Likely impeding a wider recognition of the disease process earlier was the inability to precisely define the pathophysiology or epidemiology. Leading opinions of the 1930s were a yet undetermined microbiologic pathogen (bacterial, toxin-mediated, viral, protozoa), fecal stagnation due to the ileocecal valve, foreign body reaction, lymphangitis, vascular insult, or hereditary. Early case series speculated that there was a link to Jewish ancestry as hospitals with large Jewish populations were amongst the first to report cases. Genetic associations were first sug-gested by noting familial clustering as early as the 1930s and were confirmed decades later by identifying common polymorphisms (i.e., NOD2, ATG16L1) that affect host- microbe interactions in the intestinal tract and autophagy, respectively. Many more genetic associations have been since described.

The early surgical treatment of Crohn’s disease was surrounded by controversy given the difficulty in diagnosis and the unknown prognosis. Initial case series reported that patients frequently underwent appendectomy when in retrospect the clinical picture and gross operative findings were more consistent with acute ileitis.
With improved recognition of the disease, controversy existed as to the best operative strategy.

Resection was mandated by some groups, while others advocated for surgical bypass of the affected bowel. In groups advocating resection, further debate existed as to the merits of a single or multi-stage operations which included a first stage bypass followed by delayed resection of abnormal bowel. At the Mount Sinai Hospital,  Dr.  Berg initially advocated for right colectomy as performed for cancer but later changed his preference to bypass owing to lower surgical mortality rates. The bypass procedure was adopted as the procedure of choice at The Mount Sinai Hospital and was initially planned as a part of a staged operation and not definitive therapy .  However,  clinical improvement following bypass alone resulted in its being adopted as sole surgical therapy.

Principles touted by Ginzburg, in a 1942 review of cases at The Mount Sinai Hospital, included the need to evaluate the entire small bowel for skip lesions and that ileotransverse colostomy with exclusion should be the definitive surgical procedure, as he found a 0 % mortality rate when this procedure was performed .  Diffuse involvement of the small bowel was widely considered to be a contraindication to surgery because of the significant risk of short bowel syndrome. Improvement in surgical mortality in successive decades likely had more to do with improvements in anesthesia and perioperative care rather than choice of procedure.

One particularly historic case of Crohn’s disease involved the 34th President of the United States, Dwight David Eisenhower. His illness and treatment were subsequently reported in detail by Lt. Gen. Leonard Heaton et al.. In 1956, at 65 years of age,  President Eisenhower presented with vague lower abdominal discomfort. Symptoms progressed to include obstipation, abdominal distention,  and bilious emesis.  After initial fluid resuscitation, he was brought to Walter Reed Army Hospital. He had a history of prior appendectomy and was known to have suffered from bouts of recurrent abdominal pain (Fig.  1.5 ). 

On June 9th, he underwent laparotomy via a right paramedian incision.  Gross description of the findings depicted a long strictured segment of terminal ileum with “claw-like”  projections of mesenteric fat towards the antimesenteric border and no identifiable skip lesions.  Ileotransverse colostomy was performed.  His post-operative course was notable for passage of flatus on POD#5 and full resumption of administrative duties.  He was ultimately discharged on post-operative day 21. There was significant criticism of the choice of operation at the time, since it did not involve resection.  The surgeons concluded that a bypass was the most expeditious conservative operation given the President’s preoperative state and his recent myocardial infarction.

During the 1950s, increasing experience lead clinicians to recognize that despite surgery, the disease process resulted in high recurrence rates.  Large retrospective series from the major teaching institutions in the 1950s became available,  and further scrutiny of the optimal operative strategy developed .  These series allowed direct comparisons of patients who underwent the two predominating operations of the time:  resection versus bypass.

Endpoints such as disease persistence and clinical recurrence were compared directly and were shown to favor resection with primary anastomosis (Fig.  1.6 ). Soon, additional concerns about the bypass procedure developed. Greenstein et al. from The Mount Sinai Hospital in the 1970s, published reports of carcinoma in the excluded bowel segment. 

With high rates of surgical recurrence prevalent,  even when all macroscopic disease was resected, there was significant controversy over the necessity of disease free margins. The effect of residual microscopic disease at the resection margins was evaluated for both recurrence risk and its potential for post-operative complication (e.g.,  anastomotic dehiscence).  Retrospective reviews showed positive microscopic margins in up to 50 % of resections; however, no statistically significant effect was found on the rate of anastomotic complications .  Early retrospective reviews suggested that the risk of recurrence was unaffected by presence of microscopic disease at the surgical margin. A randomized trial by Fazio et al., at the Cleveland Clinic, in 1996 concluded that recurrence rates did not differ when extended resection was performed even when microscopic disease was present at the margin. This provided further support to the practice of limiting extent of bowel resection in order to preserve as much intestinal length and absorptive surface as possible.

The presence of proximal small bowel lesions was considerably troublesome,  and was widely considered a contraindication to surgery, as reiterated by Crohn in the 1950s .  Common practice, when small bowel strictures were symptomatic, was either to avoid surgery with supportive care alone, perform limited resections or to bypass involved proximal segments of bowel.