Planes of sharp pelvic dissection for primary, locally advanced, or recurrent rectal cancer.

In the design of operations for rectal cancers, the focus is often on circumventing the local extent of disease and leaving the pelvis free of cancer. The local extent of disease may range from minimal intramural invasion to the direct extension of a primary tumor to pelvic sidewall structures, e.g., the internal iliac vessels. In the absence of distant spread, understanding the planes of pelvic anatomy may allow the knowledgeable surgeon to cure patients who would otherwise be declared unresectable. We present the four planes (and one rare situation) available for sharp dissection which allow for the resection of all but a few cases of locally advanced disease.

Total mesorectal excision with autonomic nerve preservation: a new foundation for the evaluation of multi-disciplinary adjuvant therapy in the management of rectal cancers.

Local and distant recurrence rates and disease-free and overall survival are markedly improved by total mesorectal excision, with little increase in morbidity, compared with other techniques of resection of rectal cancer. Adjuvant therapy is associated with significant morbidity and initial results suggest it may not be beneficial in the aggregate. Adjuvant therapy must be re-evaluated in trials using TME as standard operative technique. Different subgroups of patients, defined by clinical and pathological criteria will be best served by different forms of therapy and should be studied based on rates of local and distant recurrence. Selected groups of patients will be best served by undergoing no adjuvant therapy of any kind.

Pudendal neuropathy is the only parameter differentiating leakage from solid stool incontinence.

PURPOSE: Fecal incontinence may occur in several forms. Although some patients are grossly incontinent, other patients experience only leakage. In patients with gross incontinence, severity can range from the mildest forms (limited to loss of control of flatus) to the most severe forms (involving loss of solid stool). This study was undertaken to determine which physiologic parameters differentiate female patients with incontinence of solid stool from patients with control of formed stool and incontinence limited to seepage. METHODS: Thirty-eight consecutive female patients with a primary complaint of seepage or solid stool incontinence were evaluated using water perfusion manometry, balloon inflation assessment of rectal sensitivity, and pudendal nerve terminal motor latency. A prospectively maintained database was used for collection of data. The findings in the two patient groups were compared with patients in a group of normal control individuals. Ages of the women in the three groups were similar. RESULTS: Both groups of patients demonstrated statistically significant (P < 0.05) decreases in rest and squeeze sphincter lengths, pressures, and pressure volumes compared with normal volunteers. The patients also had significantly more asymmetric high-pressure zones and hypersensitive rectums. No significant difference between the two groups of incontinent patients could be identified using any of these parameters. Significant differences between the groups were found in pudendal nerve function. The distal rectoanal excitatory reflex was abnormal in 58.1 percent of grossly incontinent women compared with 28.6 percent of patients with leakage (P < 0.05). The majority of patients with leakage alone (65 percent) had normal pudendal nerve terminal motor latency, whereas only 22.6 percent of women with gross fecal incontinence had normal pudendal nerve terminal motor latency bilaterally (P = 0.01). CONCLUSIONS: Normal bilateral pudendal nerve function can partially compensate for abnormal sphincter symmetry and function, permitting women with grossly abnormal parameters to maintain control of bowel movements. It remains to be seen whether, with advancing age, patients with leakage will have development of slowed pudendal nerve conduction and, if so, whether their condition will progress to gross incontinence.

The role of p53, p21WAF1/C1PI, and bcl-2 in radioresistant colorectal carcinoma.

