Adrian J. Greenstein

Extraintestinal cancers in inflammatory bowel disease

The case histories of 1961 patients with inflammatory bowel disease (IBD), 1227 with Crohns disease (CD) and 734 with ulcerative colitis (UC), have been studied for the incidence of extraintestinal malignant neoplasms. There were 54 extraintestinal cancers in 51 patients: 28 patients with CD and 23 with UC; 25 men and 26 women. There were 9 breast, 7 skin, 15 reticuloendothelial, 11 genitourinary, 3 lung, 3 perianal, 2 pancreatic islet cell, and several miscellaneous cancers. The number of patient‐years from the onset of disease to the last date of follow‐up was calculated for men and women with each form of IBD. The observed number (O) of neoplasms was recorded. The expected number (E) of neoplasms was derived from the Department of Health, Education, and Welfare (DHEW) incidence figures for the same neoplasms that occurred in a standard age‐ and sex‐matched population. The O/E ratio was then calculated for each type of cancer as well as for the entire series. There were no statistically significant increases in overall O/E ratios of extraintestinal cancers for either CD (0.76) or UC (1.32). On the other hand, several specific types of cancer did appear to occur with a frequency that was significantly greater than expected. These cancers were classified into two groups. The first group included reticuloendothelial neoplasms. There was an excess of leukemias in UC (P < 0.005) and an excess of lymphomas in both UC and CD (P < 0.005). The second group included three squamous cell cancers of the perianal region, an incidence 30 times greater than expected, and two squamous cell cancers of the vagina, also in excess of the expected number. Lymphoma, leukemia, and squamous cell cancers have been reported to occur in excess in immunosuppressed or irradiated patients. It may therefore be speculated that the apparently increased incidence of these neoplasms in the patients with ileitis and colitis might be related to immunologic deficiencies associated with IBD, to the long‐term administration of steroids or other immunosuppressive medications that were given to most of the patients or, possibly, to increased exposure to ionizing radiation. The apparently increased incidence of perianal and vaginal cancers of the squamous variety might be a consequence of the combined effects of chronic inflammatory disease involving these areas and primary immune suppression.

Small bowel carcinoma in crohn's disease. Distinguishing features and risk factors

An 86‐year‐old woman who developed small bowel adenocarcinoma 40 years following in‐continuity bypass of a 60‐cm segment of regional ileitis represents the 22nd reported patient with this complication of bypassed Crohns disease. Her case demonstrates several of the typical clinical features of such cancers: late recrudescence of disease following a 40‐year period of relative quiescence; delayed diagnosis due to misinterpretation of the clinical picture (intestinal obstruction, abdominal mass, intraabdominal abscess, and fistula formation) as due to inflammatory bowel disease; and an exceedingly poor prognosis with rapid widespread local dissemination and death. Histologically, severe dysplasia was demonstrated both in close proximity to and at a distance from the lesion. The increasing number of case reports of adenocarcinoma arising at the site of long‐standing Crohns disease, many with dysplasia within areas of diseased bowel, is further evidence that Crohns disease is a precancerous condition. Physicians must continue to search for methods of earlier diagnosis to improve the prognosis of small bowel carcinoma in Crohns disease.

Laparoscopic subtotal colectomy for medically refractory ulcerative colitis: the time has come.

PurposeTo evaluate laparoscopic versus open subtotal colectomy (STC) in patients with ulcerative colitis (UC) requiring urgent or emergent operative intervention.MethodsA retrospective review was performed of 90 patients with medically refractory UC who underwent STC with end ileostomy at The Mount Sinai Medical Center from 2002 to 2007. Patients with toxic megacolon were excluded. Univariate analysis was conducted by unpaired Student t-test and chi-square test. Results are presented as meanxa0±xa095% confidence interval.ResultsNinety patients underwent STC, 29 by laparoscopic and 61 by open approach. In patients undergoing laparoscopic versus open STC, intraoperative blood loss was decreased (130.4xa0±xa038.4 vs. 201.4xa0±xa043.2xa0ml, pxa0<xa00.05) and operative time prolonged (216.4xa0±xa020.2 vs. 169.9xa0±xa014.4xa0min, pxa0<xa00.01). In the absence of postoperative complication, hospital length of stay (4.5xa0±xa00.7 vs. 6xa0±xa01.3xa0days, pxa0<xa00.001) was shorter in laparoscopic versus open group. No mortalities occurred. Overall morbidity, 30-day readmission, and reoperation were equivalent regardless of operative approach. Wound complications were absent in the laparoscopic group compared with 21.4% in the open group (pxa0<xa00.01). Follow-up at a mean of 36xa0months demonstrated no difference in restoration of gastrointestinal continuity.ConclusionLaparoscopic STC confers the benefits of improved cosmesis, reduced intraoperative blood loss, negligible wound complications, and shorter hospital stay. Laparoscopy is a feasible and safe alternative to open STC in patients with UC refractory to medical therapy requiring urgent or emergent operation.

