Is there a role for specialized geriatric centers in treating geriatric cancer patients?

As the population with colorectal cancer ages, the tailored approach required to manage older patients becomes all the more important for all providers and institutions treating colorectal cancer to adopt and improve the outcomes and well-being of this important and increasingly prevalent population. Joint guidelines from the American College of Surgeons and American Geriatric Association should be followed. Older cancer patients undergoing colorectal cancer surgery should be referred to centers with expertise in minimally invasive surgery. Likewise, older rectal cancer patients should be referred to centers with expertise in treating rectal cancer.

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer.

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.

Electrothermal bipolar vessel ligation improves operative time during laparoscopic total proctocolectomy: a large single-center experience.

BACKGROUND: Laparoscopic total proctocolectomy (TPC) with or without ileoanal pouch is a major operation for which the traditional benefits of laparoscopy were not immediately apparent, in part due to the longer operating times. The use of energy devices has been shown to improve operative outcomes for patients who undergo laparoscopic segmental colectomies, but there are limited data for laparoscopic TPC (LTPC). METHODS: All patients who underwent LTPC between January 2002 and July 2011 were identified from a prospectively maintained institutional-review-board-approved database. Univariate and multiple linear regression analyses were performed to assess the impact of electrothermal bipolar vessel sealers (EBVS) for vessel ligation on operative time. Secondary outcomes included vessel ligation failures, estimated blood loss, and other intra- and postoperative outcomes. RESULTS: One hundred and forty-five patients underwent LTPC, including 126 restorative ileoanal pouch and diverting ileostomy operations and 19 TPC and end ileostomy procedures. Fifteen percent of LTPCs were totally laparoscopic, 45 % were laparoscopic-assisted, 32 % were hand-assisted, and 8 % were laparoscopic-converted cases. Laparoscopic vessel ligation was performed using EBVS (76 %), endoscopic staplers (12 %), or hybrid techniques (12 %). Vessel ligation groups were similar in demographics, body mass index, surgical indication, immunosuppression, and prior surgery. EBVS were associated with shorter median operative times (247 vs. 290 vs. 300 min, p = 0.018) and fewer vessel ligation failures (1 vs. 11 vs. 12 %, p = 0.027) compared with endoscopic staplers and hybrid techniques, respectively. There were no differences in estimated blood loss and intra-operative complications among the three groups. Length of stay, 30-day morbidity, and 30-day re-operation rates were also similar. On multiple linear regression analysis, EBVS were a significant predictor of operative time (p = 0.019). CONCLUSIONS: Routine use of electrothermal bipolar vessel ligation for LTPC is associated with shorter operative time and fewer vessel ligation failures without higher risk of complications than other vessel control methods.

Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis.

We have shown that neurokinin A-induced contraction of human sigmoid circular muscle (HSCM) is reduced in patients with ulcerative colitis and that interleukin (IL)-1beta may play a role in this change. We now examine changes in the signal transduction pathway mediating neurokinin A-induced contraction of HSCM and explore the role of IL-1beta and of H(2)O(2) in these changes. In Fura 2-AM-loaded ulcerative colitis HSCM cells, neurokinin A- and caffeine-induced peak Ca(2+) increase and cell shortening were significantly reduced. In normal cells, neurokinin A-induced contraction was decreased by protein kinase C inhibitor chelerythrine and by calmodulin inhibitor CGS9343B [1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate]. In ulcerative colitis muscle cells, contraction was inhibited only by chelerythrine but not by CGS9343B. IL-1beta treatment of normal HSCM strips and cells reproduced the changes observed in ulcerative colitis. IL-1beta-induced reduction in caffeine-induced peak Ca(2+) increase and contraction was reversed by catalase, suggesting a role of H(2)O(2). IL-1beta-induced H(2)O(2) production was inhibited by mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) and by cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3 (arachidonyltrifluoromethyl ketone), but neither by p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] nor by nuclear factor-kappaB (NF-kappaB) inhibitory peptide NF-kappaB SN50 (H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH). IL-1beta significantly increased the phosphorylation of extracellular signal-regulated kinase 1 (ERK1)/ERK2 MAPKs and cPLA(2) and IL-1beta-induced cPLA(2) phosphorylation was blocked by PD98059. We conclude that Ca(2+) stores of HSCM cells may be reduced in ulcerative colitis and that the signal transduction pathway of neurokinin A-induced contraction switches from calmodulin- and protein kinase C-dependent in normal cells to protein kinase C-dependent in ulcerative colitis cells. IL-1beta reproduces these changes, possibly by production of H(2)O(2) via sequential activation of MAPKs (ERK1/ERK2) and cPLA(2).

Gracilis muscle transposition for iatrogenic rectourethral fistula.