Genetic alterations in the p53 tumor suppressor gene are common in human colorectal cancers, occurring in approximately 70% of tumors. In vitro studies have shown that wild-type p53 is involved in controlling cell cycle checkpoint functions and apoptosis involved in the cytotoxic response induced by ionizing radiation and several anticancer chemotherapeutic agents. Wild-type p53 protein can transcriptionally activate the WAF gene, which encodes a cyclin-dependent kinase inhibitory protein, p21WAF1/C1PI protein, and transcriptionally repress the bcl-2 gene, which encodes an inhibitor of apoptosis. To learn more about the in vivo relationship between p53 protein and the expression of p21WAF1/C1PI and bcl-2 proteins in human colorectal cancers treated with radiation therapy, we examined the expression of these proteins by immunohistochemistry in pre-irradiated biopsy specimens and surgical specimens with residual tumor of 27 patients with colorectal carcinoma. Cell proliferation was measured using Ki-67 expression in the tumor cells. The p53 protein was not detected in normal colorectal mucosa, but it was expressed in 21 of 27 (78%) of pre-irradiated tumor samples and in 19 of 27 (70%) of post-irradiated tumors. Expression of the bcl-2 protein in normal colorectal mucosa was confined to the basal epithelial cells of the crypts. Diffuse bcl-2 staining was detected in tumor cells in 13 of 27 (48%) of pre-irradiated samples and in 14 of 27 (52%) of post-irradiated samples. p21WAF1/C1PI expression was detected in 14 of 27 (52%) of pre-irradiated samples but only in 7 of 27 (26%) of post-irradiated samples. No inverse relationship between expression of p53 protein and abnormal bcl-2 expression was apparent. p21WAF1/C1PI was expressed in most nonproliferating Ki-67-negative epithelial cells at the apical tips of the crypts in normal colorectal mucosa, but not in proliferating Ki-67-positive cells of adjacent adenomatous mucosa. An inverse relationship between Ki-67 and p21WAF1/C1PI expression was observed in normal colorectal mucosa and adjacent adenomatous mucosa. After radiation therapy, p53 protein accumulation did not change among residual tumors in 18 cases (three of which were initially negative and remained negative); in four cases there was a significant increase, and five cases had a substantial decrease of p53 expression. Aberrant bcl-2 expression is not correlated with expression of p53 and does not increase significantly in post-irradiated tumor cells. p21WAF1/C1PI expression is markedly reduced in tumor cells that survive radiation therapy.

Endoscopic management of malignant colorectal polyps.

Malignant polyps are adenomatous polyps that contain cancerous cells that have penetrated the muscularis mucosae. Pedunculated malignant polyps that have not yet developed to level 4 invasion and have no other adverse histopathologic criteria have a high likelihood of cure by endoscopic excision alone. However, if level 4 invasion has been reached or if any additional adverse characteristic, such as poor differentiation, lymphatic or venous invasion, or close or involved margins, is present, the risk of inadequate treatment from endoscopic excision alone becomes appreciable. Under such circumstances, a definitive resection is favored unless the increased risk of recurrence is offset by age-related limited life expectancy or substantial comorbidities. Sessile malignant polyps are more likely to demonstrate level 4 invasion. In addition, these lesions are often less satisfactorily treated by endoscopic excision. In most circumstances, unless patient factors contraindicate intervention, resection should be performed.

Acute pancreatitis secondary to incarcerated paraesophageal hernia.

Paraesophageal hiatus hernia can be a morbid and even lethal condition. Although many complications from this entity have been described, they almost always involve gastric incarceration and its related complications. Occasionally, the transverse colon or spleen may be involved in the hernia, causing additional symptoms. An unusual case of paraesophageal hiatus hernia involving incarceration of the pylorus, proximal duodenum, and pancreatic head is described. The patient's presentation, operative management, and perioperative course are discussed to emphasize the importance of early elective repair of paraesophageal hiatus hernia before the development of such occurrences.

Affinity labeling of rat liver carbamyl phosphate synthetase I by 5'-p-fluorosulfonylbenzoyladenosine.

The ATP analog 5'-p-fluorosulfonylbenzoyladenosine (FSBA) has been used to study the interaction of MgATP with rat liver carbamyl phosphate synthetase I. Incubation of the enzyme with concentrations of FSBA as low as 0.025 mM produced considerable inactivation (41% at 120 min); identical rates and extents of reaction were produced by 0.5, 1, and 2 mM FSBA. Of the substrates for carbamyl phosphate synthetase I, only MgATP protected against FSBA inactivation. In the presence of a constant concentration of MgATP, increasing the FSBA concentration led to increased inhibition. Conversely, an increase in MgATP concentration led to decreased inhibition from a constant concentration of FSBA. Other nucleotide triphosphates provided no protection against FSBA inactivation. Addition of dithiothreitol to the FSBA-inactivated enzyme led to partial reactivation, suggesting that cysteine residue(s) were involved in the FSBA reaction. 5,5'-Dithiobis(2-nitrobenzoic acid) titration of the free sulfhydryl groups on the enzyme confirmed that cysteine residues were involved in reaction with FSBA; titration of the enzyme after incubation in the absence and presence of FSBA yielded values of 21 and 18(+/- 1), respectively. Binding studies with 5'-p-fluorosulfonylbenzoyl[2-3H]adenosine indicated that: 4 amino acid residues were involved in reaction with FSBA; 2 of these reaction sites were cysteine residues and 2 were noncysteine residues; MgATP protected one of the cysteine residues and one of the noncysteine residues from reaction with FSBA; the MgATP-protected noncysteine residue is essential for fully activity. These data strongly suggest that FSBA is an affinity label for two distinct MgATP sites on carbamyl phosphate synthetase I.