Management of asparaginase induced hemorrhagic pancreatitis complicated by pseudocyst

Asparaginase induced hemorrhagic pancreatitis is a rare but serious development occurring in less than 0.5% of patients treated with this drug. Severe pancreatitis with progressive abdominal distention, toxemia, hypotension and respiratory insufficiency occurred in an 18‐year‐old patient with acute lymphoblastic leukemia following treatment with asparaginase. There was a dramatic response to high flow peritoneal lavage with rapid recovery within 24 hours from a moribund state. The subsequent development of a pseudocyst, with progressive increase in size and development of obstructive symptoms, required surgical decompression. Transgastric cystogastrostomy was successfully carried out. Cancer 43:718–722, 1979.

Surgical Management and Outcomes of Patients with Duodenal Crohn's Disease

BACKGROUNDnDuodenal Crohns disease (DCD) has been reported to occur in 0.5% to 4% of patients with Crohns disease. When patients fail to respond to conservative therapy or severe narrowing of the duodenum develops, operation is required. The recent literature is limited in description of surgical treatment of such patients. We reviewed our experience with surgical management and outcomes in patients with DCD, including outcomes of laparoscopic bypass procedures.nnnSTUDY DESIGNnA retrospective review was undertaken of all patients who underwent surgical intervention for DCD between 1995 and 2006. Data collected included demographics, clinical presentation, operative and hospital course, and postoperative followup.nnnRESULTSnThirty patients had surgical intervention for DCD during the selected period. Four patients had duodenoenteric fistulas, resulting from complications of their disease in the distal gastrointestinal tract. Operations done for intrinsic DCD were: open bypass (n = 11), laparoscopic bypass (n = 13), and stricturoplasty (n = 2). Only one vagotomy was done. Mean followup was 58 months (range 6 to 144 months). Patients resumed oral diet 3.0 days after laparoscopic bypass, with mean discharge of 6.9 days, as compared with 4.4 days and 12.2 days after open bypass, respectively. In the early postoperative period (0 to 30 days), six major complications (n=5, 19%): persistent obstruction, anastomotic leak, small bowel obstruction, anastomotic bleeding (two patients), and respiratory failure, developed in four patients in the open (36%) and one patient in the laparoscopic (8%) bypass group. There were two more complications during longterm followup, for an overall major morbidity rate of 27%. Two patients experienced recurrence requiring revision (one in the open group and one in the laparoscopic group). Gastroduodenal ulcers requiring operation did not develop in any of the patients.nnnCONCLUSIONSnSurgery is a viable and safe option for patients with intractable duodenal Crohns disease. The laparoscopic approach during a bypass procedure, as opposed to an open bypass, may result in faster recovery, less morbidity, and comparable recurrence rate. There is no role for vagotomy in bypass procedures.

Rectal cancer and inflammatory bowel disease: natural history and implications for radiation therapy

