Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo.

The strategy of enzymatic degradation of amino acids to deprive malignant cells of important nutrients is an established component of induction therapy of acute lymphoblastic leukemia. Here we show that acute myeloid leukemia (AML) cells from most patients with AML are deficient in a critical enzyme required for arginine synthesis, argininosuccinate synthetase-1 (ASS1). Thus, these ASS1-deficient AML cells are dependent on importing extracellular arginine. We therefore investigated the effect of plasma arginine deprivation using pegylated arginine deiminase (ADI-PEG 20) against primary AMLs in a xenograft model and in vitro. ADI-PEG 20 alone induced responses in 19 of 38 AMLs in vitro and 3 of 6 AMLs in vivo, leading to caspase activation in sensitive AMLs. ADI-PEG 20-resistant AMLs showed higher relative expression of ASS1 than sensitive AMLs. This suggests that the resistant AMLs survive by producing arginine through this metabolic pathway and ASS1 expression could be used as a biomarker for response. Sensitive AMLs showed more avid uptake of arginine from the extracellular environment consistent with their auxotrophy for arginine. The combination of ADI-PEG 20 and cytarabine chemotherapy was more effective than either treatment alone resulting in responses in 6 of 6 AMLs tested in vivo. Our data show that arginine deprivation is a reasonable strategy in AML that paves the way for clinical trials.

Stage one endometrioid endometrial adenocarcinoma: is there a role of traditional hospital follow-up in the detection of cancer recurrence in women after treatment?

OBJECTIVE: To investigate the rate of asymptomatic recurrence of stage 1 endometrioid endometrial cancer and assess the role of routine hospital follow-up after treatment. METHODS: We performed a retrospective case-note review study of women who were diagnosed with stage 1 endometrioid endometrial adenocarcinoma at Queen's Hospital, Romford, between January 2008 and December 2016. RESULTS: We included 299 patients with a median follow-up period of 44.4 months. All the patients underwent total hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy was offered to the patients subsequent to discussions in the multidisciplinary team meeting in accordance with the risk stratification criteria. There was no significant correlation between the risk factors and disease recurrence. In total, 11 patients presented with recurrent disease with original staging: 1a, n=6/199; and 1b, n=5/100. Four patients presented with vaginal bleeding due to vault recurrence and one patient with abdominal pain due to pelvic mass. Locoregional recurrence was an incidental finding in two other patients. Four patients presented with symptomatic distant metastases to the lung (n=2), liver (n=1), and bone (n=1). No asymptomatic recurrences were identified on routine follow-ups, despite several hospital appointments and clinical examinations. The recurrence rate for patients with stage 1a and 1b, grade 1, and grade 2 disease was 3.53%, and that for patients with stage 1a, grade 1, and grade 2 disease was 2.7%. CONCLUSION: Routine clinical examinations have a low yield in finding recurrence in asymptomatic women and should be questioned for their value, considering the limited resources of the National Health Service (NHS). Larger studies are required to support a stratified follow-up, which will include telephone and patient-initiated follow-up.

Massive gastric dilatation leading to acute respiratory distress 1 year after a Nissen fundoplication.

Acute massive gastric dilatation (AMGD) is a recognised complication after Nissen fundoplication.1 A 63-year-old man recently presented to our emergency department in acute respiratory distress, acute abdominal pain and distension, having had an elective umbilical port incisional hernia repair a day prior. In the year preceding his presentation, the patient had undergone a laparoscopic paraoesophageal hiatus hernia repair and excision of sac, posterior cruropexy, dual mesh reinforcement of repair and 360° fundoplication, as a day case. In between these two events, the patient was asymptomatic, and had a free diet with no further medical or surgical intervention. We hereby present successful management and discuss implications of this exceptional yet potentially life-threatening complication.