Intestinal Malrotation Associated With Invagination of the Distal Ileum and Cancer of the Cecum: A Case Report and Literature Review

Associated midgut malrotation and colon cancer in adult patients is extremely rare and associated with delayed diagnosis and increased morbidity. We present the case of a patient with a three-week history of weakness, diarrhea, and abdominal pain with invagination of the distal ileum. Exploratory laparotomy with ileocecal resection revealed invagination, malrotation, and cecal adenocarcinoma.


Introduction
Intestinal malrotation is an in-utero developmental disorder, characterized by an improper fixation of the midgut and failure of its normal embryonic rotation between the fifth and 12th week of gestation [1]. This anomaly is estimated to occur in around one in 500-6,000 newborns and presents within the first month of life in 64-80% of the patients [2]. Although most of the cases of intestinal malrotation are recognized as a cause of intestinal obstruction in newborns, its clinical manifestation in adults can be variable and can include nausea, vomiting, dyspepsia, diarrhea, chronic abdominal pain, intestinal obstruction, and volvulus [2][3][4][5][6][7][8][9][10][11][12][13]. Concomitant midgut malrotation and colon cancer is very rare. We report a case of open hemicolectomy for cecum cancer in a patient with intestinal malrotation and review the literature on this topic.

Case Presentation
An 86-year-old woman with Alzheimer's disease was admitted to our emergency department after an approximately three-week history of weakness, diarrhea, and abdominal pain. She had a medical history of open appendectomy in adolescence, endoscopic colonic polypectomy, and no previous abdominal pain. Malrotation was not known beforehand. A physical examination revealed conspicuous abdominal tenderness and abdominal distension. No lump was palpable. Laboratory values showed an elevated C-reactive protein (93 mg/L), normal lactate, and anemia (67 g/L) requiring blood transfusion. Abdominal computed tomography (CT) with intravenous contrast ( Figure 1) showed a thickened ascending colon with invagination of the distal ileum, as well as imaging features suspicious for sigmoid volvulus. Due to the extensive invagination, an exploratory laparotomy was deemed necessary. Intraoperative examination revealed that the thickened terminal ileum was invaginated into the cecum and reached up to the right colonic flexure. During surgery, we found non-rotation of the intestine: the mobile cecum was located in the midline, but the descending colon was attached to the retroperitoneum, and the small intestine occupied the right side of the abdomen. The distal ileum was carefully and manually released from the colon without any visible serosal lesions. The entry point of invagination appeared to be in the area of the former appendectomy site. Due to the cecal induration at the entry point of the distal ileum, we performed a 7 cm long ileo-cecal resection, with lymph node dissection and ileo-ascending end-to-end anastomosis. Surprisingly, histopathological examination revealed moderately differentiated adenocarcinoma of the cecum (pT4a pN0 (0/14) M0 L0 V0 Pn0 G2), with carcinoma-free resection borders. Postoperatively, the patient was treated with intravenous antibiotics (ciprofloxacin and metronidazole) for 48 hours. We discussed the recommendation for oncological resection (right hemicolectomy) and adjuvant chemotherapy with the patient's family. Due to the patient's age, comorbidities, and general condition, the patient underwent no further surgery or chemotherapy. No adverse events or surgical complications were observed during the postoperative course, and the patient was discharged on postoperative day eight.

Discussion
Intestinal malrotation is a congenital abnormality resulting from a less-than-normal 270° anti-clockwise rotation of the midgut along its vascular pedicle during embryologic development. More than 90% of patients with intestinal malrotation present symptomatically within the first year of life, although malrotation can remain asymptomatic even in adults [10,13].
There are three types of malrotation depending on when the normal growth of middle intestine is interrupted: (1) non-rotation (type IA): when the first 90° anti-clockwise rotation occurs; (2) incomplete intestinal rotation (type II): several abnormalities due to variations in anti-clockwise rotation of the last 180°o f the intestine; (3) inverse rotation (type III): when the postarterial section of the midgut first re-enters the abdominal cavity. Non-rotation is the most frequent type of reviewed cases and has been confirmed in 10 patients. The present case also showed findings of non-rotation type, which includes left positioned cecum and ascending colon with right-sided duodenojejunal junction. The development of imaging technology has increased the diagnosis rate of intestinal malrotation. Nowadays, CT is one of the most useful diagnostic examination for intestinal malrotation in adults. On the other hand, many cases of malrotation are still incidentally revealed by operation for concomitant disease, and as in our case, as well as most of the case reports which we reviewed, the intestinal malrotation was discovered only when laparoscopy or laparotomy was carried out. In our literature review, we identified 13 other cases of intestinal malrotation and colon cancer. However, most of the patients identified in our review ( Table 1) had symptoms such as chronic abdominal pain, diarrhea or constipation, fatigue, anemia, among others. Table 1 summarizes the cases of colon cancer in patients with intestinal malrotation that are reported in the English literature [2][3][4][5][6][7][8][9][10][11][12][13]. Most of the case reports indicate cecum cancer (46.2%); ascending colon cancer (30.8%); and transverse colon, descending colon, and sigmoid colon cancer (7.7%) each. The tumor location is mostly diagnosed by colonoscopy. Although there is no direct evidence for the connection between a congenital anomaly and carcinogenesis, Ren and Lu [4] described that intestinal malrotation may cause chronic bowel obstruction resulting in inflammation and colon cancer development. With respect to the surgical approach, in our reviewed reports, open surgery was performed in 53.8% of the cases, laparoscopy in 38.5% of the cases, and one patient (7.7%) underwent conversion to open laparotomy. Laparoscopic surgery for colon cancer is becoming more popular and advanced. On the other hand, intestinal malrotation is associated with vascular abnormality, and it is difficult to safely perform laparoscopic hemicolectomy and lymphadenectomy for patients with this condition. In our case, we preferred laparotomy: first, because of extensive distal ileum invagination into the ascending colon. Second, the presence of ambiguous abdominal CT findings led us to consider laparotomy to be more safe and reliable.

Conclusions
We report the case of a patient with cecum cancer who also had intestinal malrotation and distal ileum invagination. Open surgical resection and lymphadenectomy were performed. Anatomical malrotations can lead to challenging approaches for surgical resection. For safety, surgeons should always consider a laparotomy if malrotation is suspected on imaging beforehand. The causal relationship between intestinal malformation and carcinogenesis is not clearly established and remains to be further investigated.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other