Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance

Hereditary diffuse gastric cancer (HDGC) is a relatively rare disorder, with a mutated CDH1 gene as the only known cause. Carriers of a germline mutation in CDH1 have a lifetime risk of >80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting early stages of HDGC, prophylactic gastrectomy is advised for this patient group. Little is known about other types of familial gastric cancer. The Dutch working group on hereditary gastric cancer has formulated guidelines for various aspects of medical management for families and individuals at high risk of developing gastric cancer, including criteria for referral, classification, diagnostics, and periodic gastric surveillance. These guidelines are not limited to HDGC and are therefore partially complementary to the guidelines on hereditary diffuse gastric cancer of the international gastric cancer linkage consortium (IGCLC 2010). In order to optimize the care and increase the knowledge on hereditary gastric cancer it is important to centralize medical care for these patients. National and international collaboration is warranted to improve the quality of research by increasing the size of study cohorts.     

Papilledema in patients with Apert, Crouzon, and Pfeiffer syndrome: prevalence, efficacy of treatment, and risk factors

Patients with syndromic craniosynostosis are at risk for elevated intracranial pressure because of various physiologic and anatomic abnormalities. The aims of this study were to determine the prevalence of papilledema in syndromic craniosynostosis, to evaluate the results of the treatment, and to examine the risk factors.This is a retrospective study on 84 patients with Apert, Crouzon, or Pfeiffer syndrome. Papilledema was defined as blurring of the margins of the optic disk. The association between clinical symptoms, beaten-copper pattern on skull radiograph, ventricular dilatation on computed tomography scan, and papilledema was assessed.Papilledema was present in 51% of the patients. No relation between specific clinical symptoms and papilledema was found. The significant associations were complex craniosynostosis, exorbitism, and ventricular dilatation.The prevalence of papilledema in patients with Apert, Crouzon, or Pfeiffer syndrome is high, not only before cranial decompression but also after vault expansion. Annual fundoscopy is recommended to screen for papilledema. We consider that early decompressive surgery (within the first year of age) prevents the development of papilledema and, most likely, elevated intracranial pressure.     

CDKN2A(p16) and HRAS are frequently mutated in vulvar squamous cell carcinoma

Background

Two etiologic pathways of vulvar cancer are known, a human papillomavirus (HPV)- and a TP53-associated route, respectively, but other genetic changes may also play a role. Studies on somatic mutations in vulvar cancer other than TP53 are limited in number and size. In this study, we investigated the prevalence of genetic mutations in 107 vulvar squamous cell carcinomas (VSCCs).

Methods

A total of 107 paraffin-embedded tissue samples of primarily surgically treated VSCCs were tested for HPV infection and screened for mutations in 14 genes (BRAF, CDKN2A(p16), CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53) using Sanger sequencing and mass spectrometry.

Results

Mutations were detected in 7 genes. Of 107 VSCCs, 66 tumors (62%) contained at least one mutation (TP53 = 58, CDKN2A(p16) = 14, HRAS = 10, PIK3CA = 7, PPP2R1A = 3, KRAS = 1, PTEN = 1). Mutations occurred most frequently in HPV-negative samples. Five-year survival was significantly worse for patients with a mutation (47% vs 59%, P = .035), with a large effect from patients carrying HRAS-mutations.

Conclusion

Somatic mutations were detected in 62% of VSCCs. As expected, HPV infection and TP53-mutations play a key role in the development of VSCC, but CDKN2A(p16), HRAS, and PIK3CA-mutations were also frequently seen in HPV-negative patients. Patients with somatic mutations, especially HRAS-mutations, have a significantly worse prognosis than patients lacking these changes, which could be of importance for the development of targeted therapy.     

The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

Objective

To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type.

Influence of sleep on symptom improvement and return to work in clinical burnout

OBJECTIVES: The current study examined the extent to which symptom improvement and full return to work occurs among clinically burnt-out employees and what the influence of concurring sleep problems is with respect to health recovery. METHODS: Fifty-nine burnt-out employees on extended sick leave assessed their symptoms for 2 weeks using an electronic diary. After 6 months, the measurements were repeated. Symptom levels were compared with those of a healthy reference group that was assessed only once. RESULTS: After 6 months, all burnout symptoms had decreased significantly, and full return to work was achieved by 37% of the burnt-out individuals. The symptom levels at 6 months of follow-up among those who had fully returned to work were similar to healthy levels and significantly lower than the levels of those still on sick leave. The persons who benefited poorly from sleep at baseline had higher exhaustion levels at follow-up than those who benefited from sleep. Trouble falling asleep and less refreshing sleep at baseline hampered eventual full work resumption. CONCLUSIONS: The results show that a significant number of clinically burnt-out employees is able to recover in a 6-month period and that sleep plays an important role both in symptom improvement and in return to work.     

Structured game-related group therapy for an adolescent with Acquired Brain Injury: a case report

The use of Interactive Computer Play (ICP) in rehabilitation is developing rapidly and is especially promising in interdisciplinary pediatric rehabilitation. This case report examines how the Nintendo Wii? can be used in the rehabilitation of an adolescent with Acquired Brain Injury (ABI). In particular it describes the use of the Nintendo Wii in a structured group therapy called the GameLaB.