OBJECTIVE: To assess the utility of gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula. SUMMARY BACKGROUND DATA: Iatrogenic rectourethral fistula poses a rare but challenging complication of treatment for prostate cancer. A variety of procedures have been described to treat this condition, none of which has gained acceptance as the procedure of choice. The aim of this study was to review the authors' experience with gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula. METHODS: A retrospective chart review of all patients who underwent gracilis muscle transposition for iatrogenic rectourethral fistula was performed, and follow-up was established by telephone interview. Successful repair was defined as absence of a fistula after reversal of fecal and urinary diversions. RESULTS: Eleven men, mean age of 62 years, underwent 12 gracilis muscle transpositions for rectourethral fistula between 1996 and 2001. Six patients had a history of pelvic radiotherapy, and five patients had previous failed attempts to repair the fistula. In nine patients, the fistula healed following gracilis muscle transposition. One patient developed a rectocutaneous fistula that healed with fibrin glue injection, and one developed perineal sepsis requiring debridement of the transposed gracilis. This patient underwent a second gracilis transposition, which uneventfully healed. Overall, all of the patients had closure of their diverting stomas and maintained healed rectourethral fistulas. There were no intraoperative complications, and the only long-term complication of this procedure was mild medial thigh numbness in two patients. CONCLUSIONS: Gracilis muscle transposition is an effective surgical treatment for iatrogenic rectourethral fistula. It is associated with low morbidity and a high success rate.

Current controversies in pouch surgery.

Restorative proctocolectomy with ileal pouch anal anastomosis has become the most commonly used procedure for elective treatment of patients with mucosal ulcerative colitis and familial adenomatous polyposis. Since its original description, the procedure has been modified in an attempt to obtain optimal functional results with low morbidity and mortality, and yet provide a cure for the disease. These modifications of the technique are discussed in this review, limited to the current points of controversy. We reviewed the current literature describing restorative proctocolectomy with ileal pouch anal anastomosis. The current "hot topics" for debate are transanal mucosectomy with hand-sewn anastomosis versus the double-stapled technique, the use of diverting ileostomy, indeterminate colitis, the role of laparoscopy, and indications for pouch surgery in the elderly. Longer follow-up of patients and increased knowledge and experience with pouch surgery, coupled with active prospective evaluation of the procedure are required to settle these issues. Patients must be fully informed to understand inherent risks of each choice.

The safety and efficacy of the artificial bowel sphincter for fecal incontinence: results from a multicenter cohort study.

PURPOSE: The aim of this trial was to evaluate the safety, efficacy, and impact on quality of life of the Acticon trade mark artificial bowel sphincter for fecal incontinence. METHODS: A multicenter, prospective, nonrandomized clinical trial was conducted under a common protocol. Patients were evaluated with anal physiology, endoanal ultrasonography, a fecal incontinence scoring system, fecal incontinence quality of life assessment, and overall health evaluation. Patients with a fecal incontinence score of 88 or greater (scale, 1-120) were considered candidates for the study. Implanted patients underwent identical reevaluation at 6 and 12 months postimplant. RESULTS: One hundred twelve of 115 patients (86 females) enrolled were implanted. Mean age was 49 (range, 18-81) years. A total of 384 device-related or potentially device-related adverse events were reported in 99 enrolled patients. Of these events, 246 required no intervention or only noninvasive intervention. Seventy-three revisional operations were required in 51 (46 percent) of the 112 implanted patients. Infection rate necessitating surgical revision was 25 percent. Forty-one patients (37 percent) have had their devices completely explanted, of which 7 have had successful reimplantations. In patients with a functioning neosphincter, improvement in quality of life and anal continence was documented. Mean matched fecal incontinence scores in 63 patients at 6 months follow-up was improved from 105 preimplant to 51 postimplant. In 55 patients at 12 months follow-up, mean matched fecal incontinence scores were 105 preimplant 48 postimplant. A successful outcome was achieved in 85 percent of patients with a functioning device. Intention to treat success rate was 53 percent. CONCLUSIONS: Although morbidity and the need for revisional surgery are high, the artificial bowel sphincter can improve anal incontinence and quality of life in patients with severe fecal incontinence.

A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures.

PURPOSE: The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures. METHOD: A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation. RESULTS: There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related. CONCLUSION: Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures.

Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines.

HYPOTHESIS: Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC. DESIGN: Cohort analytic study. SETTING: Research laboratory in a tertiary academic medical center. PARTICIPANTS: Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC. INTERVENTIONS: An enzyme-linked immunosorbent assay was used to measure IL-l beta. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca(2+) (calcium) concentrations were measured by standard techniques. MAIN OUTCOME MEASURE: Effects of IL-1 beta on smooth muscle function in normal and UC colons. RESULTS: In patients with UC, IL-1 beta was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2-loaded cells from patients with UC, the NKA-induced Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase. CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.