Outcome of Rectal Cancer Surgery After the Introduction of Preoperative Radiotherapy in a Low-Volume Hospital

Background

The improvement in local control by preoperative radiotherapy for rectal cancer can be at the cost of substantial morbidity.

Aim of the Study

The aim of this study was to determine the impact of short-course preoperative radiotherapy on morbidity and mortality after total mesorectal excision in a low-volume hospital.

Methods

From 2000 to 2007, 104 patients underwent rectal resection for a proven malignancy. Outcome parameters including anastomotic leakage rate, duration of hospital stay, and survival were retrospectively compared between patients who received radiotherapy followed by resection and patients who underwent resection alone.

Results

Anastomotic leakage occurred in 11 of 28 patients (39%) who underwent radiotherapy and in 10 of 54 patients (19%) in the surgery-alone group (P?=?0.04). The length of hospital stay was significantly longer in the radiotherapy group in comparison with the surgery-alone group (median 22 vs. 12 days; P?=?0.002). Independent predictors of decreased overall survival were high American Society of Anesthesiologists classification, application of preoperative radiotherapy, necessity of Intensive Care Unit admission, and advanced pathological stage.

Conclusions

A negative impact of preoperative radiotherapy on morbidity and mortality after rectal cancer surgery with an annual caseload of 16 was observed. Auditing of local practices is essential for quality control and potential improvement of clinical outcome.     

The role of transsphincteric pressure and proximal gastric volume in acid reflux before and after fundoplication

BACKGROUND & AIMS: This study was conducted to explore the role of proximal gastric volume and transsphincteric pressure on acid reflux during transient lower esophageal sphincter relaxation (TLESR) in patients with gastroesophageal reflux disease (GERD) both before and after laparoscopic fundoplication. METHODS: Twenty GERD patients were studied before and after fundoplication along with 20 healthy controls. High-resolution manometry and pH recording was performed for 1 hour before and 2 hours following meal ingestion (500 mL/300 kcal). Three-dimensional ultrasonographic images of the stomach were acquired before and every 15 minutes after meal ingestion. RESULTS: Postprandial proximal to total gastric volume distribution ratios were significantly larger in GERD patients before fundoplication (0.57 +/- 0.01; P < .05) and smaller following fundoplication (0.37 +/- 0.01; P < .001) compared with controls (0.46 +/- 0.01). The percentage of TLESRs associated with acid reflux did not relate to proximal gastric volume in any subject group. The transsphincteric pressure profile was different for TLESRs with and without reflux in GERD patients as well as in healthy controls. The pressure gradient across the esophagogastric junction (EGJ) (DeltaEGJp) was greater for TLESRs with acid reflux compared with TLESRs without acid reflux in both GERD patients (11.4 +/- 0.8 vs 8.0 +/- 0.5 mm Hg, respectively; P < .01) and controls (10.6 +/- 0.7 vs 7.1 +/- 0.8 mm Hg, respectively; P < .05). After fundoplication, DeltaEGJp during TLESRs was 7.9 +/- 0.9 mm Hg, and the transsphincteric pressure profile markedly changed. CONCLUSIONS: Although proximal gastric volume plays a key role in eliciting TLESRs, it is not related to the incidence of acid reflux during TLESRs. The transsphincteric pressure gradient is greater in TLESRs associated with acid gastroesophageal reflux.     

Probiotic treatment with Probioflora in patients with predicted severe acute pancreatitis without organ failure

BackgroundWe previously demonstrated that probiotic prophylaxis, in patients with predicted severe pancreatitis, did not prevent infectious complications but unexpectedly increased the risk of bowel ischemia and mortality. The suggestion that these negative findings are only observed in the presence of organ failure at the start of probiotic treatment has not been confirmed.MethodsIn a retrospective analysis, all patients with predicted severe acute pancreatitis without initial organ failure admitted to a medium care facility of a teaching hospital in Prague from January 2003 to December 2010 were included. All patients routinely received probiotic treatment with Probioflora. Total parenteral nutrition (TPN) was routinely started and shifted toward total enteral nutrition. Infectious complications, mortality and the incidence of bowel ischemia were recorded.Results99 consecutive patients, mean age 56 years, were included. Infectious complications occurred in 42 patients (42%), consisting of bacteremia (n = 40), pneumonia (n = 11) and infected necrosis (n = 11). Bowel ischemia was detected in two patients (2%). Overall mortality was 8%.ConclusionIn this retrospective study no apparent positive or negative impact of probiotic treatment with Probioflora was demonstrated when administered to patients with predicted severe acute pancreatitis without initial organ failure.     

