Differences in Pathology and Mutation Status Among Colorectal Cancer Patients Younger Than, Older Than, and of Screening Age.

BACKGROUND: Screening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages. PATIENTS AND METHODS: We retrospectively analyzed tumors from stage IV colorectal cancer patients from a central pathology laboratory in Brazil that is a reference for mutational profiling countrywide. Patients were classified into age groups as follows: prescreening age (PrSA; < 45 years old), screening age (SA; 45-75 years old), and postscreening age (PoSA; > 75 years old). Every tumor was centrally reviewed by the pathologist. Groups were compared regarding clinicopathologic features, and the presence of RAS (renin-angiotensin system) and BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations. RESULTS: We included 1635 patients (215 PrSA, 1213 SA, 207 PoSA). There was no difference among groups regarding sidedness (P = .65) and KRAS (Kirsten rat sarcoma viral oncogene) mutations (P = .57). Stage IV disease at diagnosis (P = .04), the presence of a signet-ring cell component (P < .001), and poorly differentiated tumors (P = .02) were most common in young patients, while BRAF and NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog) mutations were significantly more common among PoSA patients (P = .002 and .03, respectively). When divided by age decade, KRAS mutations seem to have a stable frequency among all ages, while the BRAF mutation rate increased with increasing age. CONCLUSION: BRAF mutations are more frequent among PoSA patients, and this seems to be a continuous trend. PrSA and PoSA patients seem to present a distinct profile from SA, including differences in molecular and pathologic aspects. These findings could impact the frequency of screening tests among different age groups.

Functional pancreatic neuroendocrine tumour causing Cushing's syndrome: the effect of chemotherapy on clinical symptoms.

BACKGROUND: Neuroendocrine tumours (NETs) are a heterogeneous group of diseases that can originate from any part of the gastrointestinal tract, bronchi, thyroid and pancreas. These tumours may be functioning or not depending on their ability to produce active substances, such as adrenocorticotrophic hormone (ACTH). ACTH-producing pancreatic neuroendocrine tumours are rare, with limited data about effective antitumor therapies. CASE REPORT: A 58-year-old man with a history of type-2 diabetes mellitus and arterial hypertension was diagnosed with Cushing's syndrome (CS) secondary to an ACTH ectopic production from a well-differentiated neuroendocrine tumour of the pancreas metastatic to the liver. The patient underwent initial body-caudal pancreatectomy, splenectomy and hepatic nodulectomy with subsequent recurrence. Hepatic embolisation and somatostatin analogues were used to control CS but without success. Bilateral adrenalectomy led to CS control, while capecitabine and oxaliplatin (CAPOX) was effective in controlling tumour growth and ACTH production. DISCUSSION: ACTH-producing pancreatic neuroendocrine tumours are rare, aggressive and difficult to treat with available therapies. In settings of limited resources, such as in developing countries where targeted therapies are not available, cytotoxic chemotherapy with CAPOX represents a good and inexpensive option to control ACTH-producing pancreatic neuroendocrine tumours. Because of its complexity, the management of this tumour should be performed by multidisciplinary teams.

Refractory hypoglycemia in a patient with functional adrenal cortical carcinoma.

Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH-IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180-780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267-616 ng/mL) and an elevated IGF-II/IGF-I ratio (21.9; reference: ~3). CT scan revealed a large expansive mass in the right adrenal gland and pulmonary and liver metastases. During hospitalization, the patient experienced frequent difficult-to-control hypoglycemia and hypokalemia episodes. Octreotide was ineffective in controlling hypoglycemia. Due to unresectability, chemotherapy was tried, but after 3 months, the patient's condition worsened and progressed to death. In conclusion, our patient presented with a functional adrenal cortical carcinoma, with hyperandrogenism associated with hypoinsulinemic hypoglycemia and blockage of the GH-IGF-I axis. Patient's data suggested a diagnosis of hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor (low levels of GH, greatly decreased IGF-I, slightly decreased IGF-II and an elevated IGF-II/IGF-I ratio). LEARNING POINTS: Hypoglycemyndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by adrenal tumors is a rare condition.Hypoinsulinemic hypoglycemia associated with hyperandrogenism and blockage of the GH-IGF-I axis suggests hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor.Hypoglycemia in cases of NICTH should be treated with glucocorticoids, glucagon, somatostatin analogs and hGH.