A prognostic systemic inflammation score (SIS) in patients with advanced intrahepatic cholangiocarcinoma.

PURPOSE: Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. METHODS: SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan-Meier analyses, and Cox proportional models. RESULTS: Median overall survival (OS) of the entire cohort was 14.8 months (95% CI 11.2-24.4). Median disease-free survival (DFS) in 81 patients undergoing resection was 12.3 months (95% CI 9.7-23.1). The median OS from start of palliative CTX (OSpall) was 10.9 months (95% 9.4-14.6). A combined Systemic Inflammatory Score (SIS) comprising all evaluated SIR markers correlated significantly with ORR, PFS, and OSpall. Patients with a high SIS (≥ 2) vs. SIS 0 had a significantly inferior OSpall (HR 8.7 95% CI 3.71-20.38, p < 0.001). Multivariate analysis including known prognostic markers (ECOG, CA19-9, LDH, and N- and M-status) identified the SIS as an independent prognostic factor. CONCLUSIONS: Inflammatory markers associate with inferior survival outcomes in patients with iCCA. A simple SIS may guide treatment decisions in patients treated with systemic chemotherapy.

Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receiving palliative chemotherapy.

PURPOSE: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. METHODS: A cohort of 193 PDAC patients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. RESULTS: All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802-6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). CONCLUSION: Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.

Long-term outcome of patients with advanced pancreatic cancer treated with sequential chemotherapies before the era of modern combination therapy protocols.

INTRODUCTION: Patients (pts) with locally advanced (LAPC) or metastatic pancreatic ductal adenocarcinoma (mPDAC) have a dismal prognosis. Recently, new combination chemotherapies such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated superiority over gemcitabine monotherapy. However, a substantial proportion of pts cannot tolerate these intensive front-line protocols. Moreover, the long-term superiority of multiagent protocols over less intensive strategies remains to be shown. To provide a benchmark for future studies, we analyzed the outcome of patients with LAPC or mPDAC treated at the West German Cancer Center before the FOLFIRINOX/nab-paclitaxel + gemcitabine era. METHODS: This retrospective analysis included 201 consecutive pts with LAPC and mPDAC treated between 2007 and 2011. Efficacy parameters were correlated with type of chemotherapy, number of treatment lines and clinicopathological parameters. RESULTS: Gemcitabine monotherapy was given as first-line therapy in 51.1%, whereas 48.9% received combination chemotherapies such as gemcitabine/oxaliplatin or FOLFOX. Patients received a median of two lines of treatment, with 54.8% receiving second-line and 37.9% receiving third- and further-line therapies. There was no significant difference between gemcitabine monotherapy and combination therapies. Despite moderate activity of first-line treatment, median overall survival for LAPC was 11.3 months and 8.7 months for mPDAC. Multivariate analysis identified age and number of treatment lines as prognostic markers. CONCLUSION: The long-term outcome of unselected pts with LAPC and mPDAC treated before the introduction of aggressive multiagent chemotherapy protocols compares favorably with the results of contemporary benchmark trials. This suggests a multifactorial benefit from interdisciplinary care provided over sequential treatment lines at high volume expert centers.

Maternal relationship analysis of skeletal remains from Early Medieval cemetery in Slovakia.

SUMMARY: MtDNA from the skeletal remains of two bodies buried in the grave No. F44 from Nitra-Sindolka (woman and child) was analysed. Cemeteries in Sindolka belong to the Bijelo Brdo culture, where Slavs and Magyars were buried in the 10th - 11th centuries. Surprisingly, the analysis of mtDNA has shown no maternal relationship between buried persons, since the woman belongs to haplogroup T1a and the child to haplogroup J. Since both haplogroups can be found in Near Eastern and European populations at similar frequencies, the tested samples from the tomb No. F44 cannot be clearly assigned to ethnic origin.

Y-chromosome analysis of ancient Hungarian and two modern Hungarian-speaking populations from the Carpathian Basin.

