Time trends in mortality of oesophageal cancer in Finland over 30 years.

INTRODUCTION: Oesophageal cancer survival is reported by epidemiological studies, but knowledge on survival trends regarding different histologies and operative treatment status is lacking. MATERIALS AND METHODS: Data from all patients diagnosed with oesophageal cancer in Finland in 1987-2016 was collected from national registries. 1-, 3- and 5-year survival rates were examined stratified by histology (adenocarcinoma (OAC) and squamous cell carcinoma (OSCC)) and treatment strategy (surgery, no surgery). Hazard ratios (HR) with 95% confidence intervals (CI) for death were provided by multivariable Cox regression, adjusted for confounders. RESULTS: Of the 9102 patients, 3140 had OAC (1074 [34%] oesophagectomies), and 3778 had OSCC (870 [23%] oesophagectomies). Men were overrepresented in both OAC (77%) and OSCC (55%). The proportion of oesophagectomies decreased in both histologies. From 1987 to 1991 to 2012-2016, 5-year survival increased from 11% to 22% in OAC and from 7% to 13% in OSCC. For patients undergoing oesophagectomy, the corresponding increases were from 20% to 49% in OAC and from 11% to 54% in OSCC, and non-operated patients from 5% to 8% and from 5% to 7%, respectively. Earlier calendar period, older age and comorbidity were associated with mortality in both histologies. Female sex was a protective factor for patients operated for OSCC (HR 1.56 (95% CI 1.33-1.83), men versus women). CONCLUSIONS: The prognosis of oesophageal cancer has improved in Finland over the last 30 years in both main histological types. The survival of patients undergoing oesophagectomy has drastically improved, while the prognosis of patients not undergoing surgery is slowly improving but remains poor.

Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. OBJECTIVE: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-ß (Aß) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. METHODS: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed Aß plaques in frontal cortical brain biopsy and 13 iNPH patients without Aß pathology. CSF Amyloid-ß42 (Aß42), total tau (T-tau), phosphorylated tau (P-tau181), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. RESULTS: All biomarkers but Aß42 increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. Aß42 instead showed divergent longitudinal decrease between Aß-positive and -negative patients in L-CSF, and thereafter increase in Aß-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (Aß42 R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (Aß42 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only Aß42 showed higher concentration in non-carriers of allele ɛ4. CONCLUSION: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy Aß pathology, while NFL normalized toward its pre-shunt levels. Aß42 as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V- than L-CSF yet showing strong correlations.

Procedural risk factors, incidence and timing of reintervention after treatment for native coarctation of the aorta in children: a population-based study†.

OBJECTIVES: The aim of the present study was to evaluate procedural risk factors, incidence and timing of reintervention because of recurrent aortic coarctation in children. METHODS: The study cohort consisted of 304 patients with isolated coarctation: 251 underwent surgery and 53 were treated percutaneously (40 balloon angioplasty, 13 stent) at the Helsinki Children's Hospital in 2000-2012. Characteristics, intervention and reintervention data were retrospectively collected from clinical records until 2014 (median follow-up 7.9 years). Age- and sex-matched comparisons between the treatment groups were performed in 86 patients (surgery n = 43, percutaneous n = 43). RESULTS: Forty of the 251 (16%) patients after surgery, 9/40 (23%) patients after balloon angioplasty and 4/13 (31%) patients after stent placement underwent a reintervention after a median time of 3.4, 11.7 and 19.5 months (P < 0.05), respectively. In the surgery group, all reinterventions occurred in children operated on ≤12 months of age and were related to lower body weight and smaller dimensions of the aorta. In the balloon angioplasty group, a higher post-procedure systolic arm-leg blood pressure gradient was associated with reintervention. After stent placement, three-fourths of the reinterventions were performed in a planned postinterventional catheterization. In the age- and sex-matched comparisons (median 5,7 years, range 0,5-17,6), post-procedure blood pressure gradients were higher (mean 10 vs 4 mmHg, P = 0.03), and reinterventions were more common (28%, 95% confidence interval 17-43 vs 2%, 95% confidence interval 0-12) in the percutaneous group compared to the surgery group. CONCLUSIONS: Reinterventions after surgery in neonates were relatively common. In older children, percutaneous treatment carried a higher risk of reinterventions, which were mainly related to residual coarctation after primary treatment.

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH.

OBJECTIVE: To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. METHODS: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. RESULTS: The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. CONCLUSIONS: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.

Incomplete protection of genetic integrity of mature spermatozoa against oxidative stress.

Although DNA damage in human spermatozoa is associated with adverse health effects, its origin is not fully understood. Therefore, we assessed biomarkers in ejaculates that retrospectively reflect processes that occurred in the epididymis or testis. Smoking increased the amount of DNA strand breaks (P<0.01), and enhanced the presence of vitamin C radicals in seminal plasma. In vitro, vitamin C protected mature spermatozoa against DNA damage, but this protection appeared to be insufficient in vivo. CAT and DDIT4 expression in spermatozoa were higher in smokers than in nonsmokers, but were not related to DNA damage. CAT and DDIT4 expression were inversely related with sperm count (P=0.039 and 0.024 resp.), but no effect was observed for SOD2 expression. These data indicate that spermatozoa of smokers encounter higher levels of oxidative stress. Expression of antioxidant enzymes and seminal vitamin C were insufficient to provide full protection of spermatozoa against DNA damage.

[Maldigestion during chronic pancreatitis]. / Maldigestion au cours des pancréatites chroniques.

During chronic pancreatitis exocrine pancreatic insufficiency develops leading to a loss of pancreatic enzymes in the duodenum, especially pancreatic lipase. As a result, lipid maldigestion occurs (on a clinical standpoint it is more serious than proteic maldigestion) responsible for greasy diarrhoea with steatorrhoea and abdominal discomfort. Stearorrhoea is diagnosed thanks to a direct measurement of the total lipid content in the stool rather than indirect test. The pancreatic origin of the steatorrhoea is demonstrated in view of the clinical history of the disease, the normal duodenal biopsy specimen or by imaging or biological testing. Steatorrhoea is treated by pancreatic extract given as a form of enteric coated microcapsules (which are protected from proteolitic and acidic digestion) together with some dietary advises.

[Lanreotide acetate may cure cystic dystrophy in heterotopic pancreas of the duodenal wall]. / Le lanréotide peut traiter une dystrophie kystique de la paroi duodénale développée sur pancréas aberrant.

Cystic dystrophy in heterotopic pancreas of the duodenal wall is a rare but benign disease, associated in most of the cases with chronic pancreatitis. Treatment of this disease is controversial. We report here the use of a long-acting somatostatin synthetic stable analogue in the treatment of a cystic dystrophy in heterotopic pancreas of the duodenal wall: a 45-year-old man, hard drinker, was treated successfully during three months with lanreotide acetate; disappearance of cysts was confirmed by a computed tomography two months after the end of treatment.

[Adenocarcinomas of the distal esophagus and gastric cardia: what chemotherapy or chemoradiotherapy for recurrent or metastatic disease?]. / Adénocarcinomes du bas oesophage et du cardia: quelle chimiothérapie ou chimioradiothérapie dans le traitement des récidives et des métastases?

Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dyphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs).

Endorectal sonography in the evaluation of rectal and perirectal disease.

Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases.