer was 9% in blood and 13% in bone marrow. The prevalence increased with UICC tumor stage in blood (P =.04) but not in bone marrow (P =.52) and correlated in blood with resectability (P =.02), progression of disease (P=.08), and peritoneal dissemination (P =.003). While survival correlated significantly with tumor stage (P <.001) and isolated tumor cells in blood correlated with tumor stage, the finding of cancer cells in blood or bone marrow, or both, was not independently associated with survival in patients with pancreatic cancer. CONCLUSIONS: Isolated tumor cells in blood but not bone marrow reflect the stage of growth and spread of pancreatic cancer, particularly in the peritoneal cavity. The findings are consistent with cells in bone marrow aspirates being in transit, not implanted. These disseminated cancer cells may be the consequence, rather than the cause, of progression.

Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal pancreatic cancer in rats.

OBJECTIVE: To investigate whether a high-fat/high-protein diet (HFPD) acts as a promoter of the natural course of cancer growth in the 7,12-dimethylbenzanthracene (DMBA)-induced ductal pancreatic cancer model in rats. SUMMARY BACKGROUND DATA: DMBA implantation to the rat pancreas induces ductal adenocarcinoma. Information regarding the effects of diet and the presence of K-ras mutation in this model is not available. METHODS: Rats were randomly assigned to regular rat chow or a diet with a 30% content in fat and protein (HFPD). The presentation of cancer, the histologic spectrum of neoplasia at 1 and 9 months, and the prevalence of cancer in relation to diet were assessed. Histologic specimens comprising normal ducts, hyperplasia, dysplasia/carcinoma in situ, or carcinoma were designated by a pathologist and microdissected. Genomic DNA was extracted, and K-ras and H-ras gene mutations were determined by a mutant-enriched polymerase chain reaction assay and direct sequencing. RESULTS: Rats fed HFPD increased their weight significantly compared with controls. DMBA induced characteristic stages of neoplasia at the implant site but not elsewhere. Macroscopic cancers of the pancreatic head presented regularly with common bile duct and gastric outlet obstruction. The prevalence of K-ras mutations was proportional to the degree of epithelial abnormality. K-ras mutations were significantly more frequent in cancer than in normal and hyperplastic ducts. H-ras mutations were not found. At 1 month in the HFPD-fed rats, the prevalence of cancer (16%) and dysplasia (16%) was not significantly different from the prevalence of cancer (29%) and dysplasia (8%) in the chow-fed rats. At 9 months the prevalence of cancer in the HFPD-fed rats increased to 29%, whereas that in the chow-fed rats decreased to 17%. The combined prevalence of cancer and dysplasia at 9 months in the HFPD-fed rats (34%) significantly exceeded that in the chow-fed rats. CONCLUSIONS: DMBA induces characteristic stages of neoplasia in the evolution of ductal pancreatic cancer in rats. K-ras mutations occur progressively in the ladder of oncogenesis, as in human pancreatic neoplasms. The addition of a diet with a high fat and protein content acts as a promoter of carcinogenesis, possibly by interfering with repair mechanisms and natural regression of early lesions.

[The transverse coloplasty pouch. Review of experimental data and clinical application]. / Dickdarmpouch durch transverse Koloplastik, Ubersicht experimenteller Daten und klinische Anwendung, Germany.

The transverse coloplasty pouch. Review of experimental data and clinical application. The transverse coloplasty pouch is a novel technique for sphincter preserving colonic reconstruction after total mesorectal excision. The method was developed in an animal model and resulted in favorable early functional results. Our results in patients with rectal cancer demonstrate that the technique is technically easy and safe. The transverse coloplasty pouch provides a neorectal reservoir of adequate volume and a favorable early functional outcome. It leads to a reduction in stool frequency compared with a straight anastomosis and the outcome is comparable to other colon reservoirs.