The Hungarian population belongs linguistically to the Finno-Ugric branch of the Uralic family. The Tat C allele is an interesting marker in the Finno-Ugric context, distributed in all the Finno-Ugric-speaking populations, except for Hungarians. This question arises whether the ancestral Hungarians, who settled in the Carpathian Basin, harbored this polymorphism or not. 100 men from modern Hungary, 97 Szeklers (a Hungarian-speaking population from Transylvania), and 4 archaeologically Hungarian bone samples from the 10(th) century were studied for this polymorphism. Among the modern individuals, only one Szekler carries the Tat C allele, whereas out of the four skeletal remains, two possess the allele. The latter finding, even allowing for the low sample number, appears to indicate a Siberian lineage of the invading Hungarians, which later has largely disappeared. The two modern Hungarian-speaking populations, based on 22 Y-chromosomal binary markers, share similar components described for other Europeans, except for the presence of the haplogroup P*(xM173) in Szekler samples, which may reflect a Central Asian connection, and high frequency of haplogroup J in both Szeklers and Hungarians. MDS analysis based on haplogroup frequency values, confirms that modern Hungarian and Szekler populations are genetically closely related, and similar to populations from Central Europe and the Balkans.

The relevance of placental location at 20-23 gestational weeks for prediction of placenta previa at delivery: evaluation of 8650 cases.

OBJECTIVE: To determine the correlation between placental position at 20-23 weeks and incidence of birth complications caused by placental position. SUBJECTS AND METHODS: In an ongoing prospective study, placental position was determined by transabdominal sonography as part of anomaly scanning at 20-23 gestational weeks, followed by transvaginal sonography in uncertain or suspicious situations. Examination was performed in 9532 cases; feedback was obtained from 8650 patients (90.7%). RESULTS: Transabdominal sonography was followed by transvaginal scan in 363 of 8650 cases (4.2%). In 8551 cases (98.9%), we found normal placental position, with the placenta not reaching the internal os and a Cesarean section rate of 17.1% (1458/8551). The incidence of 'low placental position', with the placenta reaching the internal os was 0.66% (57/8650), with a Cesarean section rate of 21% (12/57). In 0.49% (42/8650) of cases, the placenta overlapped the internal os at 20-23 weeks; Cesarean section because of placenta previa or bleeding was performed in 28 of 8650 cases (0.32%). Vaginal delivery was possible in 43% of cases (13/30), when the overlap did not exceed 25 mm. If the overlap exceeded 25 mm (12 cases), no vaginal delivery was reported. There was no reported case of placenta previa missed at the 20-23-week scan. CONCLUSION: At 20-23 weeks, a combination of routine transabdominal and indication-based transvaginal location of placental position is a powerful tool in predicting placenta previa at delivery. The advantage of determining placental position at this stage of pregnancy is a low false-positive rate compared to at earlier stages of pregnancy. We conclude that an overlapping placenta at 20-23 weeks has the consequence of a high probability of placenta previa at delivery. An overlap of 25 mm or more at 20-23 weeks seems to be incompatible with later vaginal delivery.

Sonographic markers of exencephaly at 9 + 3 weeks of gestation.

Following the introduction of transvaginal sonography, several first trimester diagnoses of the exencephaly anencephaly sequence have been reported, with the earliest being described at 10 weeks of gestation. We report a case with a high index of suspicion for exencephaly at 9 weeks and 3 days because of three sonographic features: the cranial pole of the embryo was smaller than the chest, the cranial pole bulged dorsally and the surface of the cranium was irregular. The diagnosis was confirmed by a repeat ultrasound examination at 11 + 4 weeks and by autopsy after termination of pregnancy.

[Bacteriologic findings before and in transcervical chorionic villi biopsy and their clinical relevance]. / Bakteriologische Befunde vor und bei transzervikaler Chorionzottenbiopsie und deren klinische Relevanz.

Between August 1987 and May 1989, bacteriological examinations of smears from the cervical canal was performed in 358 pregnant women, who underwent transcervical sampling of chorionic villi. The outcome of 349 of these pregnancies is documented. 12 of these patients (3.5%) had an artificial abortion for genetic reasons. In 12 other patients, the pregnancy ended before 28 weeks (one child surviving). Microbiological examinations showed that in 187 women (52%), it was possible to culture one or more microorganisms from the cervical canal. The most frequently detected pathogen was Chlamydia trachomatis (111 women, 31%). In pregnancies, where more than one microorganism could be cultured, the risk of following abortion was 8.9 times higher than in those, where no pathogens could be found. In only two of the 12 women with a subsequent spontaneous abortion (16.6%), no microorganism could be found. The bacterial contamination of the cervical canal during TC-CVS seems to be a risk factor for subsequent abortion. Therefore, a bacteriological examination of cervical flora should be performed before as well as during TC-CVS, and antibiotic therapy should be initiated in case of positive results.

