Clinical Case Summary

A 56-year-old woman was referred to tertial hospital for decompensated liver cirrhosis of unknown origin. She was slightly overweight (BMI 25.3) and denied alcohol consumption or any history of liver disease. Since childhood, she had been diagnosed with congenital ichthyosis, strabismus, and myopia, had a history of bilateral neurosensory hearing loss, arterial hypertension, and cataracts. Since 2016, she had been experiencing progressive muscle weakness, and intermittent speech impairment. The patient complained of eyes dryness, episodic joint and muscle pain, muscle weakness, general malaise, dizziness, dry and scaling skin. Physical examination revealed diffuse skin dryness, scaling and an enlarged abdomen. Radiological examination revealed a cirrhotic liver, splenomegaly and moderate ascites. The MELD score was 18 and the Child-Pugh - 9. Laboratory tests excluded Wilson's disease, autoimmune liver diseases, hemochromatosis, α-1 antitrypsin deficiency. Liver biopsy showed macro and microvesicular steatosis (>50% of hepatocytes with lipid vacuoles), hepatocytes ballooning and inflammation compatible with MAFLD related liver cirrhosis. In peripheral blood smear was detected multiple lipid vacuoles in the leukocytes cytoplasm, known as Jordan‘s anomaly, confirming Chanarin–Dorfman syndrome (CDS) - a rare autosomal recessive neutral lipid storage disease. Genetic testing confirm diagnosis and revealed a potentially pathogenic homozygous c.133+3A>C mutation in the ABHD5 gene. Due to progression of liver failure patient was referred for liver transplantation (LT) and liver was successfully transplanted in 2024.
The case showed that LT is a realistic option if liver function deteriorates in CDS. LT does not affect neurological, dermatological and other extrahepatic symptoms of the syndrome. In early post-transplant period attention should be paid to possible temporary worsening of heart failure due to cardiomyopathy associated with CDS.

Introduction

In contrast to mucosal T1 rectal cancers with an R0 rate of up to 92% at centers, R0 resection may drop to 30% in case of deep sm infiltration due to thermal artefacts at the basal resection margin. TME often follows as completion surgery. Deep sm infiltration as isolated risk factor excluding L+, V+, G3 and Bd2-3 seems associated with a low risk of LN metastases of only 2.6%. Endoscopic Intermuscular Dissection (EID) is a new flexible endoscopic dissection technique with separation of the circumferential and longitudinal muscular layer. EID ideally provides a specimen incl. the entire submucosa and inner circumferential mp layer. 12 sequential EIDs were compared to 53 historical rectal ESDs with HGIEN or rectal cancer as hp. result.

Aims & Methods

Lesions with biopsy proven ADC or HGIEN of the rectum without endoscopic, EUS or clinical signs of deep local infiltration. 2 pat. included after neo-adjuvant RT/Ch th. 24 and 26 mo before with complete response and refusing definitive surgery. Both with local flat polyps (SSA (1) hyperplastic polyp / LGIEN adenoma (2). Endoscopy, EUS, MRI, CT and rectal digital examination without suspicion of local malignant infiltration. Pts were offered to prospectively undergo EID after extensive informed consent within a prospective protocol. All procedures were carried out under gen. anesthesia by an exp. interv. endoscopist with >1000 ESDs. Results of EID were compared to a historical collective of 53 cases with rectal ESD and a histological result of rectal cancer or HGIEN (08-2018 to 12-2021).