PURPOSEnThere exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with IBD and rectal cancer in order to determine the natural history of the disease as well as the effect and tolerance of pelvic irradiation.nnnMETHODS AND MATERIALSnA retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thirty-five patients had ulcerative colitis and 12 patients had Crohns disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients, stage III in 13 patients, and stage IV in 9 patients. Surgical resection was performed in 44 patients. In two of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent postoperative adjuvant therapy (12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 patient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months).nnnRESULTSnThe 5-year actuarial results revealed an overall survival (OS) of 42%, a disease-free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5-year rate of 86% for patients with Tis-T2 disease compared to 10% for patients with T3-T4 disease (p < 0.0001). The presence of lymph node metastases also resulted in a decrease in DFS with a 5-year rate of 67% for patients with NO disease compared to 0% for patients with N1-N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grade with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respectively (p = 0.03). The T and N stages showed a statistically significant effect on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopathologic grade of the tumor did not significantly affect pelvic control. An analysis of high-risk patients (30) with T3-T4 or N1-N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26%, and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving RT (14 patients) with a 5-year PC of 60% compared to a rate of 23% for those patients not irradiated (16 patients). Acute complications (grade 3 or >) were noted in three patients (20%) receiving pelvic irradiation +/- chemotherapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastrointestinal toxicity. Two patients (13%) developed small bowel obstruction at 2 and 4 months, respectively, postirradiation which were managed conservatively. There were no long-term complications in patients irradiated.nnnCONCLUSIONnTreatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patients appeared to have a poorer outcome. In light of this finding and the ability of these patients to tolerate chemotherapy and pelvic irradiation, aggressive adjuvant therapy should be given to IBD-associated rectal cancer patients with high-risk features.

Relationship of the Number of Crohn's Strictures and Strictureplasties to Postoperative Recurrence

BACKGROUNDnStrictureplasty is well established as a safe and effective surgical therapy for Crohns disease (CD). Yet, postoperative recurrence after strictureplasty remains a problem for CD patients, and associated risk factors are still uncertain. The goal of this study was to examine the relationship between recurrence and the number of strictures (NSX) and strictureplasties (NSXP).nnnSTUDY DESIGNnThe authors prospectively created database was used to retrospectively identify patients who had undergone strictureplasty between 1984 and 2004. Recurrence was defined as reoperation, and rates were compared based on the NSX and NSXP using Kaplan-Meier curves. Cox regression analyses were used to evaluate the relationship between both NSX and NSXP and recurrence after adjusting for potential confounders.nnnRESULTSnThere were 339 strictureplasties performed in 88 patients at initial operation. The 5-year reoperation rates were 14% for patients with <or=8 strictures compared with 31% for those with>8 strictures (p=0.01). Five-year reoperation rates were 14% for patients with <or=4 strictureplasties compared with 33% for those with>4 strictureplasties (p < 0.01). In multivariate regression of NSX and NSXP as continuous variables, both were independently associated with recurrence (p <or= 0.02), with a 7% increase in recurrence for each additional stricture and 23% increase in recurrence for each additional strictureplasty.nnnCONCLUSIONSnThese data suggest that both the NSX and NSXP are associated with CD recurrence and may be used as prognostic indicators for CD.

Is there clinical, epidemiological and molecular evidence for two forms of Crohn's disease?

Crohns disease is an idiopathic chronic panenteric intestinal inflammatory disease. Data concerning the pathogenesis of, and the immune responses occurring in, Crohns disease are often conflicting. Current therapy is empirical and either non-specifically immunosuppressive or surgically ablative in nature. Although controversial, Crohns disease may be thought of as having two different presentations, an aggressive fistulizing form and an indolent obstructive form. This is analogous to the tuberculoid and lepromatous manifestations of leprosy. If correct, this subclassification may provide key insights into the pathogenesis and differing host immune responses in Crohns disease and also allow the development of more rational therapies.

Bleeding diathesis in amyloidosis with renal insufficiency associated with Crohn's disease: response to desmopressin.

A 53-yr-old man with a 33-yr history of Crohns ileocolitis, complicated by arthritis and cologastric fistulization, was diagnosed with GI amyloidosis at the time of proctocolectomy. He had marked proteinuria (4.2 g/24 h) and moderate renal insufficiency (BUN of 35 mg/dl and serum creatinine of 2.5 mg/dl). During the operation, he had severe bleeding that required 11 U of blood. Postoperatively, desmopressin was administered, which resulted in a prompt cessation of bleeding. This case demonstrates the efficacy of desmopressin in reversing the bleeding diathesis in surgical patients with amyloidosis complicated by renal insufficiency.

Surgical Technique and Difficult Situations for Ulcerative Colitis from Adrian Greenstein

Surgery for ulcerative colitis and Crohn’s disease has benefitted immeasurably from the transition from open to laparoscopic surgery. While traditional open surgery often provides easy visualization of the mesentery in relation to the intestine with short operative times, its well-known disadvantages include wound complications such as infection, disruption, and hernias, as well as a larger incision, worse cosmesis, more postoperative pain, more blood loss, later return of bowel function, later oral intake, and longer hospital stay [1].