A novel approach to paraneoplastic intestinal pseudo-obstruction.

Paraneoplastic neurologic syndromes (PNS) are uncommon, affecting fewer than 1 in 10,000 patients with cancer. PNS, while rare, can cause significant morbidity and impose enormous socio-economic costs, besides severely affecting quality of life. PNS can involve any part of the nervous system and can present as limbic encephalitis, subacute cerebellar ataxias, opsoclonus-myoclonus, retinopathies, chronic intestinal pseudo-obstruction (CIPO), sensory neuronopathy, Lambert-Eaton myasthenic syndrome, stiff-person syndrome, and encephalomyelitis. The standard of care for CIPO includes the use of promotility and anti-secretory agents and the resection of the non-functioning gut segment; all of which can cause significant compromise in the quality of life. There is significant evidence that paraneoplastic neurologic syndromes are associated with antibodies directed against certain nerve antigens. We successfully treated a patient with CIPO in the setting of small cell lung cancer with a combination of rituximab and cyclophosphamide. The patient, who had failed to respond to prokinetic agents, anti-secretory therapy, and multiple resections, responded to the immunomodulatory therapy, with minimal residuals with PEG tube feeding and sustained ostomy output. The use of rituximab and cyclophosphamide should therefore be considered in patients with CIPO, especially if it can avoid complicated surgical procedures.

Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer.

BACKGROUND: The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II-III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. METHODS: Stage II-III colorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between 2002 and 2006 were identified. Computerizedt omography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length x width x height of the spleen). RESULTS: 40 patients were identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. CONCLUSIONS: Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy.

Malignant gastroparesis: pathogenesis and management of an underrecognized disorder.

Gastroparesis is a disorder of the stomach caused by delayed gastric emptying in the absence of mechanical obstruction. Symptoms of gastroparesis include nausea, vomiting, early satiety, bloating, and abdominal discomfort. Gastroparesis has been described as a complication of several malignancies, including gastric, pancreatic, gallbladder, esophageal, and lung cancers, as well as leiomyosarcoma. The prevalence of malignant gastroparesis (MG) is unknown, and this entity is widely underrecognized and undertreated. Diabetes mellitus is the most common identifiable cause of benign gastroparesis, ie, gastroparesis occurring in the absence of an underlying malignant pathology. In the setting of malignancy, gastroparesis may result from the cancer itself or may be a complication of its treatment with such modalities as surgery, radiation therapy, or chemotherapy. Coexisting conditions, including diabetes, hypothyroidism, and neurologic diseases, may further exacerbate MG. The pathogenesis of MG is not clearly understood at present. However, mechanisms suggested in the literature include postvagotomy syndrome, malignant infiltration of the autonomic nervous system, and paraneoplastic dysmotility with autoantibody-mediated destruction of the enteric nervous system (the interstitial cells of Cajal, also called the intrinsic pacemaker of the gastrointestinal tract, or the myenteric plexus). Appropriate treatment of MG may help to avoid serious consequences, such as cancer cachexia, intolerance of oral anticancer agents, dehydration, and hospitalization. In this article, we will describe our institutional experience with MG and will provide a concise review of the literature. Guidelines for management will be suggested.