Results

From 11-2023 to 09-2024, 12 EIDs were carried out in 12 pts (6 f/ 6 m; mean 63 y; 34-83y). 09/12 lower rectum, 1/12 middle, 1/12 lower and middle, 1/12 upper rectum. 'En bloc' resection rate was 100%, R0 resection rate 89% for neoplasia / HGIEN. Histopathology: 3x ADC G2, 6x HGIEN, 3x LGIEN including both cases with neodajuvant RT/Ch. R0 resection was achieved in 2 of the 3 ADCs. Both with deep sm infiltration without any other risk factors. Tumor board: close clin. & imaging FU. In the 3rd ADC: TU infiltration of inner muscular layer (T2). Pat. underwent uneventful TME 10 d after EID. Clinical FU in all others. Length of hosp. stay 7.1 days. No serious major complications. All pts. closely followed with uneventful FU.
In the historical ESD group R0 resection was achieved in 100% of the HGIEN cases (45/45) but only in 3/8 lesions (37.5%) of cases with adenocarcinoma.

Conclusion

EID seems a new perspective for the endosc. resection of T1 rectal cancers and suspicious polyps in the rectum. More experience and a comparison to surgical local procedures (TAMIS etc.) is necessary for the final assessment of EID as new promising endoscopic technique.

References

Introduction

Chronic intestinal pseudo-obstruction (CIPO) is a rare, heterogeneous, and challenging gastrointestinal motility disorder lacking clinical guidelines in adults.

Aims & Methods

We aimed to develop an international consensus among international experts in gut motility on the diagnosis and management of CIPO based on existing literature and expert opinion. Two experts from each continental motility society and experts on pathology, surgery, and nutritional aspects of CIPO were selected for participation. A list of >130 statements was drafted, subdivided into 11 topics. After revisions and validation by the experts of the list of statements, a systematic literature review was performed to summarize available data on every statement. Using a Delphi process of 3 voting rounds, consensus statements were identified (defined as >80% agreement).

Results

Consensus was reached for 77/139 statements. The panel defined CIPO as symptoms caused by severe small bowel dysmotility without mechanical obstruction, and with documented dilated intestine or air/fluid levels, mimicking mechanical obstruction. Pseudo-obstructive episodes or continuous pseudo-obstructive symptoms were considered a cardinal feature of CIPO. Abdominal pain, bloating, and distension were also considered cardinal symptoms, while nausea/vomiting, diarrhea, or constipation were considered associated symptoms.
Radiographic imaging was considered mandatory in the diagnostic work-up, to confirm intestinal dilation or air/fluid levels and to rule out mechanical obstruction.. No other diagnostic test was considered indispensable for the diagnosis, including endoscopy, manometry, or laparoscopy. Screening for secondary causes of CIPO, including systemic sclerosis, paraneoplastic disease, or infectious disease, was supported, with a possible role for transmural histology. Differential diagnoses, including drug adverse effects, adhesions, or enteric radiation, should be ruled out. The experts also recommended screening for complications such as nutritional deficiencies and osteoporosis.
Management requires dietary adjustment, with supplementation for deficiencies, and setting up home parenteral nutrition if enteral nutrition fails. Small intestinal bacterial overgrowth was recognized as a main contributor to symptom aggravation and should be treated by intermittent antibiotics without the need for breath testing confirmation in patients with CIPO. There was no consensus regarding choice or efficacy of drug therapy, including prokinetics (e.g. pyridostigmine, prucalopride), laxatives, or somatostatin analogs. Opioids and surgical resections should be avoided; although endoscopic or surgical decompression procedures may be helpful in acute or persisting pseudo-obstructive symptoms.

Conclusion

This expert consensus developed key statements for the definition, diagnosis, and treatment of CIPO in adult patients. It provides the opportunity to harmonize the management of these patients and to highlight the gaps in the current literature.

Disclosure

Jan Tack has given Scientific advice to Aclipse, Adare, AlfaSigma, Clasado, Danone, Falk, FitForMe, Ironwood, Kyowa Kirin, Menarini, Promed, Ricordati, Takeda, Truvion, Tsumura, Zealand Pharmaceuticals, has received research support from Biohit, Kiowa Kirin, ProMed, Sofar and Takeda, and has served on the Speaker bureau for Abbott, Bio-Codex, Mayoly, Menarini, ProMed, Reckitt-Benckiser, Schwabe, Takeda, Thai Meiji and Truvion Pharmaceuticals.