[Hypotrichosis congenita hereditaria Marie Unna with Ehlers-Danlos syndrome and atopy]. / Hypotrichosis congenita hereditaria Marie Unna mit Ehlers-Danlos-Syndrom und Atopie.

A family suffering from hypotrichosis congenita hereditaria Marie Unna is reported (16 members affected in five generations). The typical symptoms of this autosomal dominant syndrome were found: pili torti, canaliculi et trianguli, inborn generalized hypotrichosis, later on resulting in alopecia of the androgenetic type. A 19-year-old female patient with hyperandrogenemia was treated with cyproterone acetate and ethinyl estradiol. Furthermore, hypotrichosis was associated with Ehlers-Danlos syndrome and atopic symptoms in the last three generations of the family. There does not seem to be any genetic connection between the syndromes however.

[Treatment of keloids by cryotherapy]. / Keloidbehandlung mittels Kryotherapie.

Cryotherapy was performed on 7 patients with 35 keloids of different pathogenesis. In 5 out of these patients, prior treatment with creams, radiotherapy, or excision followed by radiotherapy had failed. The keloids were frozen several times by contact with liquid nitrogen (40 to 90 sec). After bullous local reactions and crusted healing, the lesions gradually leveled down. Atrophic scars resulted after 1 to 8 treatments. Old keloids (2 to 8-year-old) showed good therapeutic response. No relapses were registered during the follow-up period of 3 month up to a year. Only one patient discontinued therapy, and a 10-year-old boy could not stand the initial pain of freezing. On account of our encouraging results and the low complication rate, we recommend cryotherapy in the treatment of old keloids.

[Failure to form wrinkles on the finger tips in the warm water test in lepromatous nerve damage]. / Fehlende Faltenbildung der Fingerkuppen im Warmwassertest bei lepromatöser Nervenschädigung.

In order to estimate the extent of nerval defects, we recommend the soaking test which may reveal affected areas indicated by the loss of wrinkling at the finger-tips after soaking the hands in warm water for half an hour. Thus we found impairment in the formation of wrinkles in 6 out of 7 tested patients suffering from different types of leprosy. In order to study the significance of the soaking test with regard to acute nerval signs and symptoms, one patient was reexaminated when he showed acute painful swelling of the right n. ulnaris. There was normal wrinkling observed at the affected hand, which did not differ from the outcome of the preceding test. This finding indicates that the soaking test is only appropriate to the examination of chronic nerval lesions in leprosy.

[Osteitis leprosa multiplex cystica--an early symptom of lepromatous leprosy]. / Ostitis leprosa multiplex cystica--ein Frühsymptom der lepromatösen Lepra.

Bone lesions of the finger in a 20-year-old leprosy patient are described to show their diagnostic value. The aetiological differences between specific (caused by Mycobacterium leprae itself) and unspecific osseal changes are morphologically noticeable in morbus Hansen. The X-ray picture shows cystic lightening by granulomatous destruction and distal absorption of the bone. These lesions are typical, and radiological investigations might be the first step in the diagnosis of leprosy. In our case, ostitis leprosa multiplex cystica, an early, specific bone lesion, was predominant.

[Bone changes in Hansen's disease]. / Knochenveränderungen bei Morbus Hansen.

Bone lesion is a frequent organic manifestation in leprosy. Osseal destructions caused by granulomatous process induced by M. leprae are so-called specific lesions in contrast to non-specific lesions based on nerval or arterial diseases. The specific osseal alterations are characterized by cystic brightenings in roentgenograms while non-specific osseal changes show absorption to bone structure as akroosterolysis and osteoporosis. Typical radiologic findings in different stages of mutilation are demonstrated.