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4- hydroperoxycyclophosphamide-purged bone marrow

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

The effect of posterior rectopexy on fecal continence

Twenty-three patients with rectal prolapse or intussusception were studied to specifically focus on the effect of posterior rectopexy on fecal continence, anal pressure, and rectal capacity. Before operation, five patients were fully continent (A), 10 were continent for solid stools (B) and eight patients were fully incontinent (C). Group A remained fully continent; continence was regained nine times in group B and in group C, three patients regained full continence, two became continent for solid stools, three patients remained incontinent. Other symptoms such as constipation, false urgency, and a feeling of incomplete evacuation were not beneficially influenced by rectopexy. The patients' continence status was correlated to anorectal manometry and rectal capacity measurement. In group B, incremental pressure (P=squeeze — basal P) increased significantly (P<0.02) as well as incremental volume (V=maximum tolerated volume-volume of first sensation) (P<0.05). We conclude that, by an increase of incremental anal pressure and incremental rectal volume, posterior rectopexy offers an 83 percent chance of regaining full continence, or a major improvement, and a 17 percent chance of stabilization of fecal incontinence.Read at the spring meeting of the British Society of Gastroenterology, Bradford, April 1989.     

Prospective evaluation of 24 hour ambulatory pH metry in Belsey Mark IV antireflux surgery.

This study evaluated the effect of the 270 degrees Belsey Mark IV fundoplication on 24 hour ambulatory pH metry variables. Thirty seven patients with confirmed gastro-oesophageal reflux disease who had a Belsey Mark IV antireflux procedure were evaluated preoperatively and three to six months postoperatively including endoscopy, lower oesophageal sphincter manometry, and 24 hour ambulatory pH metry. In 30 of 37 patients the Belsey Mark IV fundoplication was judged successful based on symptom relief and healing of oesophagitis. In these 30 patients percentage reflux for total, upright, and supine time (median and range) decreased significantly (p < 0.001) from 10.0% (2.7-35.3%), 10.8% (3.2-39.9%), and 6.7 (0.0-33.0%) respectively to 0.5% (0.0-7.4%), 0.6% (0.0-13.7%), and 0.1% (0.0-4.9%) after operation. This decrease in reflux time resulted predominantly from a significant (p < 0.001) reduction in the number of reflux episodes from 98 (23-231) to 14 (0-82) postoperatively. Normalisation of total reflux time (upper limit of normal for time with pH below 4:4%) was found in 89% and normalisation of total and upright and supine reflux in 64% of successfully operated patients with confirmed abnormal acid reflux before operation. A successful antireflux procedure was associated with significant (p < 0.001) increases in lower oesophageal sphincter pressure from 7.8 (0.6) mm Hg to 14.5 (0.7) mm Hg mean (SEM). In seven patients with a failed antireflux operation basal lower oesophageal sphincter pressure did not change significant;y (preoperative value 5.7 (1.3) mm Hg; postoperative value 7.8 (0.8) mm Hg). In these patients reflux time did not decrease after the operation and remained in the abnormal range in all patients. It is concluded that a successful, in contrast with a failed, Belsey Mark IV fundoplication is associated with significant decreases in total, upright, and supine reflux time. Normalisation of pH metry variables is not a prerequisite for successful antireflux surgery. A surgery. A successful 270 degree Belsey Mark IV fundoplication was associated with a significant increase in basal lower oesophageal sphincter pressure, in contrast with the failure group. Restoration of a sufficient lower oesophageal sphincter barrier is an important aim in antireflux surgery.     

Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.     

Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4- hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.